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Bipolar depression remains difficult to treat, and people often experience ongoing residual symptoms, decreased functioning and impaired quality of life. Adjunctive therapies targeting novel pathways can provide wider treatment options and improve clinical outcomes. Garcinia mangostana Linn. (mangosteen) pericarp has serotonogenic, antioxidant anti-inflammatory and neurogenic properties of relevance to the mechanisms of bipolar depression.
Aims
The current 28-week randomised, multisite, double-blind, placebo-controlled trial investigated mangosteen pericarp extract as an adjunct to treatment-as-usual for treatment of bipolar depression.
Method
This trial was prospectively registered on the Australia New Zealand Clinical Trials Registry (no. ACTRN12616000028404). Participants aged 18 years and older with a diagnosis of bipolar I or II and with at least moderate depressive symptoms were eligible for the study. A total of 1016 participants were initially approached or volunteered for the study, of whom 712 did not progress to screening, with an additional 152 screened out. Seventy participants were randomly allocated to mangosteen and 82 to a placebo control. Fifty participants in the mangosteen and 64 participants in the placebo condition completed the treatment period and were analysed.
Results
Results indicated limited support for the primary hypothesis of superior depression symptom reduction following 24 weeks of treatment. Although overall changes in depressive symptoms did not substantially differ between conditions over the course of the trial, we observed significantly greater improvements for the mangosteen condition at 24 weeks, compared with baseline, for mood symptoms, clinical impressions of bipolar severity and social functioning compared with controls. These differences were attenuated at week 28 post-discontinuation assessment.
Conclusions
Adjunctive mangosteen pericarp treatment appeared to have limited efficacy in mood and functional symptoms associated with bipolar disorder, but not with manic symptoms or quality of life, suggesting a novel therapeutic approach that should be verified by replication.
Childhood sexual abuse (CSA) and emotional maltreatment are salient risk factors for the development of major depressive disorder (MDD) in women. However, the type- and timing-specific effects of emotional maltreatment experienced during adolescence on future depressive symptomatology in women with CSA have not been explored. The goal of this study was to fill this gap.
Methods
In total, 203 women (ages 20–32) with current depressive symptoms and CSA (MDD/CSA), remitted depressive symptoms and CSA (rMDD/CSA), and current depressive symptoms without CSA (MDD/no CSA) were recruited from the community and completed self-report measures. Depressive symptoms were assessed using the Beck Depression Inventory (BDI-II) and a detailed maltreatment history was collected using the Maltreatment and Abuse Chronology of Exposure (MACE). Differences in maltreatment exposure characteristics, including multiplicity and severity of maltreatment, as well as the chronologies of emotional maltreatment subtypes were compared among groups. A random forest machine-learning algorithm was utilized to assess the impact of exposure to emotional maltreatment subtypes at specific ages on current depressive symptoms.
Results
MDD/CSA women reported greater prevalence and severity of emotional maltreatment relative to rMDD/CSA and MDD/no CSA women [F(2,196) = 9.33, p < 0.001], specifically from ages 12 to 18. The strongest predictor of current depressive symptoms was parental verbal abuse at age 18 for both MDD/CSA women (variable importance [VI] = 1.08, p = 0.006) and MDD/no CSA women (VI = 0.68, p = 0.004).
Conclusions
Targeting emotional maltreatment during late adolescence might prove beneficial for future intervention efforts for MDD following CSA.
Solid-state nuclear magnetic resonance (NMR) spectroscopy, thermal analysis, and X-ray powder diffraction data on the tubular, hydrous aluminosilicate imogolite were found to be fully consistent with a previously proposed crystal structure consisting of a rolled-up, 6-coordinate Al-O(OH) sheet, bonded to isolated orthosilicate groups. The calculated 29Si chemical shift of this structure agreed with the observed shift within 3 ppm. Thermal dehydroxylation of the Al-O(OH) sheet produced predominantly NMR-transparent 5-coordinate Al, but a few 4- and 6-coordinate sites and some residual hydroxyl groups may also have formed, as shown by NMR spectroscopy. Changes in the 29Si NMR spectrum on dehydroxylation suggest a condensation of the orthosilicate groups, but steric considerations rule out bonding between adjacent silicons. To account for these observations, an alternative mechanism to orthosilicate condensation has been proposed, involving the fracture and unrolling of the tubes, followed by the condensation of fragments to form a layer structure. The layer structure has a calculated 29Si chemical shift of -95.6 ppm, in good agreement with the observed value of -93 ppm.
To investigate the symptoms of SARS-CoV-2 infection, their dynamics and their discriminatory power for the disease using longitudinally, prospectively collected information reported at the time of their occurrence. We have analysed data from a large phase 3 clinical UK COVID-19 vaccine trial. The alpha variant was the predominant strain. Participants were assessed for SARS-CoV-2 infection via nasal/throat PCR at recruitment, vaccination appointments, and when symptomatic. Statistical techniques were implemented to infer estimates representative of the UK population, accounting for multiple symptomatic episodes associated with one individual. An optimal diagnostic model for SARS-CoV-2 infection was derived. The 4-month prevalence of SARS-CoV-2 was 2.1%; increasing to 19.4% (16.0%–22.7%) in participants reporting loss of appetite and 31.9% (27.1%–36.8%) in those with anosmia/ageusia. The model identified anosmia and/or ageusia, fever, congestion, and cough to be significantly associated with SARS-CoV-2 infection. Symptoms’ dynamics were vastly different in the two groups; after a slow start peaking later and lasting longer in PCR+ participants, whilst exhibiting a consistent decline in PCR- participants, with, on average, fewer than 3 days of symptoms reported. Anosmia/ageusia peaked late in confirmed SARS-CoV-2 infection (day 12), indicating a low discrimination power for early disease diagnosis.
Ultra-processed plant-based foods, such as plant-based burgers, have gained in popularity. Particularly in the out-of-home (OOH) environment, evidence regarding their nutritional profile and environmental sustainability is still evolving. Plant-based burgers available at selected OOH sites were randomly sampled in Amsterdam, Copenhagen, Lisbon and London. Plant-based burgers (patty, bread and condiment) (n 41) were lab analysed for their energy, macronutrients, amino acids and minerals content per 100 g and serving and were compared with reference values. For the plant-based burgers, the median values per 100 g were 234 kcal, 20·8 g carbohydrates, 3·5 g dietary fibre and 12·0 g fat, including 0·08 g TFS and 2·2 g SFA. Protein content was 8·9 g/100 g, with low protein quality according to amino acid composition. Median Na content was 389 mg/100 g, equivalent to 1 g salt. Compared with references, the median serving provided 31% of energy intake based on a 2000 kcal per day and contributed to carbohydrates (17–28%), dietary fibre (42%), protein (40%), total fat (48%), SFA (26%) and Na (54%). One serving provided 15–23% of the reference values for Ca, K and Mg, while higher contributions were found for Zn, Mn, P and Fe (30–67%). The ultra-processed plant-based burgers provide protein, dietary fibre and essential minerals and contain relatively high levels of energy, Na and total fats. The amino acid composition indicated low protein quality. The multifaceted nutritional profile of plant-based burgers highlights the need for manufacturers to implement improvements to better support healthy dietary habits, including reducing energy, Na and total fats.
This poster will explore the experiences of three junior doctors during their inpatient psychiatry placements. These doctors are Foundation Year 1, Foundation Year 2, and Foundation Year 3 doctors - i.e. not psychiatry trainees.
Objectives
Due to the nature of the UK Foundation Programme, many FY doctors will not have chosen to work in psychiatry and will have been given the rotation as part of a package of jobs. Studies have shown that the risk of burnout is higher when a doctor working in psychiatry did not identify it as their top career choice (Jovanović, N. et al. (2016) European Psychiatry, 32, pp. 34–41). Lack of supervision is also a risk factor for burnout (Jovanović, N. et al. (2016) European Psychiatry, 32, pp. 34–41).
A phenomenological study(Beattie, S. et al. (2017) BMJ Open, 7(9)) demonstrated that job satisfaction and morale amongst junior doctors in psychiatry can be positively influenced by a sense of connectedness, clear role definition, structure and appropriate responsibility. Additionally, junior doctors’ experience of psychiatry, positive or negative, can influence their future career plans (Stott, J., Haywood, J. and Crampton, P. (2021) 43(10), pp. 1196–1202); this has important implications for recruitment into the specialty.
Methods
Three junior doctors were interviewed. These consisted of two Foundation Year doctors, and one doctor who has completed FY2 but is working as a locum and not currently in training. They were asked about memorable experiences during their psychiatry placements. Additionally, they were asked about their emotions regarding work at the very start of their placements and towards the end.
Results
The junior doctors that participated in interviews for the poster initially found the psychiatric inpatient setting challenging and overwhelming. Some of the challenges focused on the occasionally violent and risky nature of the ward and adjusting to that environment. However, all three doctors were pleasantly surprised by the way they adapted to the ward, the supportive nature of the team, and the rewarding experience of seeing very unwell patients get better.
Conclusions
Overall the interviews demonstrated that there is a significant emotional impact on junior doctors working in psychiatry, particularly when it is their first experience of in-patient psychiatry. However, this emotional demand can be mitigated by a supportive multi-disciplinary team and good quality supervision.
An experiment was conducted to investigate the incidence of travel sickness in pigs, specific hormone concentrations at exsanguination and subsequent meat quality. Fifty, 80kg slaughter pigs were transported on a lorry for 4.5h. During the journey, behavioural observations of the individually marked pigs were made by scanning every 8min to establish whether the pigs exhibited certain symptoms of travel sickness (foaming at the mouth and chomping) and incidences of retching and vomiting were noted as they occurred. Upon arrival at the slaughterhouse, pigs were unloaded, slaughtered immediately and a blood sample was taken at exsanguination for analysis of plasma Cortisol, beta-endorphin and lysine vasopressin concentrations. On the day following slaughter, the chilled carcase of each pig was assessed for meat quality (using pH, Fibre Optic Probe, and Tecpro Pork Quality Meter measurements) in the longissimus dorsi, semimembranosus and adductor muscles to determine the incidence of PSE (pale, soft, exudative) or DFD (dark, firm, dry) meat quality. Twenty-six per cent of the pigs (a total of 13 individuals) vomited or retched during the journey. There was no relationship between the incidence of travel sickness and either the concentrations of the hormones analysed at exsanguination or subsequent meat quality. Correlations revealed no significant relationship between concentrations of the hormones and meat quality measurements.
The question of whether witnessing slaughter of conspecifics is distressing was investigated in sheep. Previously catheterized sheep were allowed to see the stunning and sticking (exsanguination) of other sheep. Heart rate was monitored and serial blood samples were taken to assess stress responses. Although the measurable parameter levels were generally high due to human contact and handling, there were no specific increases in response to witnessing stunning and slaughter. This work failed to produce any evidence to suggest that sheep are distressed by witnessing the slaughter act.
Humpback whales (Megaptera novaeangliae) exhibit maternally driven fidelity to feeding grounds, and yet occasionally occupy new areas. Humpback whale sightings and mortalities in the New York Bight apex (NYBA) have been increasing over the last decade, providing an opportunity to study this phenomenon in an urban habitat. Whales in this area overlap with human activities, including busy shipping traffic leading into the Port of New York and New Jersey. The site fidelity, population composition and demographics of individual whales were analysed to better inform management in this high-risk area. Whale watching and other opportunistic data collections were used to identify 101 individual humpback whales in the NYBA from spring through autumn, 2012–2018. Although mean occurrence was low (2.5 days), mean occupancy was 37.6 days, and 31.3% of whales returned from one year to the next. Individuals compared with other regional and ocean-basin-wide photo-identification catalogues (N = 52) were primarily resighted at other sites along the US East Coast, including the Gulf of Maine feeding ground. Sightings of mother-calf pairs were rare in the NYBA, suggesting that maternally directed fidelity may not be responsible for the presence of young whales in this area. Other factors including shifts in prey species distribution or changes in population structure more broadly should be investigated.
COVID-19 is a major health threat around the world causing hundreds of millions of infections and millions of deaths. There is a pressing global need for effective therapies. We hypothesized that leukotriene inhibitors (LTIs), that have been shown to lower IL6 and IL8 levels, may have a protective effect in patients with COVID-19.
Methods:
In this retrospective controlled cohort study, we compared death rates in COVID-19 patients who were taking a LTI with those who were not taking an LTI. We used the Department of Veterans Affairs (VA) Corporate Data Warehouse (CDW) to create a cohort of COVID-19-positive patients and tracked their use of LTIs between November 1, 2019 and November 11, 2021.
Results:
Of the 1,677,595 cohort of patients tested for COVID-19, 189,195 patients tested positive for COVID-19. Forty thousand seven hundred one were admitted. 38,184 had an oxygen requirement and 1214 were taking an LTI. The use of dexamethasone plus a LTI in hospital showed a survival advantage of 13.5% (CI: 0.23%–26.7%; p < 0.01) in patients presenting with a minimal O2Sat of 50% or less. For patients with an O2Sat of <60 and <50% if they were on LTIs as outpatients, continuing the LTI led to a 14.4% and 22.25 survival advantage if they were continued on the medication as inpatients.
Conclusions:
When combined dexamethasone and LTIs provided a mortality benefit in COVID-19 patients presenting with an O2 saturations <50%. The LTI cohort had lower markers of inflammation and cytokine storm.
Background: Medulloblastoma (MB) is the most common solid malignant pediatric brain neoplasm. Group 3 (G3) MB, particularly MYC amplified G3 MB, is the most aggressive subgroup with the highest frequency of children presenting with metastatic disease, and is associated with a poor prognosis. To further our understanding of the role of MSI1 in MYC amplified G3 MB, we performed an unbiased integrative analysis of eCLIP binding sites, with changes observed at the transcriptome, the translatome, and the proteome after shMSI1 inhibition. Methods: Primary human pediatric MBs, SU_MB002 and HD-MB03 were kind gifts from Dr. Yoon-Jae Cho (Harvard, MS) and Dr. Till Milde (Heidelberg) and cultured for in vitro and in vivo experiments. eCLIP, RNA-seq, Polysome-seq, and TMT-MS were completed as previously described. Results:MSI1 is overexpressed in G3 MB. shRNA Msi1 interference resulted in a reduction in tumour burden conferring a survival advantage to mice injected with shMSI1 G3MB cells. Robust ranked multiomic analysis (RRA) identified an unconventional gene set directly perturbed by MSI1 in G3 MB. Conclusions: Our robust unbiased integrative analysis revealed a distinct role for MSI1 in the maintenance of the stem cell state in G3 MB through post-transcriptional modification of multiple pathways including identification of unconventional targets such as HIPK1.
This study aimed to investigate whether children with cochlear implants received the recommended vaccinations according to New Zealand national immunisation guidelines and to report the incidence of meningitis in this population after intervention.
Method
A retrospective review of the vaccination coverage of paediatric patients receiving cochlear implants between 2005 and 2019 was performed.
Results
Data were collected on 203 children. Evidence of immunisation against Haemophilus influenza B was documented in 94.1 per cent of this cohort and 21.2 per cent received the seasonal influenza vaccine. The pneumococcal conjugate vaccine was fully administered in 81.8 per cent of children; however, only 16.9 per cent of eligible children had received the pneumococcal polysaccharide vaccine. There was marked improvement in compliance to the pneumococcal conjugate vaccine once it became fully funded for cochlear implant patients.
Conclusion
Despite established guidelines, the paediatric vaccination rates were less than expected. Work is in progress to address this.
We present the data and initial results from the first pilot survey of the Evolutionary Map of the Universe (EMU), observed at 944 MHz with the Australian Square Kilometre Array Pathfinder (ASKAP) telescope. The survey covers $270 \,\mathrm{deg}^2$ of an area covered by the Dark Energy Survey, reaching a depth of 25–30 $\mu\mathrm{Jy\ beam}^{-1}$ rms at a spatial resolution of $\sim$11–18 arcsec, resulting in a catalogue of $\sim$220 000 sources, of which $\sim$180 000 are single-component sources. Here we present the catalogue of single-component sources, together with (where available) optical and infrared cross-identifications, classifications, and redshifts. This survey explores a new region of parameter space compared to previous surveys. Specifically, the EMU Pilot Survey has a high density of sources, and also a high sensitivity to low surface brightness emission. These properties result in the detection of types of sources that were rarely seen in or absent from previous surveys. We present some of these new results here.
Typical enteropathogenic Escherichia coli (tEPEC) infection is a major cause of diarrhoea and contributor to mortality in children <5 years old in developing countries. Data were analysed from the Global Enteric Multicenter Study examining children <5 years old seeking care for moderate-to-severe diarrhoea (MSD) in Kenya. Stool specimens were tested for enteric pathogens, including by multiplex polymerase chain reaction for gene targets of tEPEC. Demographic, clinical and anthropometric data were collected at enrolment and ~60-days later; multivariable logistic regressions were constructed. Of 1778 MSD cases enrolled from 2008 to 2012, 135 (7.6%) children tested positive for tEPEC. In a case-to-case comparison among MSD cases, tEPEC was independently associated with presentation at enrolment with a loss of skin turgor (adjusted odds ratio (aOR) 2.08, 95% confidence interval (CI) 1.37–3.17), and convulsions (aOR 2.83, 95% CI 1.12–7.14). At follow-up, infants with tEPEC compared to those without were associated with being underweight (OR 2.2, 95% CI 1.3–3.6) and wasted (OR 2.5, 95% CI 1.3–4.6). Among MSD cases, tEPEC was associated with mortality (aOR 2.85, 95% CI 1.47–5.55). This study suggests that tEPEC contributes to morbidity and mortality in children. Interventions aimed at defining and reducing the burden of tEPEC and its sequelae should be urgently investigated, prioritised and implemented.
Gravitational waves from coalescing neutron stars encode information about nuclear matter at extreme densities, inaccessible by laboratory experiments. The late inspiral is influenced by the presence of tides, which depend on the neutron star equation of state. Neutron star mergers are expected to often produce rapidly rotating remnant neutron stars that emit gravitational waves. These will provide clues to the extremely hot post-merger environment. This signature of nuclear matter in gravitational waves contains most information in the 2–4 kHz frequency band, which is outside of the most sensitive band of current detectors. We present the design concept and science case for a Neutron Star Extreme Matter Observatory (NEMO): a gravitational-wave interferometer optimised to study nuclear physics with merging neutron stars. The concept uses high-circulating laser power, quantum squeezing, and a detector topology specifically designed to achieve the high-frequency sensitivity necessary to probe nuclear matter using gravitational waves. Above 1 kHz, the proposed strain sensitivity is comparable to full third-generation detectors at a fraction of the cost. Such sensitivity changes expected event rates for detection of post-merger remnants from approximately one per few decades with two A+ detectors to a few per year and potentially allow for the first gravitational-wave observations of supernovae, isolated neutron stars, and other exotica.
OBJECTIVES/GOALS: Utilize polymer-based fiber scaffolds and machine learning methods applied to patient biomarker data to enhance and personalize T cell expansion and production for T cell therapy in chronic lymphocytic leukemia. METHODS/STUDY POPULATION: Scaffolds are 1) generated from a co-polymer blend of PDMS and PCL with controlled fiber diameters and pore size, 2) coated with activating antibodies to CD3 and CD28, and 3) used to stimulate T cells from both healthy donors and CLL patients. CLL patients have pre-annotated mutation burdens and clinical biomarkers. T cell populations will be analyzed for exhaustion markers and phenotypes before, during, and after expansion. Cell functionality will be measured by cytokine secretion, cell cycle analysis, and fold expansion, with respect to platform parameters, and analyzed with inputs of disease markers and exhaustion profile of isolated T cells using regression and random forest classifiers. RESULTS/ANTICIPATED RESULTS: We previously showed that engineering the mechanical rigidity of activating substrates can enhance and rescue T cell expansion from exhausted populations. Now we aim to study a broader range of compositions and geometry of scaffolds with respect to capacity to expand CLL T cells. Preliminary data with fiber diameters ranging from 300 nm to 6 um confirm the effect of geometry in modulating expansion. A biorepository of T cells from 80 CLL patients have been isolated concurrently. Anticipated results include correlating exhaustion profile of T cells with clinical biomarkers and identifying markers associated with expansion on panel of platform parameters. DISCUSSION/SIGNIFICANCE OF IMPACT: T cell therapy has shown particular promise in treating blood cancers, yet significant percentage of T cells isolated from patients undergoing treatments are unresponsive to activation. A powerful tool is to predict if and how patient T cells can be robustly expanded on a personalized approach.
The National Institute of Standards and Technology (NIST) certifies a suite of Standard Reference Materials (SRMs) to evaluate specific aspects of instrument performance of both X-ray and neutron powder diffractometers. This report describes SRM 660c, the fourth generation of this powder diffraction SRM, which is used primarily for calibrating powder diffractometers with respect to line position and line shape for the determination of the instrument profile function (IPF). It is certified with respect to lattice parameter and consists of approximately 6 g of lanthanum hexaboride (LaB6) powder. So that this SRM would be applicable for the neutron diffraction community, the powder was prepared from an isotopically enriched 11B precursor material. The microstructure of the LaB6 powder was engineered specifically to yield a crystallite size above that where size broadening is typically observed and to minimize the crystallographic defects that lead to strain broadening. A NIST-built diffractometer, incorporating many advanced design features, was used to certify the lattice parameter of the LaB6 powder. Both Type A, statistical, and Type B, systematic, uncertainties have been assigned to yield a certified value for the lattice parameter at 22.5 °C of a = 0.415 682 6 ± 0.000 008 nm (95% confidence).
Limited research considers the ethnic and cultural diversity among the US Black population, and how this diversity influences diet. The purpose of the present qualitative study is to (1) explore the influence of culture, nativity and ethnicity on the diet of US-born, African-born and Caribbean/Latin American-born Blacks and (2) explore a model of dietary acculturation among the African-born and Caribbean/Latin American-born Blacks. The purposive sample included twenty-two US-born, fifteen Caribbean/Latin American-born and ten African-born Blacks (n 47) living in Boston, who participated in either an in-depth interview (n 12) or a focus group (five groups, size 5–9). Satia-Abouta's model of dietary acculturation informed the interview and focus group questions, which explored the influence of psychosocial factors, taste preferences and environmental factors on dietary changes. NVivo 10 software was utilised for the coding and analysis. Topics based on a priori and posteriori analyses included differences in psychosocial factors and taste preferences and environmental factors by nativity. Caribbean/Latin American-born and African-born Blacks expressed the importance of cultural identity in their dietary preferences and found adaptive strategies to maintain cultural diet, while US-born Blacks demonstrated a variety of preferences for traditionally African American foods. Environmental factors varied by place of birth and residence, with US-born Blacks citing poorer quality and limited affordability of foods. These findings suggest the importance of psychosocial and environmental factors in shaping the diet of the ethnically diverse US Black population and underscore the dietary diversity within and across the different ethnic groups of Blacks.