39 results
Sex-dependent differences in vulnerability to early risk factors for posttraumatic stress disorder: results from the AURORA study
- Stephanie Haering, Antonia V. Seligowski, Sarah D. Linnstaedt, Vasiliki Michopoulos, Stacey L. House, Francesca L. Beaudoin, Xinming An, Thomas C. Neylan, Gari D. Clifford, Laura T. Germine, Scott L. Rauch, John P. Haran, Alan B. Storrow, Christopher Lewandowski, Paul I. Musey, Jr., Phyllis L. Hendry, Sophia Sheikh, Christopher W. Jones, Brittany E. Punches, Robert A. Swor, Nina T. Gentile, Lauren A. Hudak, Jose L. Pascual, Mark J. Seamon, Claire Pearson, David A. Peak, Roland C. Merchant, Robert M. Domeier, Niels K. Rathlev, Brian J. O'Neil, Leon D. Sanchez, Steven E. Bruce, Steven E. Harte, Samuel A. McLean, Ronald C. Kessler, Karestan C. Koenen, Jennifer S. Stevens, Abigail Powers
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- Journal:
- Psychological Medicine , First View
- Published online by Cambridge University Press:
- 22 May 2024, pp. 1-11
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Background
Knowledge of sex differences in risk factors for posttraumatic stress disorder (PTSD) can contribute to the development of refined preventive interventions. Therefore, the aim of this study was to examine if women and men differ in their vulnerability to risk factors for PTSD.
MethodsAs part of the longitudinal AURORA study, 2924 patients seeking emergency department (ED) treatment in the acute aftermath of trauma provided self-report assessments of pre- peri- and post-traumatic risk factors, as well as 3-month PTSD severity. We systematically examined sex-dependent effects of 16 risk factors that have previously been hypothesized to show different associations with PTSD severity in women and men.
ResultsWomen reported higher PTSD severity at 3-months post-trauma. Z-score comparisons indicated that for five of the 16 examined risk factors the association with 3-month PTSD severity was stronger in men than in women. In multivariable models, interaction effects with sex were observed for pre-traumatic anxiety symptoms, and acute dissociative symptoms; both showed stronger associations with PTSD in men than in women. Subgroup analyses suggested trauma type-conditional effects.
ConclusionsOur findings indicate mechanisms to which men might be particularly vulnerable, demonstrating that known PTSD risk factors might behave differently in women and men. Analyses did not identify any risk factors to which women were more vulnerable than men, pointing toward further mechanisms to explain women's higher PTSD risk. Our study illustrates the need for a more systematic examination of sex differences in contributors to PTSD severity after trauma, which may inform refined preventive interventions.
443 Treatment experience and symptom burden in multiple myeloma: interim results of a longitudinal electronic patient-reported outcomes study
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- Mihir Patel, Anneli Nina, Brenda Branchaud, David Campbell, Kris Herring, Thomas LeBlanc
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- Journal:
- Journal of Clinical and Translational Science / Volume 8 / Issue s1 / April 2024
- Published online by Cambridge University Press:
- 03 April 2024, pp. 131-132
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OBJECTIVES/GOALS: Patients with multiple myeloma (MM) experience significant disease- and treatment-related symptom burden, especially with higher lines of therapy (LOT). We used a remote symptom monitoring app to characterize overall symptom profile, symptom bother, and quality of life (QOL) among patients with MM across LOT and longitudinally. METHODS/STUDY POPULATION: We used Carevive PROmpt, a symptom monitoring app for cancer patients. From 11/10/22 to 9/27/23, we enrolled 84 adult patients with MM of any stage and anywhere in the treatment continuum from Duke Health MM clinics. Participants received weekly symptom surveys while on active treatment. Per prior studies, we defined heavily pretreated patients as those on current LOT ≥4. Our sample had a mean (SD) age of 63.7 (10.8) years and was 56.0% male; 73.8% had a prior bone marrow transplant, 40.5% were on LOT ≥4 (53.6% on LOT <4, 6.0% missing), 58.3% were on triplet therapy or higher. For 14 symptoms, we described the prevalence of moderate to very severe (MOD-VS) symptoms based on LOT overall and over time. We also described responses to “How bothersome are treatment side effects?” and “Overall QOL over the past week” based on LOT. RESULTS/ANTICIPATED RESULTS: Surveys continued for a mean (SD) of 14.9 (9.6) weeks (range: 44). The top 5 MOD-VS symptoms ever experienced were fatigue (66.7% of patients), neuropathy (48.8%), muscle pain (44.0%), insomnia (39.3%), and general pain (38.1%). Patients on LOT ≥4 had most of these symptoms more often than LOT <4 (fatigue: 70.6% of patients vs. 60.0%, neuropathy: 71.8% vs. 40.0%, muscle pain: 47.1% vs. 42.2%, insomnia: 35.3% vs. 40.0%, general pain: 47.1% vs. 33.3%). For those on LOT ≥4, 42.9% of survey responses endorsed “somewhat”, “quite a bit”, or “very much” symptom bother compared to 32.7% for LOT <4. QOL was similar between groups. Over many months, patients on LOT ≥4 had several persistent symptoms (neuropathy, sadness, insomnia), but even those on LOT <4 had unmet symptom needs (fatigue, general pain, constipation). DISCUSSION/SIGNIFICANCE: Evidence shows that treatment selection at higher LOT in MM often underrates the impact of cumulative symptom burden. Our study reveals significant longitudinal unmet needs regarding symptom and distress management in MM; understanding this can help guide treatment decisions and palliative care for MM patients with escalating treatment demands.
32 Influence of Prior Experience with Computer-Based Technology on Tablet-Based Neurocognitive Test Performance: Data from a sample of cognitively impaired South African older adults
- Nina S Steenkamp, Hetta-Mari Gouse, Rhiannon Changuion, Christopher M Ferraris, Daphne Tsapalas, Nana Asiedu, Anthony F Santoro, Kevin G. F. Thomas, Reuben N Robbins
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- Journal:
- Journal of the International Neuropsychological Society / Volume 29 / Issue s1 / November 2023
- Published online by Cambridge University Press:
- 21 December 2023, pp. 713-714
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Objective:
The global prevalence of persons living with dementia will soon exceed 50 million. Most of these individuals reside in low- and middle-income countries (LMICs). In South Africa, one such LMIC, the physician-to-patient ratio of 9:10 000 severely limits the capacity of clinicians to screen, assess, diagnose, and treat dementias. One way to address this limitation is by using mobile health (mHealth) platforms to scale-up neurocognitive testing. In this paper, we describe one such platform, a brief tablet-based cognitive assessment tool (NeuroScreen) that can be administered by lay health-providers. It may help identify patients with cognitive impairment (related, for instance, to dementia) and thereby improve clinical care and outcomes. However, there is a lack of data regarding (a) the acceptability of this novel technology for delivery of neurocognitive assessments in LMIC-resident older adults, and (b) the influence of technology-use experience on NeuroScreen performance of LMIC-resident older adults. This study aimed to fill that knowledge gap, using a sample of cognitively impaired South African older adults.
Participants and Methods:Participants were 60 older adults (63.33% female; 91.67% right-handed; age M = 68.90 years, SD = 9.42, range = 50-83), all recruited from geriatric and memory clinics in Cape Town, South Africa. In a single 1-hour session, they completed the entire NeuroScreen battery (Trail Making, Number Speed, Finger Tapping, Visual Discrimination, Number Span Forward, Number Span Backward, List Learning, List Recall) as well as a study-specific questionnaire assessing acceptability of NeuroScreen use and overall experience and comfort with computer-based technology. We summed across 11 questionnaire items to derive a single variable capturing technology-use experience, with higher scores indicating more experience.
Results:Almost all participants (93.33%) indicated that NeuroScreen was easy to use. A similar number (90.00%) indicated they would be comfortable completing NeuroScreen at routine doctor's visits. Only 6.67% reported feeling uncomfortable using a tablet, despite about three-quarters (76.67%) reporting never having used a tablet with a touchscreen before. Almost one in five participants (18.33%) reported owning a computer, 10.00% a tablet, and 70.00% a smartphone. Correlations between test performance and technology-use experience were statistically significant (or strongly tended toward significance) for most NeuroScreen subtests that assessed higherorder cognitive functioning and that required the participant to manipulate the tablet themselves: Trail Making 2 (a measure of cognitive switching ability), r = .24, p = .05; Visual Discrimination A (complex processing speed [number-symbol matching]), r = .38, p = .002; Visual Discrimination B (pattern recognition), r = .37, p = .004; Number Speed (simple information processing speed), r = .36, p = .004. For the most part, there were no such significant associations when the NeuroScreen subtest required only verbal input from the participant (i.e., on the list learning and number span tasks).
Conclusions:NeuroScreen, a tablet-based neurocognitive screening tool, appears feasible for use among older South Africans, even if they are cognitively impaired and have limited technological familiarity. However, test performance might be influenced by amount of technology-use experience; clinicians using the battery must consider this in their interpretations.
82 Behavioral, Emotional, and Adaptive Functioning in a Pediatric anti-NMDARE Population
- Madeline R King, Marie C McGrath, Ashley Higgins, Nina Hattiangadi Thomas
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- Journal of the International Neuropsychological Society / Volume 29 / Issue s1 / November 2023
- Published online by Cambridge University Press:
- 21 December 2023, pp. 74-75
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Objective:
Anti-N-methyl-D-aspartate receptor encephalitis (anti-NMDARE) is a complex, yet treatable autoimmune disorder characterized by a fairly abrupt onset of a constellation of symptoms attributable to diffuse brain dysfunction (Tarantino et al., 2021). Despite the potential for a severe disease course, most patients have a favorable outcome with substantial recovery (Dalmau et al., 2011; Titulaer et al., 2013). Nevertheless, there is limited literature discussing the long-term outcomes in patients with anti-NMDARE, particularly in pediatric patients. The primary objective of this study is to examine and describe behavioral, emotional, adaptive, and executive functioning outcomes in pediatric and young adult patients with this disease. This study also sought to provide information on the perceived health-related quality of life (HRQoL) of patients and their parents and investigate the impact of anti-NMDARE on parents and family functioning.
Participants and Methods:All individuals known to have been diagnosed and treated for anti-NMDARE at The Children’s Hospital of Philadelphia (CHOP) between January 1, 2005, and October 1, 2020, were contacted with both patients and their parents/guardians invited to participate. Eighteen pediatric patients between the ages of 6 and 26 and/or their parents/caregivers participated in the study. Of the 18 patients represented in the sample, 50% were white/Caucasian, and 67% were female. The mean duration of time since symptom onset was 7.1 years. Primary outcomes were measured through standardized questionnaires of emotional, behavioral, and adaptive functioning (BASC-3) and executive functioning (BRIEF2 or BRIEF-A). Secondary outcomes related to family functioning and HRQoL were measured through (PedsQL™ and PedsQL™ Family Impact Module.)
Results:All aggregate T-scores for the BASC and BRIEF placed children with anti-NMDARE within an age-appropriate range regarding behavioral, emotional, adaptive, and executive functioning outcomes. Children with anti-NMDARE were not found to have lower HRQoL compared to their healthy same-age peers. Moreover, parents of children with anti-NMDARE did not endorse a prolonged impact of this illness on family functioning and adjustment.
Conclusions:This study aimed to better understand the neurobehavioral profile and the long-term outcomes of children diagnosed with anti-NMDARE, with the ultimate goal of advancing understanding of this encephalitis. Consistent with findings from several reviewed studies on long-term follow-up, the present study suggests that most children with a history of anti-NMDARE show good functional recovery over time. However, data on the neurobehavioral sequelae, quality of life, and adaptive behavior in patients diagnosed with anti-NMDARE are still sparse, especially at pediatric age. In order to understand and learn to manage the needs of patients with anti-NMDARE, particularly regarding the impact this disease can have on daily life and school performance, additional neuropsychological research involving larger samples, longitudinal studies, and increased methodological consistency is required.
55 The Neurocognitive Profile of a Child with Rubinstein-Taybi Syndrome (RSTS-Type 2)
- Rachel Canella, Nina Hattiangadi Thomas
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- Journal:
- Journal of the International Neuropsychological Society / Volume 29 / Issue s1 / November 2023
- Published online by Cambridge University Press:
- 21 December 2023, pp. 660-661
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Objective:
Rubinstein-Taybi Syndrome (RSTS) is a rare multiple congenital autosomal dominant disorder, with an incidence of roughly 1/125,000 live births (Milani et al., 2015). RSTS is characterized by several typical somatic characteristics and developmental disabilities. Common neurological findings in patients with RSTS include mild or moderate intellectual impairment and delays in gross motor development (Taupiac et al., 2021; Hamilton et al., 2016). Additional characteristics observed among individuals with RSTS include hyperactivity, abnormalities in expressive language, inattention, motor difficulties, noise intolerance, maladaptive behaviors, and fewer modes of communication (Waite et al., 2015). Due to the condition’s rarity, very few studies have investigated the cognitive profiles of RSTS patients with clinical features of EP300 (Type 2; Morel et al., 2018) in effected youth. This case study represents the first reported comprehensive neuropsychological description to our knowledge of an individual with this condition.
Participants and Methods:Participant: The participant is an 8-year, 4-month-old young girl referred for neuropsychological evaluation. LX was diagnosed with failure to thrive due to her small size, although she met all developmental milestones on time. LX was diagnosed with RSTS, Type 2 through genetic testing and blood work following concerns about small stature, microcephaly discovered on an MRI, and feeding difficulties. A 4kb deletion of 22q13.2 which contains exon 2 of EP300 was identified. Method: Medical and school records review, a clinical interview with LX and her family, neuropsychological assessment, and parent-and teacher-report questionnaires were used to assess functioning. Raw scores were standardized for comparison against age- and (where appropriate) gender-matched peers.
Results:In addition to her medical diagnoses of RSTS, Type 2, and her prior diagnosis of ADHD - Combined Subtype, LX also met diagnostic criteria for Specific Learning Disability with Impairment in Reading and a Mixed Receptive-Expressive Language Disorder. LX also met criteria for Encephalopathy as characterized by weakness in visual perception, visuospatial judgment and reasoning, and working memory. LX demonstrated adaptive functioning weaknesses in domains such as self-direction, and self-care, while communication skills were reported to be average. Overall, LX’s current levels of general cognitive ability and adaptive functioning were consistent with Borderline Intellectual Functioning; however, the diagnosis was deferred at present. Parents and teachers reported difficulties with peer relationships, hyperactivity, and aggression, consistent with known features of this condition. Strengths were noted in verbal and nonverbal reasoning, spelling, math calculation, verbal and visual memory, and improvement in attention with medication, which all fell within the broadly average range of functioning.
Conclusions:LX’s presentation and pattern of neuropsychological findings are consistent with the current conceptualization of development in RSTS, Type 2, but reflect a more nuanced clinical picture. In particular, although general cognitive ability was borderline overall, deficits were largely circumscribed to spatial reasoning, with broadly average verbal and nonverbal reasoning abilities. This case highlights the importance of comprehensive neuropsychological testing of patients with RSTS. Reporting of general cognitive ability scores alone may obscure underlying patterns of relative strengths and weaknesses that have important ramifications for both targeted interventions and for a more positive prognosis related to functioning in academic, home, and community environments.
50 The Neuropsychological Profile of S/A/3A-Related Disorder/Witteveen-Kolk Syndrome: A Case Study
- Anthony R Gioia, Nina H Thomas
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- Journal:
- Journal of the International Neuropsychological Society / Volume 29 / Issue s1 / November 2023
- Published online by Cambridge University Press:
- 21 December 2023, pp. 656-657
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Objective:
The SIN3A gene mutation is a rare genetic mutation with few reported cases (< 1 in 1,000,000) associated with autosomal dominant Witteveen-Kolk Syndrome, a rare neurodevelopmental syndrome only discussed in the past decade (Witteveen et al., 2016). This syndrome can be characterized by short stature, distinctive facial features, developmental delay, mild intellectual disability, autism spectrum disorder, hypotonia, and seizures (Balasubramanian et al., 2021), however a paucity of information regarding comprehensive neuropsychological functioning in these individuals is present in the literature, and even this recent review study noted that intellectual ability was rarely assessed through formal testing (6 of 28 cases). We present a case, “M”, to help describe a potential pattern of neurocognitive strengths and weaknesses in this population.
Participants and Methods:The participant, “M”, was diagnosed with a de novo mutation in the SIN3A gene at the age of 11 years with previous diagnoses of global developmental delay, hypotonia, autism spectrum disorder, specific learning disability in mathematics, developmental coordination disorder, and attention deficit hyperactivity disorder. M was seen for a comprehensive neuropsychological evaluation at 11 years of age at an academic medical center, which consisted of comprehensive review of medical and school records, parent and child interview, questionnaires, and performance-based testing.
Results:M’s verbal and language skills emerged as a particular strength. Her verbal memory, verbal fluency, and verbal comprehension skills were all in the average range or above, as were reading, reading comprehension, and spelling skills. M demonstrated a pattern of notable weaknesses in visuospatial skills, including impaired visuospatial reasoning, visuomotor integration, visual scanning, visual perception, and visual memory. Additionally, M demonstrated a slight weakness in Low Average mathematics skills. M also demonstrated fine motor impairment with impaired speed, coordination, and accuracy. Although immediate auditory attention was noted to be average, performance on a test of sustained attention indicated a moderate persistence of attention concerns. Likewise, M’s mother reported her to be very elevated on symptoms of both attention and hyperactivity/impulsivity. Finally, M’s mother reported elevated concerns related to M’s peer relations and atypical behaviors and below average adaptive skills.
Conclusions:Due to the rarity of M’s de novo mutation in the SIN3A gene, M’s pattern of weaknesses in visuospatial skills, fine motor skills, attention/executive functioning, and social skills, as well as her strengths in verbal skills can aid in further understanding the pattern of cognitive strengths and weaknesses in children with a mutation in the SIN3A gene. Additionally, given her mild weaknesses in math skills, it is possible that M’s performance on mathematics assessments may be impacted by her visuospatial weakness and thus better conceptualized as a visuospatial issue rather than a learning disability. Overall, this case can aid in identifying specific cognitive risk factors, such as visuospatial skills, in this population and lead to more targeted assessment and intervention, and highlights the importance of more nuanced cognitive evaluation as reporting of a general cognitive ability score alone may obscure underlying patterns of cognitive strength and weakness.
Childhood trauma moderates schizotypy-related brain morphology: analyses of 1182 healthy individuals from the ENIGMA schizotypy working group
- Yann Quidé, Oliver J. Watkeys, Emiliana Tonini, Dominik Grotegerd, Udo Dannlowski, Igor Nenadić, Tilo Kircher, Axel Krug, Tim Hahn, Susanne Meinert, Janik Goltermann, Marius Gruber, Frederike Stein, Katharina Brosch, Adrian Wroblewski, Florian Thomas-Odenthal, Paula Usemann, Benjamin Straube, Nina Alexander, Elisabeth J. Leehr, Jochen Bauer, Nils R. Winter, Lukas Fisch, Katharina Dohm, Wulf Rössler, Lukasz Smigielski, Pamela DeRosse, Ashley Moyett, Josselin Houenou, Marion Leboyer, James Gilleen, Sophia I. Thomopoulos, Paul M. Thompson, André Aleman, Gemma Modinos, Melissa J. Green
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- Psychological Medicine / Volume 54 / Issue 6 / April 2024
- Published online by Cambridge University Press:
- 20 October 2023, pp. 1215-1227
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Background
Schizotypy represents an index of psychosis-proneness in the general population, often associated with childhood trauma exposure. Both schizotypy and childhood trauma are linked to structural brain alterations, and it is possible that trauma exposure moderates the extent of brain morphological differences associated with schizotypy.
MethodsWe addressed this question using data from a total of 1182 healthy adults (age range: 18–65 years old, 647 females/535 males), pooled from nine sites worldwide, contributing to the Enhancing NeuroImaging Genetics through Meta-Analysis (ENIGMA) Schizotypy working group. All participants completed both the Schizotypal Personality Questionnaire Brief version (SPQ-B), and the Childhood Trauma Questionnaire (CTQ), and underwent a 3D T1-weighted brain MRI scan from which regional indices of subcortical gray matter volume and cortical thickness were determined.
ResultsA series of multiple linear regressions revealed that differences in cortical thickness in four regions-of-interest were significantly associated with interactions between schizotypy and trauma; subsequent moderation analyses indicated that increasing levels of schizotypy were associated with thicker left caudal anterior cingulate gyrus, right middle temporal gyrus and insula, and thinner left caudal middle frontal gyrus, in people exposed to higher (but not low or average) levels of childhood trauma. This was found in the context of morphological changes directly associated with increasing levels of schizotypy or increasing levels of childhood trauma exposure.
ConclusionsThese results suggest that alterations in brain regions critical for higher cognitive and integrative processes that are associated with schizotypy may be enhanced in individuals exposed to high levels of trauma.
Synchrotron Radiation and Laser Light Microscopy Partnership for the Study of Biological Systems: The Case of Soft X-ray Tomography and Structured Illumination Microscopy at Cryogenic Temperatures
- Maria Harkiolaki, Nina Vyas, Claire Pizzey, Thomas Fish, Archana Jadhav, Kamal Nahas, Chidinma Okolo
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- Microscopy and Microanalysis / Volume 28 / Issue S1 / August 2022
- Published online by Cambridge University Press:
- 22 July 2022, pp. 1328-1330
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- August 2022
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Using polygenic scores and clinical data for bipolar disorder patient stratification and lithium response prediction: machine learning approach – CORRIGENDUM
- Micah Cearns, Azmeraw T. Amare, Klaus Oliver Schubert, Anbupalam Thalamuthu, Joseph Frank, Fabian Streit, Mazda Adli, Nirmala Akula, Kazufumi Akiyama, Raffaella Ardau, Bárbara Arias, JeanMichel Aubry, Lena Backlund, Abesh Kumar Bhattacharjee, Frank Bellivier, Antonio Benabarre, Susanne Bengesser, Joanna M. Biernacka, Armin Birner, Clara Brichant-Petitjean, Pablo Cervantes, HsiChung Chen, Caterina Chillotti, Sven Cichon, Cristiana Cruceanu, Piotr M. Czerski, Nina Dalkner, Alexandre Dayer, Franziska Degenhardt, Maria Del Zompo, J. Raymond DePaulo, Bruno Étain, Peter Falkai, Andreas J. Forstner, Louise Frisen, Mark A. Frye, Janice M. Fullerton, Sébastien Gard, Julie S. Garnham, Fernando S. Goes, Maria Grigoroiu-Serbanescu, Paul Grof, Ryota Hashimoto, Joanna Hauser, Urs Heilbronner, Stefan Herms, Per Hoffmann, Andrea Hofmann, Liping Hou, Yi-Hsiang Hsu, Stephane Jamain, Esther Jiménez, Jean-Pierre Kahn, Layla Kassem, Po-Hsiu Kuo, Tadafumi Kato, John Kelsoe, Sarah Kittel-Schneider, Sebastian Kliwicki, Barbara König, Ichiro Kusumi, Gonzalo Laje, Mikael Landén, Catharina Lavebratt, Marion Leboyer, Susan G. Leckband, Mario Maj, the Major Depressive Disorder Working Group of the Psychiatric Genomics Consortium, Mirko Manchia, Lina Martinsson, Michael J. McCarthy, Susan McElroy, Francesc Colom, Marina Mitjans, Francis M. Mondimore, Palmiero Monteleone, Caroline M. Nievergelt, Markus M. Nöthen, Tomas Novák, Claire O'Donovan, Norio Ozaki, Vincent Millischer, Sergi Papiol, Andrea Pfennig, Claudia Pisanu, James B. Potash, Andreas Reif, Eva Reininghaus, Guy A. Rouleau, Janusz K. Rybakowski, Martin Schalling, Peter R. Schofield, Barbara W. Schweizer, Giovanni Severino, Tatyana Shekhtman, Paul D. Shilling, Katzutaka Shimoda, Christian Simhandl, Claire M. Slaney, Alessio Squassina, Thomas Stamm, Pavla Stopkova, Fasil TekolaAyele, Alfonso Tortorella, Gustavo Turecki, Julia Veeh, Eduard Vieta, Stephanie H. Witt, Gloria Roberts, Peter P. Zandi, Martin Alda, Michael Bauer, Francis J. McMahon, Philip B. Mitchell, Thomas G. Schulze, Marcella Rietschel, Scott R. Clark, Bernhard T. Baune
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- Journal:
- The British Journal of Psychiatry / Volume 221 / Issue 2 / August 2022
- Published online by Cambridge University Press:
- 04 May 2022, p. 494
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- August 2022
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Using polygenic scores and clinical data for bipolar disorder patient stratification and lithium response prediction: machine learning approach
- Micah Cearns, Azmeraw T. Amare, Klaus Oliver Schubert, Anbupalam Thalamuthu, Joseph Frank, Fabian Streit, Mazda Adli, Nirmala Akula, Kazufumi Akiyama, Raffaella Ardau, Bárbara Arias, Jean-Michel Aubry, Lena Backlund, Abesh Kumar Bhattacharjee, Frank Bellivier, Antonio Benabarre, Susanne Bengesser, Joanna M. Biernacka, Armin Birner, Clara Brichant-Petitjean, Pablo Cervantes, Hsi-Chung Chen, Caterina Chillotti, Sven Cichon, Cristiana Cruceanu, Piotr M. Czerski, Nina Dalkner, Alexandre Dayer, Franziska Degenhardt, Maria Del Zompo, J. Raymond DePaulo, Bruno Étain, Peter Falkai, Andreas J. Forstner, Louise Frisen, Mark A. Frye, Janice M. Fullerton, Sébastien Gard, Julie S. Garnham, Fernando S. Goes, Maria Grigoroiu-Serbanescu, Paul Grof, Ryota Hashimoto, Joanna Hauser, Urs Heilbronner, Stefan Herms, Per Hoffmann, Andrea Hofmann, Liping Hou, Yi-Hsiang Hsu, Stephane Jamain, Esther Jiménez, Jean-Pierre Kahn, Layla Kassem, Po-Hsiu Kuo, Tadafumi Kato, John Kelsoe, Sarah Kittel-Schneider, Sebastian Kliwicki, Barbara König, Ichiro Kusumi, Gonzalo Laje, Mikael Landén, Catharina Lavebratt, Marion Leboyer, Susan G. Leckband, Mario Maj, the Major Depressive Disorder Working Group of the Psychiatric Genomics Consortium, Mirko Manchia, Lina Martinsson, Michael J. McCarthy, Susan McElroy, Francesc Colom, Marina Mitjans, Francis M. Mondimore, Palmiero Monteleone, Caroline M. Nievergelt, Markus M. Nöthen, Tomas Novák, Claire O'Donovan, Norio Ozaki, Vincent Millischer, Sergi Papiol, Andrea Pfennig, Claudia Pisanu, James B. Potash, Andreas Reif, Eva Reininghaus, Guy A. Rouleau, Janusz K. Rybakowski, Martin Schalling, Peter R. Schofield, Barbara W. Schweizer, Giovanni Severino, Tatyana Shekhtman, Paul D. Shilling, Katzutaka Shimoda, Christian Simhandl, Claire M. Slaney, Alessio Squassina, Thomas Stamm, Pavla Stopkova, Fasil Tekola-Ayele, Alfonso Tortorella, Gustavo Turecki, Julia Veeh, Eduard Vieta, Stephanie H. Witt, Gloria Roberts, Peter P. Zandi, Martin Alda, Michael Bauer, Francis J. McMahon, Philip B. Mitchell, Thomas G. Schulze, Marcella Rietschel, Scott R. Clark, Bernhard T. Baune
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- Journal:
- The British Journal of Psychiatry / Volume 220 / Issue 4 / April 2022
- Published online by Cambridge University Press:
- 28 February 2022, pp. 219-228
- Print publication:
- April 2022
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Background
Response to lithium in patients with bipolar disorder is associated with clinical and transdiagnostic genetic factors. The predictive combination of these variables might help clinicians better predict which patients will respond to lithium treatment.
AimsTo use a combination of transdiagnostic genetic and clinical factors to predict lithium response in patients with bipolar disorder.
MethodThis study utilised genetic and clinical data (n = 1034) collected as part of the International Consortium on Lithium Genetics (ConLi+Gen) project. Polygenic risk scores (PRS) were computed for schizophrenia and major depressive disorder, and then combined with clinical variables using a cross-validated machine-learning regression approach. Unimodal, multimodal and genetically stratified models were trained and validated using ridge, elastic net and random forest regression on 692 patients with bipolar disorder from ten study sites using leave-site-out cross-validation. All models were then tested on an independent test set of 342 patients. The best performing models were then tested in a classification framework.
ResultsThe best performing linear model explained 5.1% (P = 0.0001) of variance in lithium response and was composed of clinical variables, PRS variables and interaction terms between them. The best performing non-linear model used only clinical variables and explained 8.1% (P = 0.0001) of variance in lithium response. A priori genomic stratification improved non-linear model performance to 13.7% (P = 0.0001) and improved the binary classification of lithium response. This model stratified patients based on their meta-polygenic loadings for major depressive disorder and schizophrenia and was then trained using clinical data.
ConclusionsUsing PRS to first stratify patients genetically and then train machine-learning models with clinical predictors led to large improvements in lithium response prediction. When used with other PRS and biological markers in the future this approach may help inform which patients are most likely to respond to lithium treatment.
Characterisation of age and polarity at onset in bipolar disorder
- Janos L. Kalman, Loes M. Olde Loohuis, Annabel Vreeker, Andrew McQuillin, Eli A. Stahl, Douglas Ruderfer, Maria Grigoroiu-Serbanescu, Georgia Panagiotaropoulou, Stephan Ripke, Tim B. Bigdeli, Frederike Stein, Tina Meller, Susanne Meinert, Helena Pelin, Fabian Streit, Sergi Papiol, Mark J. Adams, Rolf Adolfsson, Kristina Adorjan, Ingrid Agartz, Sofie R. Aminoff, Heike Anderson-Schmidt, Ole A. Andreassen, Raffaella Ardau, Jean-Michel Aubry, Ceylan Balaban, Nicholas Bass, Bernhard T. Baune, Frank Bellivier, Antoni Benabarre, Susanne Bengesser, Wade H Berrettini, Marco P. Boks, Evelyn J. Bromet, Katharina Brosch, Monika Budde, William Byerley, Pablo Cervantes, Catina Chillotti, Sven Cichon, Scott R. Clark, Ashley L. Comes, Aiden Corvin, William Coryell, Nick Craddock, David W. Craig, Paul E. Croarkin, Cristiana Cruceanu, Piotr M. Czerski, Nina Dalkner, Udo Dannlowski, Franziska Degenhardt, Maria Del Zompo, J. Raymond DePaulo, Srdjan Djurovic, Howard J. Edenberg, Mariam Al Eissa, Torbjørn Elvsåshagen, Bruno Etain, Ayman H. Fanous, Frederike Fellendorf, Alessia Fiorentino, Andreas J. Forstner, Mark A. Frye, Janice M. Fullerton, Katrin Gade, Julie Garnham, Elliot Gershon, Michael Gill, Fernando S. Goes, Katherine Gordon-Smith, Paul Grof, Jose Guzman-Parra, Tim Hahn, Roland Hasler, Maria Heilbronner, Urs Heilbronner, Stephane Jamain, Esther Jimenez, Ian Jones, Lisa Jones, Lina Jonsson, Rene S. Kahn, John R. Kelsoe, James L. Kennedy, Tilo Kircher, George Kirov, Sarah Kittel-Schneider, Farah Klöhn-Saghatolislam, James A. Knowles, Thorsten M. Kranz, Trine Vik Lagerberg, Mikael Landen, William B. Lawson, Marion Leboyer, Qingqin S. Li, Mario Maj, Dolores Malaspina, Mirko Manchia, Fermin Mayoral, Susan L. McElroy, Melvin G. McInnis, Andrew M. McIntosh, Helena Medeiros, Ingrid Melle, Vihra Milanova, Philip B. Mitchell, Palmiero Monteleone, Alessio Maria Monteleone, Markus M. Nöthen, Tomas Novak, John I. Nurnberger, Niamh O'Brien, Kevin S. O'Connell, Claire O'Donovan, Michael C. O'Donovan, Nils Opel, Abigail Ortiz, Michael J. Owen, Erik Pålsson, Carlos Pato, Michele T. Pato, Joanna Pawlak, Julia-Katharina Pfarr, Claudia Pisanu, James B. Potash, Mark H Rapaport, Daniela Reich-Erkelenz, Andreas Reif, Eva Reininghaus, Jonathan Repple, Hélène Richard-Lepouriel, Marcella Rietschel, Kai Ringwald, Gloria Roberts, Guy Rouleau, Sabrina Schaupp, William A Scheftner, Simon Schmitt, Peter R. Schofield, K. Oliver Schubert, Eva C. Schulte, Barbara Schweizer, Fanny Senner, Giovanni Severino, Sally Sharp, Claire Slaney, Olav B. Smeland, Janet L. Sobell, Alessio Squassina, Pavla Stopkova, John Strauss, Alfonso Tortorella, Gustavo Turecki, Joanna Twarowska-Hauser, Marin Veldic, Eduard Vieta, John B. Vincent, Wei Xu, Clement C. Zai, Peter P. Zandi, Psychiatric Genomics Consortium (PGC) Bipolar Disorder Working Group, International Consortium on Lithium Genetics (ConLiGen), Colombia-US Cross Disorder Collaboration in Psychiatric Genetics, Arianna Di Florio, Jordan W. Smoller, Joanna M. Biernacka, Francis J. McMahon, Martin Alda, Bertram Müller-Myhsok, Nikolaos Koutsouleris, Peter Falkai, Nelson B. Freimer, Till F.M. Andlauer, Thomas G. Schulze, Roel A. Ophoff
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- Journal:
- The British Journal of Psychiatry / Volume 219 / Issue 6 / December 2021
- Published online by Cambridge University Press:
- 25 August 2021, pp. 659-669
- Print publication:
- December 2021
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Background
Studying phenotypic and genetic characteristics of age at onset (AAO) and polarity at onset (PAO) in bipolar disorder can provide new insights into disease pathology and facilitate the development of screening tools.
AimsTo examine the genetic architecture of AAO and PAO and their association with bipolar disorder disease characteristics.
MethodGenome-wide association studies (GWASs) and polygenic score (PGS) analyses of AAO (n = 12 977) and PAO (n = 6773) were conducted in patients with bipolar disorder from 34 cohorts and a replication sample (n = 2237). The association of onset with disease characteristics was investigated in two of these cohorts.
ResultsEarlier AAO was associated with a higher probability of psychotic symptoms, suicidality, lower educational attainment, not living together and fewer episodes. Depressive onset correlated with suicidality and manic onset correlated with delusions and manic episodes. Systematic differences in AAO between cohorts and continents of origin were observed. This was also reflected in single-nucleotide variant-based heritability estimates, with higher heritabilities for stricter onset definitions. Increased PGS for autism spectrum disorder (β = −0.34 years, s.e. = 0.08), major depression (β = −0.34 years, s.e. = 0.08), schizophrenia (β = −0.39 years, s.e. = 0.08), and educational attainment (β = −0.31 years, s.e. = 0.08) were associated with an earlier AAO. The AAO GWAS identified one significant locus, but this finding did not replicate. Neither GWAS nor PGS analyses yielded significant associations with PAO.
ConclusionsAAO and PAO are associated with indicators of bipolar disorder severity. Individuals with an earlier onset show an increased polygenic liability for a broad spectrum of psychiatric traits. Systematic differences in AAO across cohorts, continents and phenotype definitions introduce significant heterogeneity, affecting analyses.
PP531 Quality Of Life Of Patients With Long-Chain Fatty Acid Oxidation Disorders Before And During Treatment With Triheptanoin
- Eliza Kruger, Deborah Marsden, Arielle Bensimon, Erin Cook, Eli Orvis, Hongbo Yang, Jill Mayhew, Nina Thomas
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- Journal:
- International Journal of Technology Assessment in Health Care / Volume 36 / Issue S1 / December 2020
- Published online by Cambridge University Press:
- 28 December 2020, p. 41
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Introduction
Long-chain fatty acid oxidation disorders (LC-FAOD) are a group of serious diseases in which patients are at risk of metabolic decompensation, resulting in cardiomyopathy, hypoglycemia and rhabdomyolysis and premature mortality. In addition, LC-FAOD are a burdensome disease that adversely effects quality of life (QoL) via symptoms of muscle pain, fatigue, and a difficult diet. Previous studies have reported improvements in QoL during treatment with triheptanoin as measured by short form (SF) instruments. This study sought to convert the QoL measure into a utility value for a sample of patients with LC-FAOD at baseline and 78 weeks during treatment with triheptanoin.
MethodsIn an open-label Phase 2 study of triheptanoin (UX007-CL201, NCT01886378), caregivers of patients (n = 9/23 enrolled) or patients aged 18+ years (n = 6/6 enrolled) completed the SF-10 or the SF-12v2, respectively. Component summary scores at baseline and 78-week during treatment period were converted to EuroQol-Five Dimension (EQ-5D) utility (with zero representing death and 1.0 perfect health) using a published conversion algorithm (Lawrence and Fleishman 2004). Generalized linear mixed-effects models with individual-level random effects were used to estimate the utility values.
ResultsAt baseline, patients’ utility was estimated to be 0.365 (standard error [SE] = 0.090) compared with 0.629 (SE = 0.072) 78-weeks during treatment, a significant improvement (p = 0.0073). In a sensitivity analysis using SF-12v2 data only (that is, only adult patients), utility estimates were 0.498 (SE = 0.084) at baseline versus 0.690 (SE = 0.068) during treatment (p = 0.0499). No patients had a major clinical event during the SF instrument recall period, indicating the benefit was driven by day-to-day improvement in QoL.
ConclusionsTreatment with triheptanoin resulted in a substantial improvement in daily QoL for patients with LC-FAOD. Limitations of this study include that the estimation of utilities is from a single-arm study with small sample sizes and that the assessment of utility was based on a conversion algorithm rather than direct measurement. Nevertheless, results indicate significant improvement in QoL for patients treated with triheptanoin.
Deciduous trees as lichen phorophytes: biodiversity and colonization patterns under common garden conditions
- Hanne Marie Ellegård Larsen, Eric Steen Hansen, Thomas Nord-Larsen, Hanne Nina Rasmussen
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- Journal:
- The Lichenologist / Volume 52 / Issue 3 / May 2020
- Published online by Cambridge University Press:
- 03 June 2020, pp. 221-232
- Print publication:
- May 2020
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Common gardens are experimental plantations for comparing the performance of tree species while eliminating many of the variables that prevail in natural tree stands. The aim of this study was to evaluate the biodiversity of corticolous lichens on Danish tree species (Acer pseudoplatanus, Alnus glutinosa, Betula pendula, Fagus sylvatica, Fraxinus excelsior, Quercus robur and Tilia cordata) under common garden conditions and to examine the height distribution of particular lichen species. Observations were recorded through regular sampling of at least 36 lichen species on the main stems (from the base of the stem to the treetops) of 44-year-old trees at four common garden sites. Acer pseudoplatanus and Fraxinus excelsior had the greatest lichen species richness and Shannon diversity values while these measures were significantly lower for Betula pendula and Fagus sylvatica. The distribution of lichen species appeared biased among tree species. The general lichen distribution and relative sample height were weakly related (nonmetric multidimensional scaling). However, single lichen species showed a clear differential distribution along the tree stem (P < 0.001, non-parametric multiplicative regression and logistic log-binomial regression). Lepraria incana, Pseudosagedia aenea and Arthonia atra were mainly found at the stem base while Lecanora carpinea, L. chlarotera, Lecidella elaeochroma, Physcia tenella and Xanthoria parietina, were most abundant at around 70% of the total tree height. The differential distribution of single lichen species presumably reflects different specific requirements during spore germination and thallus growth. By isolating the unique effect of key variables (tree species and height), this study contributes to the knowledge base of corticolous lichen ecology.
Moth-inspired methods for particle capture on a cylinder
- Thomas L. Spencer, Nina Mohebbi, Guangyuan Jin, Matthew L. Forister, Alexander Alexeev, David L. Hu
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- Journal:
- Journal of Fluid Mechanics / Volume 884 / 10 February 2020
- Published online by Cambridge University Press:
- 17 December 2019, A34
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We study particle capture on an angled cylinder at a range of Péclet numbers. This system was inspired by the plumose antennae of certain species of male moths that intercept female pheromones at low Péclet numbers of 0.9–23. We use confocal microscopy to measure the branching patterns of 49 moths, spanning 12 families and two orders of magnitude in mass. Among the three levels of hierarchy in antennae, we find the middle level has a prevalent branching angle, $52^{\circ }\pm 12^{\circ }$ across our study set. Such intermediate branching angles are a surprising way to intercept molecules because they do not maximize the exposed surface area. To understand the benefits of angling cylinders into the flow, we study particle collection at high Péclet number using $10~\unicode[STIX]{x03BC}\text{m}$ drops that are several orders of magnitude larger than moth pheromones. Wind tunnel tests show that cylinders angled at $30^{\circ }{-}60^{\circ }$ are optimal for collection of particles, collecting 30 % more than when perpendicular to the flow. Simulations and smoke visualization show that angled cylinders bend incoming streamlines, creating a lingering effect near the cylinder that can enhance deposition by diffusion. We surmise that the optimal angle arises from a trade-off between the lingering effect, which decreases with increasing angle of the cylinder, and the cylinder’s increasing projected area as it is turned more perpendicular to the flow. Using a mathematical model, we show that only cylinders at low Péclet number show improved collection at intermediate angles. Thus, we cannot rationalize the high collection rates in our wind tunnel experiments at high Péclet number. We hope that our study will inspire more research into bio-inspired particle collection of angled surfaces, and find applications in sensors and filters.
Use of Predictive Modeling to Plan for Special Event Medical Care During Mass Gathering Events
- Rachel L. Allgaier, Nina Shaafi-Kabiri, Carla A. Romney, Lee A. Wallis, John Joseph Burke, Jaspreet Bhangu, Kevin C. Thomas
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- Journal:
- Disaster Medicine and Public Health Preparedness / Volume 13 / Issue 5-6 / December 2019
- Published online by Cambridge University Press:
- 06 June 2019, pp. 874-879
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Objectives:
In 2010, South Africa (SA) hosted the Fédération Internationale de Football Association (FIFA) World Cup (soccer). Emergency Medical Services (EMS) used the SA mass gathering medicine (MGM) resource model to predict resource allocation. This study analyzed data from the World Cup and compared them with the resource allocation predicted by the SA mass gathering model.
Methods:Prospectively, data were collected from patient contacts at 9 venues across the Western Cape province of South Africa. Required resources were based on the number of patients seeking basic life support (BLS), intermediate life support (ILS), and advanced life support (ALS). Overall patient presentation rates (PPRs) and transport to hospital rates (TTHRs) were also calculated.
Results:BLS services were required for 78.4% (n = 1279) of patients and were consistently overestimated using the SA mass gathering model. ILS services were required for 14.0% (n = 228), and ALS services were required for 3.1% (n = 51) of patients. Both ILS and ALS services, and TTHR were underestimated at smaller venues.
Conclusions:The MGM predictive model overestimated BLS requirements and inconsistently predicted ILS and ALS requirements. MGM resource models, which are heavily based on predicted attendance levels, have inherent limitations, which may be improved by using research-based outcomes.
Expansion of the Priority Review Voucher Program Under the 21st Century Cures Act: Implications for Innovation and Public Health
- Michael S. Sinha, Nina Jain, Thomas Hwang, Aaron S. Kesselheim
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- Journal:
- American Journal of Law & Medicine / Volume 44 / Issue 2-3 / May 2018
- Published online by Cambridge University Press:
- 06 January 2021, pp. 329-341
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- May 2018
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The U.S. federal government awards a priority review voucher (“PRV”) to a pharmaceutical manufacturer after the Food and Drug Administration (“FDA”) approves a product for one of a list of voucher-eligible indications. The voucher, which can be transferred or sold, allows the company to accelerate the review timeline of another product for any indication. The PRV program was proposed in 2006 as an incentive for research and development for neglected diseases, such as dengue and leishmaniasis.
Neglected tropical diseases (“NTDs”) predominantly affect the world’s poorest populations and are associated with significant morbidity and mortality. Despite their global public health importance, neglected diseases were estimated to account for less than 1% of pharmaceutical research and development expenditures. The voucher program was intended to address this gap between investment and disease burden: “[t]he major obstacle to stimulating the R&D of new medicines for neglected diseases is lowincome nations' inability to pay for such medicines.” The voucher would provide an additional financial incentive to fund clinical development of these products without requiring additional appropriations from Congress.
A clinimetric analysis of a BPRS-6 scale for schizophrenia severity
- Per Bech, Stephen F Austin, Nina Timmerby, Thomas A Ban, Stine Bjerrum Møller
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- Journal:
- Acta Neuropsychiatrica / Volume 30 / Issue 4 / August 2018
- Published online by Cambridge University Press:
- 07 February 2018, pp. 187-191
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Objective
A restricted Brief Psychiatric Rating Scale (BPRS-6) with the six schizophrenia specific items from the Positive and Negative Syndrome Scale (PANSS) has been investigated. These six items from the PANSS have recently been found to have both clinical validity and ‘unidimensionality’ in measuring the severity of schizophrenic states. The primary objective of this study was to evaluate the clinical validity of the BPRS-6. The secondary objective was to evaluate the ‘unidimensionality’ of the BPRS-6 by an ‘item response theory’ model.
MethodsThe BPRS-6 was scored independently by two psychiatrists and two psychologists while viewing six open-ended videotaped interviews in patients with a DSM-III diagnosis of schizophrenia. The interviews were conducted by Heinz E. Lehmann, an experienced psychiatrist. They were focused on the psychopathology that contributed most to the ‘severity’ of the patient’s clinical state.
ResultsThe BPRS-6 with three positive symptoms (delusions, conceptual disorganisation, hallucinations) and three negative symptoms (blunted affect, emotional withdrawal, poverty of speech) was found to be clinically valid and captured the variables that contribute most to the severity of schizophrenia. The BPRS-6 was also found to have acceptable ‘unidimensionality’ (coefficient of homogeneity 0.45) and inter-rater reliability (inter-class-coefficient 0.81).
ConclusionThe BPRS-6 was found to capture the information that translates into the severity of schizophrenia. It has also acceptable psychometric validity.
Grounding-line migration in plan-view marine ice-sheet models: results of the ice2sea MISMIP3d intercomparison
- Frank Pattyn, Laura Perichon, Gaël Durand, Lionel Favier, Olivier Gagliardini, Richard C.A. Hindmarsh, Thomas Zwinger, Torsten Albrecht, Stephen Cornford, David Docquier, Johannes J. Fürst, Daniel Goldberg, G. Hilmar Gudmundsson, Angelika Humbert, Moritz Hütten, Philippe Huybrechts, Guillaume Jouvet, Thomas Kleiner, Eric Larour, Daniel Martin, Mathieu Morlighem, Anthony J. Payne, David Pollard, Martin Rückamp, Oleg Rybak, Hélène Seroussi, Malte Thoma, Nina Wilkens
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- Journal:
- Journal of Glaciology / Volume 59 / Issue 215 / 2013
- Published online by Cambridge University Press:
- 10 July 2017, pp. 410-422
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Predictions of marine ice-sheet behaviour require models able to simulate grounding-line migration. We present results of an intercomparison experiment for plan-view marine ice-sheet models. Verification is effected by comparison with approximate analytical solutions for flux across the grounding line using simplified geometrical configurations (no lateral variations, no buttressing effects from lateral drag). Perturbation experiments specifying spatial variation in basal sliding parameters permitted the evolution of curved grounding lines, generating buttressing effects. The experiments showed regions of compression and extensional flow across the grounding line, thereby invalidating the boundary layer theory. Steady-state grounding-line positions were found to be dependent on the level of physical model approximation. Resolving grounding lines requires inclusion of membrane stresses, a sufficiently small grid size (<500 m), or subgrid interpolation of the grounding line. The latter still requires nominal grid sizes of <5 km. For larger grid spacings, appropriate parameterizations for ice flux may be imposed at the grounding line, but the short-time transient behaviour is then incorrect and different from models that do not incorporate grounding-line parameterizations. The numerical error associated with predicting grounding-line motion can be reduced significantly below the errors associated with parameter ignorance and uncertainties in future scenarios.
The Aphasia Action, Success, and Knowledge Programme: Results from an Australian Phase I Trial of a Speech-Pathology-Led Intervention for People with Aphasia Early Post Stroke
- Brooke Ryan, Kyla Hudson, Linda Worrall, Nina Simmons-Mackie, Emma Thomas, Emma Finch, Kathy Clark, Jennifer Lethlean
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- Journal:
- Brain Impairment / Volume 18 / Issue 3 / December 2017
- Published online by Cambridge University Press:
- 30 March 2017, pp. 284-298
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Background: Speech pathologists work to optimise communication and reduce the emotional and social impact of communication disability in patients with aphasia but need evidence-based interventions to effectively do so.
Objective: This phase 1 study aims to evaluate an Australian speech-pathology-led intervention called the Aphasia Action, Success, and Knowledge (Aphasia ASK) programme for patients with aphasia early post stroke.
Methods: A convergent parallel mixed-methods design was utilised. The intervention included up to six individual face-to-face sessions with seven participants with aphasia and their nominated family member(s). Quantitative outcomes assessing mood, quality of life, and communication confidence were conducted for the participants with aphasia. Follow-up interviews were conducted with both participants with aphasia and family members to determine their perceptions of the programme.
Results: Significant improvements were found in communication confidence and mood after treatment and the gains were maintained at 3-month follow-up. Participants with aphasia and their family members reported a good level of satisfaction with the programme.
Conclusions: Findings suggest the Aphasia ASK programme is a suitable intervention with positive initial outcomes for people with aphasia. A larger scale evaluation with a greater variety of participants is now required. An Australian cluster randomised control trial is planned.
Molecular mechanisms of xeroderma pigmentosum (XP) proteins
- Sandra C. Koch, Nina Simon, Charlotte Ebert, Thomas Carell
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- Journal:
- Quarterly Reviews of Biophysics / Volume 49 / 2016
- Published online by Cambridge University Press:
- 10 February 2016, e5
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Nucleotide excision repair (NER) is a highly versatile and efficient DNA repair process, which is responsible for the removal of a large number of structurally diverse DNA lesions. Its extreme broad substrate specificity ranges from DNA damages formed upon exposure to ultraviolet radiation to numerous bulky DNA adducts induced by mutagenic environmental chemicals and cytotoxic drugs used in chemotherapy. Defective NER leads to serious diseases, such as xeroderma pigmentosum (XP). Eight XP complementation groups are known of which seven (XPA–XPG) are caused by mutations in genes involved in the NER process. The eighth gene, XPV, codes for the DNA polymerase ɳ, which replicates through DNA lesions in a process called translesion synthesis (TLS). Over the past decade, detailed structural information of these DNA repair proteins involved in eukaryotic NER and TLS have emerged. These structures allow us now to understand the molecular mechanism of the NER and TLS processes in quite some detail and we have begun to understand the broad substrate specificity of NER. In this review, we aim to highlight recent advances in the process of damage recognition and repair as well as damage tolerance by the XP proteins.