We use cookies to distinguish you from other users and to provide you with a better experience on our websites. Close this message to accept cookies or find out how to manage your cookie settings.
To save content items to your account,
please confirm that you agree to abide by our usage policies.
If this is the first time you use this feature, you will be asked to authorise Cambridge Core to connect with your account.
Find out more about saving content to .
To save content items to your Kindle, first ensure no-reply@cambridge.org
is added to your Approved Personal Document E-mail List under your Personal Document Settings
on the Manage Your Content and Devices page of your Amazon account. Then enter the ‘name’ part
of your Kindle email address below.
Find out more about saving to your Kindle.
Note you can select to save to either the @free.kindle.com or @kindle.com variations.
‘@free.kindle.com’ emails are free but can only be saved to your device when it is connected to wi-fi.
‘@kindle.com’ emails can be delivered even when you are not connected to wi-fi, but note that service fees apply.
Recent guidance from UK health authorities strongly cautions against the use of valproic acid (VPA) in persons under 55 because of reevaluated risk of teratogenicity.
Objective
To summarize the extant literature documenting VPA-associated anatomical, behavioral, and cognitive teratogenicity.
Method
Pubmed, Medline, Cochrane Library, PsychInfo, Embase, Scopus, Web of Science, and Google Scholar were searched in accordance with PRISMA guidelines. Collected data covered study design, participant characteristics, anatomical, behavioral, or cognitive effects, and folic acid outcomes.
Results
122 studies were identified meeting inclusion comprised of studies evaluating anatomical (n = 67), behavioral (n = 28), and cognitive (n = 47) teratogenicity. Twenty studies were identified reporting on the risk mitigation effects of folic acid supplementation. Prenatal VPA exposure is associated with anatomical teratogenicity including major congenital malformations (odds ratio [OR] 2.47–9.30; p < 0.005). Behavioral teratogenicity including autism (OR 1.70–4.38), impaired motor development (OR 7.0), and ADHD (OR 1.39) are also significantly associated with VPA exposure. VPA was associated with intellectual disability and low IQ (hazard ratio [HR] 2.4–4.48, verbal intelligence: Spearman’s ρ = −0.436, respectively). Teratogenic effects were dose-dependent across all domains and were significant when compared with controls and other antiepileptic drugs (eg, carbamazepine, lamotrigine, and levetiracetam). Folic acid supplementation does not significantly reduce the hazard associated with VPA.
Conclusions
VPA is significantly associated with anatomical, behavioral, and cognitive teratogenicity. Folic acid supplementation does not abrogate the risk of teratogenicity associated with VPA exposure. Available evidence supports recommendations to reduce VPA exposure in women of reproductive age.
According to International Union for the Conservation of Nature (IUCN) guidelines, all species must be assessed against all criteria during the Red Listing process. For organismal groups that are diverse and understudied, assessors face considerable challenges in assembling evidence due to difficulty in applying definitions of key terms used in the guidelines. Challenges also arise because of uncertainty in population sizes (Criteria A, C, D) and distributions (Criteria A2/3/4c, B). Lichens, which are often small, difficult to identify, or overlooked during biodiversity inventories, are one such group for which specific difficulties arise in applying Red List criteria. Here, we offer approaches and examples that address challenges in completing Red List assessments for lichens in a rapidly changing arena of data availability and analysis strategies. While assessors still contend with far from perfect information about individual species, we propose practical solutions for completing robust assessments given the currently available knowledge of individual lichen life-histories.
Almost half of countries globally are implementing national strategies to lower population salt intake towards the World Health Organization’s target of a 30% reduction by 2025(1). However, most are yet to lower population salt intake(1). We conducted process evaluations of national salt reduction strategies in Malaysia and Mongolia to understand the extent to which they were implemented and achieving their intended outcomes, using the findings to generate insights on how to strengthen strategies and accelerate population salt reduction. Mixed methods process evaluations were conducted at the mid-point of implementation of the strategies in Malaysia (2018-19) and Mongolia (2020-21)(2). Guided by theoretical frameworks, information on the implementation, mechanism and contextual barriers and enablers of the strategies were collected through desk-based reviews of documents related to salt reduction, interviews with key stakeholders (n = 12 Malaysia, n = 10 Mongolia), and focus group discussions with health professionals in Malaysia (n = 43) and health provider surveys in Mongolia (n = 12). Both countries generated high-quality evidence about salt intake and salt levels in foods, and culturally-specific education resources in 3 and 5 years respectively. However, in Malaysia there was moderate dose delivered and low reach in terms of education and reformulation activities. Within 5 years, Mongolia implemented education among schools, health professionals and food producers on salt reduction with high reach but with moderate dose and reach among the general population. There were challenges in both countries with respect to implementing legislative interventions and both could improve the scaling up of their reformulation and education activities to have population-wide reach and impact. In the first half of Malaysia’s and Mongolia’s strategies, both countries generated necessary evidence and education materials, mobilised health professionals to deliver salt reduction education and achieved small-scale salt reformulation in foods. However, both faced challenges in implementing regulatory policies and the scaling up of their reformulation and education activities to have population-wide reach and impact could be strengthened. Similar process evaluations of existing salt reduction strategies are needed to strengthen intervention delivery and inform areas for adaptation, to aid achievement of the WHO’s global target of a 30% reduction in population salt intake by 2025.
While the diversity of foliicolous lichen-forming fungi has been explored in substantial depth, relatively little attention has been paid to their algal symbionts. We studied the unicellular green phycobionts of the lecanoralean lichens Bacidina (Ramalinaceae), Byssoloma, Fellhanera and Tapellaria (Pilocarpaceae) and graphidalean Gyalectidium (Gomphillaceae) from two extratropical foliicolous communities in continental Spain and the Canary Islands. We examined the pyrenoids of algal symbionts within thalli using TEM, and obtained several algal nrSSU and rbcL sequences from whole thalli, and also from cultures isolated from some of these lichens. Pyrenoid structure and molecular sequence data provided support for recognizing Chloroidium (Watanabeales, Trebouxiophyceae) as phycobiont in thalli of Byssoloma subdiscordans and Fellhanera bouteillei (Pilocarpaceae) in both communities. Bacidina apiahica (Ramalinaceae) and Tapellaria epiphylla (Pilocarpaceae) likewise appeared to partner with Chloroidium based on the presence of the same pyrenoid type, although we were able to obtain a phycobiont sequence only from a culture isolate of the latter. These results contrast with those obtained previously from a foliicolous lichen community in southern Florida, which revealed only strains of Heveochlorella (Jaagichlorella) as phycobiont of foliicolous Pilocarpaceae and Gomphillaceae. On the other hand, the pyrenoid we observed in the phycobionts associated with Gyalectidium setiferum and G. minus corresponded to that of Heveochlorella (Jaagichlorella). However, the poor quality of the phycobiont sequence data obtained from G. minus, probably due to the presence of epibiontic algae, could not provide additional perspective on the pyrenoid structure observations. Nonetheless, clear differences in pyrenoid ultrastructure can allow Chloroidium and Heveochlorella phycobionts to be distinguished from each other in TEM. Our results indicate a greater diversity of unicellular green-algal symbionts in foliicolous communities from Spain than previously observed in other geographical areas, and suggest that further studies focused on symbiont pairing in these communities might reveal distinctive and varied patterns of phycobiont preference.
Shortness of breath, or dyspnea, is the subjective experience of breathing discomfort and is a common, distressing, and debilitating symptom of lung cancer. There are no efficacious pharmacological treatments, but there is suggestive evidence that cognitive–behavioral treatments could relieve dyspnea. For this, understanding the psychological, behavioral, and social factors that may affect dyspnea severity is critical. To this end, patients with dyspnea were interviewed with questions framed by the cognitive–behavioral model—emphasizing thoughts, emotions, and behaviors as contributors and outcomes of dyspnea.
Methods
Two trained individuals conducted semi-structured interviews with lung cancer patients (N = 15) reporting current dyspnea. Interviews assessed patients’ cognitive–behavioral experiences with dyspnea. Study personnel used a grounded theory approach for qualitative analysis to code the interviews. Inter-rater reliability of codes was high (κ = 0.90).
Results
Thoughts: Most common were patients’ catastrophic thoughts about their health and receiving enough oxygen when breathless. Emotions: Anxiety about dyspnea was the most common, followed by anger, sadness, and shame related to dyspnea. Behaviors: Patients rested and took deep breaths to relieve acute episodes of dyspnea. To reduce the likelihood of dyspnea, patients planned their daily activity or reduced their physical activity at the expense of engagement in hobbies and functional activities.
Significance of results
Patients identified cognitive–behavioral factors (thoughts, emotions, and behaviors) that coalesce with dyspnea. The data provide meaningful insights into potential cognitive–behavioral interventions that could target contributors to dyspnea.
A machine learning model was created to predict the electron spectrum generated by a GeV-class laser wakefield accelerator. The model was constructed from variational convolutional neural networks, which mapped the results of secondary laser and plasma diagnostics to the generated electron spectrum. An ensemble of trained networks was used to predict the electron spectrum and to provide an estimation of the uncertainty of that prediction. It is anticipated that this approach will be useful for inferring the electron spectrum prior to undergoing any process that can alter or destroy the beam. In addition, the model provides insight into the scaling of electron beam properties due to stochastic fluctuations in the laser energy and plasma electron density.
Mentally ill patients have rates of medical comorbidity and mortality higher than the rest of the population. They require adequate medical care that isn't usually.
Objectives:
Emphasis on physical health problems affecting the mentally ill patients, analyze situations that may motivate and possible solutions.
Methods:
Bibliographical review in the literature and pub med using key words: “medical comorbidity, severe mental illness, psychopharmacological treatments”
Results:
Mentally ill patients have greater medical comorbidity and higher mortality rate than the general population. in patients with schizophrenia life expectancy is 20% lower and mortality risk of 1.5–3 times higher than the rest of population. Affective disorders are associated with a standardized mortality ratio for medical reasons also high. Studies show that excess mortality in patients with severe mental illness is 60% due to natural causes and 40% to unnatural causes (28% suicide and 12% accidents). This increased mortality is mainly due to cardio-respiratory and infectious disease. Low socioeconomic class, lack of social care, poor medical care, bad habits (poor diet, sedentary, toxics) and adverse effects of psychopharmacological treatments are the main factors. Despite this, detection and treatment of physical illness is low. It is estimated that between 30% and 47% of these patients are untreated.
Conclusions:
Improved medical care of these patients would improve their performance and quality of life. A system for each type of mental health to screening, assessment, diagnosis and treatment of somatic diseases, and a protocol for referral to appropiate medical/surgical centers are required.
Psychotherapy Focused on Psychic Representation (PFPR) is a new time limited dynamic psychotherapy for the treatment of Borderline Personality Disorder. It is a manualized psychodynamic technique based on brief psychoanalytic psychotherapies principles and designed to be applied in the framework of public care services. A randomized and controlled study with a sample of 53 patients was conducted to assess PFPR's efficacy. We are reporting the final results at the end of treatment and at the 6 and 12 months of follow up.
Methods:
Both groups, the experimental (n=25) and control group (n=28) received treatment as usual. The experimental group received 20 additional PFPR sessions performed by four therapists with homogenous characteristics, specifically trained in this technique. The main outcome variables measures were: Severity global index of SCL-90-R, Barrat Impulsivity Scale scores and Social Adaptation (SASS score). Baseline and conditions at the end of treatment and at the 6 and 12 months of follow up period were compared.
Results and Conclusions:
Results showed significantly better outcomes for the experimental group in all main variables and in most of the secondary ones at the end of treatment. At 6 months follow up, the significant differences remain in level of impulsivity and some other secondary variables. At 12 months follow up the experimental group shows better results in all variables but only depressive symptoms measurement remains significant.
A recent field study indicated that thalli of the beard lichen Ramalina usnea undergo diffuse (“intercalary”) growth throughout their length. We examined thallus sections with TEM to better understand how the highly thickened cell walls of the prosoplectenchymatous cortex behave under conditions of continued expansion. Cell protoplasts were surrounded by massive accumulations of structured electron-dense wall layers interspersed with amorphous, electron-transparent substances, visible as concentric rings in transverse section. Nearest the protoplast, electron-dense wall layers were distinct and more or less alternated with irregular deposits of electron-transparent material. With increasing distance from the protoplast, the electron-dense wall layers were increasingly disrupted and intermixed among the electron-transparent materials. New cell branches grew through the accumulated wall materials, interrupting the layers they penetrated while producing their own concentric wall layers. The differing amounts of cell wall material accumulated was further indication of the different relative ages of such neighbouring cells. These observations suggest that cell walls are disrupted by diffuse tissue expansion and continually replaced by new walls and wall materials deposited to their interior at the interface with the protoplast. This pattern of development, documented previously in R. menziesii and U. longissima, suggests that component cells of lichen prosoplectenchyma behave quite differently from those of diffusely expanding filaments studied in non-lichen-forming fungi, where a single, discrete cell wall is maintained throughout growth.
OBJECTIVES/SPECIFIC AIMS: The aim of this study is to determine whether quantitative measures of knee structures including effusion, bone marrow lesions, cartilage, and meniscal damage can improve upon an existing model of demographic and clinical characteristics to classify accelerated knee osteoarthritis (AKOA). METHODS/STUDY POPULATION: We conducted a case-control study using data from baseline and four annual follow-up visits from the osteoarthritis initiative. Participants had no radiographic knee osteoarthritis (KOA) at baseline. AKOA is defined as progressing from no KOA to advance-stage KOA in at least 1 knee within 48 months. AKOA knees were matched 1:1 based on sex to (1) participants who did not develop KOA within 48 months and (2) participants who developed KOA but not AKOA. Analyses were person based. Classification and regression tree analysis was used to determine the important variables and percent of variance explained. RESULTS/ANTICIPATED RESULTS: A previous classification and regression tree analysis found that age, BMI, serum glucose, and femorotibial angle explained 31% of the variability between those who did and did not develop AKOA. Including structural measurements as candidate variables yielded a model that included effusion, BMI, serum glucose, cruciate ligament degeneration and coronal slope and explained 39% of the variability. DISCUSSION/SIGNIFICANCE OF IMPACT: Knee structural measurements improve classification of participants who developed AKOA Versus those who did not. Further research is needed to better classify patients at risk for AKOA.
Although relapse in psychosis is common, a small proportion of patients will not relapse in the long term. We examined the proportion and predictors of patients who never relapsed in the 10 years following complete resolution of positive symptoms from their first psychotic episode.
Method
Patients who previously enrolled in a 12-month randomized controlled trial on medication discontinuation and relapse following first-episode psychosis (FEP) were followed up after 10 years. Relapse of positive symptoms was operationalized as a change from a Clinical Global Impression scale positive score of <3 for at least 3 consecutive months to a score of ⩾3 (mild or more severe). Baseline predictors included basic demographics, premorbid functioning, symptoms, functioning, and neurocognitive functioning.
Results
Out of 178 first-episode patients, 37 (21%) never relapsed during the 10-year period. Univariate predictors (p ⩽ 0.1) of patients who never relapsed included a duration of untreated psychosis (DUP) ⩽30 days, diagnosed with non-schizophrenia spectrum disorders, having less severe negative symptoms, and performing better in logical memory immediate recall and verbal fluency tests. A multivariate logistic regression analysis further suggested that the absence of any relapsing episodes was significantly related to better short-term verbal memory, shorter DUP, and non-schizophrenia spectrum disorders.
Conclusions
Treatment delay and neurocognitive function are potentially modifiable predictors of good long-term prognosis in FEP. These predictors are informative as they can be incorporated into an optimum risk prediction model in the future, which would help with clinical decision making regarding maintenance treatment in FEP.
How growth is distributed within the morphologically diverse thalli of lichens is still poorly known and the anatomical mechanisms involved are not well understood. This work applies electron microscopy (SEM and TEM) to examine cell- and tissue-level events in the umbilicate thallus of Lasallia pustulata, whose pattern of expansion was the subject of a previous field study. Stacks of epinecral tissue accumulating at the thallus surface showed broadening bases and recurring rupture attributable to diffuse expansion of the living tissue below. Cortical cells, dividing anticlinally, adjoined septa to previous septa, indicating parenchymatous divisions. These observations are all consistent with previous contentions that mature, organized tissues within the thallus are capable of continued diffuse growth. They provide a developmental explanation for the morphology of the epinecral layer and suggest that anatomical characteristics may be helpful in recognizing diffuse growth patterns. Parenchymatous cell divisions, believed until recently to never occur in lichen thallus tissues, are shown to play a developmental role in the diffuse growth of the umbilicate lichen thallus.
This paper provides evidence of appreciable amounts of Zn (up to 0.52 a.p.f.u.) residing in the crystal structure of trioctahedral vermiculite; the results were obtained by a combination of experimental methods (X-ray diffraction, energy dispersive X-ray spectrometry, electron microprobe analysis and selective chemical extractions) and theoretical studies based on density functional theory (DFT). Vermiculite occurs in size fractions ranging from 10 to 40 μm of near-neutral soils naturally enriched in Zn (up to 8110 mg kg–1) due to the weathering of carbonate-hosted Zn-Pb deposits in SW Spain. Zinc was partitioned among the various pedogenic phases during soil formation, but the larger part (>80%) was concentrated in the residual silicate fraction. The soil exchangeable Zn pool was found to be virtually negligible. The DFT calculations support the hypothesis that the role of vermiculite is an effective sink for geogenic Zn; this is consistent, in terms of energetic stability, with the assumption that most Zn is structurally bound in octahedral sheets rather than in the interlayer exchange sites. The findings conclusively indicate that the potential mobility of Zn should remain low under the present soil conditions.
Three natural amphibole samples collected from the former vermiculite mine near Libby, Montana. USA, have been analysed by Rietveld X-ray powder diffraction (XRPD) refinement and Fourier transform infrared spectroscopy (FTIR) in the OH-stretching region. The same materials have been analysed previously by electron microprobe analysis (EMPA), Mössbauer spectroscopy and structure refinement (SREF) single crystal X-ray diffraction (SC-XRD), which revealed that these amphiboles have a crystal chemical formula very close to an intermediate composition between winchite and richterite, i.e. AA0.5BNaCaCMg4.5M3+T0.5Si8O22(OH)2 (A = Na and/or K; M3+ = Fe3+ and/or Al). The Rietveld analysis showed the powder samples used for the experiments here to be composed only of amphibole. This in turn allowed us to use FTIR OH-stretching data to derive cation ordering on these powder samples. The three FTIR spectra are quite similar and up to four components can be fitted to the patterns. The two lower-frequency components (labelled A and B) can be attributed to a local O(3)-H dipole surrounded by M(1)M(3)Mg3 and M(1)M(3)Mg2Fe2+; (respectively), an empty A site and rSi8 environments; on the contrary, the higher-frequency C and D bands indicate the presence of an occupied A site. The FTIR OH-stretching data alone allow us to calculate the site occupancy of the A, M(1)–M(3) and T sites with confidence, as compared with previously published data. By contrast M(4)- and M(2)-site occupancies are more difficult to evaluate. This study takes advantage of the large database of well characterized synthetic amphiboles, built over the last two decades. The comparison of vibrational spectroscopy data with micro-chemical and crystallographic data reported in this study demonstrate that the FTIR OH-stretching method alone is a valuable and rapid method to derive or at least sensibly constrain site occupancy for natural amphiboles. A much more detailed cation site occupancy can be obtained by combining micro-chemical and FTIR OH-stretching data.
Background: In the elderly population, use of antithrombotic therapy (AT), antiplatelets (AP – aspirin, clopidogrel) and/or anticoagulants (AC – warfarin, DoAC – Dabigatran, Rivaroxaban, Apixaban), to prevent thrombo-embolic events must be carefully weighed against the risk of intracranial hemorrhage (ICH) with trauma. We hypothesize that for all patients 65yro+ with head trauma, those on AT will be more likely to sustain a traumatic brain injury, ICH, and poorer outcomes. Methods: Data was collected from all head trauma patients 65yo+ presenting to our tertiary trauma center (level 1) over a 24-month period; age, gender, injury mechanism, medications, International Normalized Ratio, reversal therapy, Glasgow Coma Scale (GCS), ICH, surgery, Extended Glasgow Outcome Scale score (GOSE) and mortality. Results: 1365 patients were identified; 724 on AT (413 AP, 151 AC, 59 DoAC, 48 2AP, 38 AP+AC, 15 AP+DoAC) and 474 not (non-AT). When adjusted for covariates, AT patients were more likely to have ICH (p=0.0004), more invasive surgical interventions (p=0.0188), functional dependency (GOSE≤4; p<0.0001) and mortality (p<0.0001). Risk of mortality is notably high with 2AP (OR 5.74; p=0.0003) and AC+AP (OR 4.12; p=0.0118). Conclusions: Elderly trauma patients on AT, especially combination therapy, have higher risks of ICH and poorer outcomes compared to those who are not.
Objectives: Glioblastoma is a lethal disease in the elderly population. We aimed to evaluate disease and treatment outcomes in the oldest-old patients. Methods: Patients >80 years old with histologically confirmed glioblastoma treated between 2004 and 2009 were identified. We included patients managed with best supportive care (BSC), temozolomide (TMZ) alone, radiotherapy (RT) alone, or concomitantly with TMZ (CRT). Survival outcomes were analyzed using the Kaplan–Meier method. Results: Ultimately, 48 patients were analyzed. Median age and Eastern Cooperative Oncology Group (ECOG) Performance Status were 82 years and 2, respectively. The median Age-Adjusted Charlson Index (AAC) was 6. Gross total and subtotal resections were performed in 16.7% and 18.8% of patients, respectively. Biopsy followed by RT alone was the treatment modality for 23/48 (47.9%), while 17/48 (35.4%) received surgery followed by RT alone or CRT. A total of 8 (16.7%) were managed with BSC after biopsy. Median overall survival (OS) and progression-free survival (PFS) were 4.1 (95% confidence interval [95% CI] 3.3-4.9) and 2.7 (95% CI 1.5-3.9) months, respectively. Improved median OS was observed in those treated with surgical resection followed by RT alone or CRT (7.1 months), compared to biopsy followed by RT alone (4.2 months) or BSC (2.0 months; p=0.002). Surgical resection, age≤85, and AAC<6 were associated with better OS (p=0.032, p=0.031, and p=0.02, respectively). Cause of death was neurological progression in 56% of cases. RT was well-tolerated. Conclusions: PFS and OS outcomes remain poor in the oldest-old patients (>80 years old). Younger age, lower AAC, surgical resection, and adjuvant treatment were associated with improved OS.
DW-NOMINATE scores for the U.S. Congress are widely used measures of legislators' ideological locations over time. These scores have been used in a large number of studies in political science and closely related fields. In this paper, we extend the work of Lewis and Poole (2004) on the parametric bootstrap to DW-NOMINATE and obtain standard errors for the legislator ideal points. These standard errors are in the range of 1%–4% of the range of DW-NOMINATE coordinates.