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Recent changes to US research funding are having far-reaching consequences that imperil the integrity of science and the provision of care to vulnerable populations. Resisting these changes, the BJPsych Portfolio reaffirms its commitment to publishing mental science and advancing psychiatric knowledge that improves the mental health of one and all.
Preliminary evidence suggests that a ketogenic diet may be effective for bipolar disorder.
Aims
To assess the impact of a ketogenic diet in bipolar disorder on clinical, metabolic and magnetic resonance spectroscopy outcomes.
Method
Euthymic individuals with bipolar disorder (N = 27) were recruited to a 6- to 8-week single-arm open pilot study of a modified ketogenic diet. Clinical, metabolic and MRS measures were assessed before and after the intervention.
Results
Of 27 recruited participants, 26 began and 20 completed the ketogenic diet. For participants completing the intervention, mean body weight fell by 4.2 kg (P < 0.001), mean body mass index fell by 1.5 kg/m2 (P < 0.001) and mean systolic blood pressure fell by 7.4 mmHg (P < 0.041). The euthymic participants had average baseline and follow-up assessments consistent with them being in the euthymic range with no statistically significant changes in Affective Lability Scale-18, Beck Depression Inventory and Young Mania Rating Scale. In participants providing reliable daily ecological momentary assessment data (n = 14), there was a positive correlation between daily ketone levels and self-rated mood (r = 0.21, P < 0.001) and energy (r = 0.19 P < 0.001), and an inverse correlation between ketone levels and both impulsivity (r = −0.30, P < 0.001) and anxiety (r = −0.19, P < 0.001). From the MRS measurements, brain glutamate plus glutamine concentration decreased by 11.6% in the anterior cingulate cortex (P = 0.025) and fell by 13.6% in the posterior cingulate cortex (P = <0.001).
Conclusions
These findings suggest that a ketogenic diet may be clinically useful in bipolar disorder, for both mental health and metabolic outcomes. Replication and randomised controlled trials are now warranted.
Background: Cerebral venous thrombosis (CVT) is a rare cause of stroke, with 10–15% of patients experiencing dependence or death. The role of endovascular therapy (EVT) in the management of CVT remains controversial and practice patterns are not well-known. Methods: We distributed a comprehensive 53-question survey to neurologists, neuro-interventionalists, neurosurgeons and other relevant clinicians globally from May 2023 to October 2023. The survey asked about practice patterns and perspectives on EVT for CVT and assessed opinions regarding future clinical trials. Results: The overall response rate was 31% (863 respondents from 2744 invited participants) across 61 countries. A majority (74%) supported use of EVT for certain CVT cases. Key considerations for EVT included worsening level of consciousness (86%) and other clinical deficits (76%). Mechanical thrombectomy with aspiration (22%) and stent retriever (19%) were the most utilized techniques, with regional variations. Post-procedurally, low molecular weight heparin was the predominant anticoagulant administered (40%), although North American respondents favored unfractionated heparin. Most respondents supported future trials of EVT (90%). Conclusions: Our survey reveals significant heterogeneity in approaches to EVT for CVT, highlighting the necessity for adequately powered clinical trials to guide standard-of-care practices.
Recent evidence from case reports suggests that a ketogenic diet may be effective for bipolar disorder. However, no clinical trials have been conducted to date.
Aims
To assess the recruitment and feasibility of a ketogenic diet intervention in bipolar disorder.
Method
Euthymic individuals with bipolar disorder were recruited to a 6–8 week trial of a modified ketogenic diet, and a range of clinical, economic and functional outcome measures were assessed. Study registration number: ISRCTN61613198.
Results
Of 27 recruited participants, 26 commenced and 20 completed the modified ketogenic diet for 6–8 weeks. The outcomes data-set was 95% complete for daily ketone measures, 95% complete for daily glucose measures and 95% complete for daily ecological momentary assessment of symptoms during the intervention period. Mean daily blood ketone readings were 1.3 mmol/L (s.d. = 0.77, median = 1.1) during the intervention period, and 91% of all readings indicated ketosis, suggesting a high degree of adherence to the diet. Over 91% of daily blood glucose readings were within normal range, with 9% indicating mild hypoglycaemia. Eleven minor adverse events were recorded, including fatigue, constipation, drowsiness and hunger. One serious adverse event was reported (euglycemic ketoacidosis in a participant taking SGLT2-inhibitor medication).
Conclusions
The recruitment and retention of euthymic individuals with bipolar disorder to a 6–8 week ketogenic diet intervention was feasible, with high completion rates for outcome measures. The majority of participants reached and maintained ketosis, and adverse events were generally mild and modifiable. A future randomised controlled trial is now warranted.
The Amazon River dolphin Inia geoffrensis occurs throughout the basins of the Amazon and Orinoco Rivers and is categorized as Endangered on the IUCN Red List. Using satellite tracking data from eight dolphins (one female and seven males) in the Peruvian Amazon, we demonstrate that these dolphins inhabit a variety of habitat types and have core areas and home range areas of variable magnitudes. To gain a better understanding of how threats affect these dolphins, we examined the distance of dolphin records to locations of current and potential future anthropogenic threats. On average, dolphin home ranges overlapped with fisheries by 89%. Dolphins were found at an average distance of 252 km from the nearest proposed dam and 125 km from the nearest proposed dredging site. Given that many of these threats are still in the planning stage, we advise the government to consider the negative effects these activities have already had on other riverine species before proceeding. Additionally, efforts should be made to expand river dolphin tracking programmes to span multiple seasons, to track more females at our study sites and to increase the numbers tracked overall in other areas to improve our knowledge of the species' movement patterns.
New Zealand has a strategy of eliminating SARS-CoV-2 that has resulted in a low incidence of reported coronavirus-19 disease (COVID-19). The aim of this study was to describe the spread of SARS-CoV-2 in New Zealand via a nationwide serosurvey of blood donors. Samples (n = 9806) were collected over a month-long period (3 December 2020–6 January 2021) from donors aged 16–88 years. The sample population was geographically spread, covering 16 of 20 district health board regions. A series of Spike-based immunoassays were utilised, and the serological testing algorithm was optimised for specificity given New Zealand is a low prevalence setting. Eighteen samples were seropositive for SARS-CoV-2 antibodies, six of which were retrospectively matched to previously confirmed COVID-19 cases. A further four were from donors that travelled to settings with a high risk of SARS-CoV-2 exposure, suggesting likely infection outside New Zealand. The remaining eight seropositive samples were from seven different district health regions for a true seroprevalence estimate, adjusted for test sensitivity and specificity, of 0.103% (95% confidence interval, 0.09–0.12%). The very low seroprevalence is consistent with limited undetected community transmission and provides robust, serological evidence to support New Zealand's successful elimination strategy for COVID-19.
Ecosystem modeling, a pillar of the systems ecology paradigm (SEP), addresses questions such as, how much carbon and nitrogen are cycled within ecological sites, landscapes, or indeed the earth system? Or how are human activities modifying these flows? Modeling, when coupled with field and laboratory studies, represents the essence of the SEP in that they embody accumulated knowledge and generate hypotheses to test understanding of ecosystem processes and behavior. Initially, ecosystem models were primarily used to improve our understanding about how biophysical aspects of ecosystems operate. However, current ecosystem models are widely used to make accurate predictions about how large-scale phenomena such as climate change and management practices impact ecosystem dynamics and assess potential effects of these changes on economic activity and policy making. In sum, ecosystem models embedded in the SEP remain our best mechanism to integrate diverse types of knowledge regarding how the earth system functions and to make quantitative predictions that can be confronted with observations of reality. Modeling efforts discussed are the Century ecosystem model, DayCent ecosystem model, Grassland Ecosystem Model ELM, food web models, Savanna model, agent-based and coupled systems modeling, and Bayesian modeling.
Unit cohesion may protect service member mental health by mitigating effects of combat exposure; however, questions remain about the origins of potential stress-buffering effects. We examined buffering effects associated with two forms of unit cohesion (peer-oriented horizontal cohesion and subordinate-leader vertical cohesion) defined as either individual-level or aggregated unit-level variables.
Methods
Longitudinal survey data from US Army soldiers who deployed to Afghanistan in 2012 were analyzed using mixed-effects regression. Models evaluated individual- and unit-level interaction effects of combat exposure and cohesion during deployment on symptoms of post-traumatic stress disorder (PTSD), depression, and suicidal ideation reported at 3 months post-deployment (model n's = 6684 to 6826). Given the small effective sample size (k = 89), the significance of unit-level interactions was evaluated at a 90% confidence level.
Results
At the individual-level, buffering effects of horizontal cohesion were found for PTSD symptoms [B = −0.11, 95% CI (−0.18 to −0.04), p < 0.01] and depressive symptoms [B = −0.06, 95% CI (−0.10 to −0.01), p < 0.05]; while a buffering effect of vertical cohesion was observed for PTSD symptoms only [B = −0.03, 95% CI (−0.06 to −0.0001), p < 0.05]. At the unit-level, buffering effects of horizontal (but not vertical) cohesion were observed for PTSD symptoms [B = −0.91, 90% CI (−1.70 to −0.11), p = 0.06], depressive symptoms [B = −0.83, 90% CI (−1.24 to −0.41), p < 0.01], and suicidal ideation [B = −0.32, 90% CI (−0.62 to −0.01), p = 0.08].
Conclusions
Policies and interventions that enhance horizontal cohesion may protect combat-exposed units against post-deployment mental health problems. Efforts to support individual soldiers who report low levels of horizontal or vertical cohesion may also yield mental health benefits.
Introduction: The Cunningham reduction method for anterior shoulder dislocation offers an atraumatic alternative to traditional reduction techniques without the inconvenience and risk of procedural sedation and analgesia (PSA). Unfortunately, success rates as low as 27% have limited widespread use of this method. Inhaled methoxyflurane (I-MEOF) offers a rapidly administered, minimally invasive option for short-term analgesia. We conducted a pilot study to evaluate the feasibility of studying whether I-MEOF increased success rates for atraumatic reduction of anterior shoulder dislocation. Methods: A convenience sample of 20 patients with uncomplicated anterior shoulder dislocations were offered the Cunningham reduction method supported by methoxyflurane analgesia under the guidance of an advanced care paramedic. Operators were instructed to limit their attempt to the Cunningham method. Outcomes included success rate without the requirement for PSA, time to discharge, and operator and patient satisfaction with the procedure. Results: 20 patients received I-MEOF and an attempt at Cunningham reduction. 80% of patients were male, median age was 38.6 (range 18-71), and 55% were first dislocations of that joint. 35% (8/20 patients) had reduction successfully achieved by the Cunningham method under I-MEOF analgesia. The remainder proceeded to closed reduction under PSA. All patients had eventual successful reduction in the ED. 60% of operators reported good to excellent satisfaction with the process, with inadequate muscle relaxation being identified as the primary cause of failed initial attempts. 80% of patients reported good to excellent satisfaction. Conclusion: Success with the Cunningham technique was marginally increased with the use of I-MEOF, although 65% of patients still required PSA to facilitate reduction. The process was generally met with satisfaction by both providers and patients, suggesting that early administration of analgesia is appreciated. Moreover, one-third of patients had reduction achieved atraumatically without need for further intervention. A larger, randomized study may identify patient characteristics which make this reduction method more likely to be successful.
In product design engineering (PDE), ideation involves the generation of technical behaviours and physical structures to address specific functional requirements. This differs from generic creative ideation tasks, which emphasise functional and technical considerations less. To advance knowledge about the neural basis of PDE ideation, we present the first fMRI study on professional product design engineers practising in industry. We aimed to explore brain activation during ideation, and compare activation in open-ended and constrained tasks. Imagery manipulation tasks were contrasted with ideation tasks in a sample of 29 PDE professionals. The key findings were: (1) PDE ideation is associated with greater activity in left cingulate gyrus; (2) there were no significant differences between open-ended and constrained tasks; and (3) a preliminary association with activity in the right superior temporal gyrus was also observed. The results are consistent with existing fMRI work on generic creative ideation, suggesting that PDE ideation may share a number of similarities at the neural level. Future work includes: functional connectivity analysis of open-ended and constrained ideation to further investigate potential differences; investigating the effects of aspects of design expertise/training on processing; and the use of novelty measures directly linked to the designer’s internal processing in fMRI analysis.
Drug Safety Communications (DSCs) are used by the Food and Drug Administration (FDA) to inform health care providers, patients, caregivers, and the general public about safety issues related to FDA-approved drugs. To assess patient knowledge of the messaging contained in DSCs related to the sleep aids zolpidem and eszopiclone, we conducted a large, cross-sectional patient survey of 1,982 commercially insured patients selected by stratified random sampling from the Optum Research Database who had filled at least two prescriptions for either zolpidem or eszopiclone between July 1, 2012 and June 30, 2013. Among the 594 respondents (32.7% response rate), two-thirds reported hearing generally about drug safety information prior to starting a new drug, with the remaining one-third “rarely” or “never” hearing such information. Providers and pharmacists were primary sources of drug safety information. Two-thirds of zolpidem users and half of eszopiclone users reported having heard about the related DSC messages, ability to accurately identify the major factual messages was limited (overall median 2 correct out of 5, with men and those reporting higher educational level scoring higher [2/5 vs. 1/5, p=0.001]). Respondents reacted to new drug safety information about their sleep aids by reporting that they would want to learn about alternative ways to help them sleep (70%) and seek out more information about the safety of their specific sleeping pill (59-78%). Opportunities may exist for the FDA to work with providers and pharmacies to help ensure the DSC information is more widely received and is more fully understood by those taking the affected medications.
Background: SMA is characterized by reduced levels of survival of motor neuron (SMN) protein from deletions and/or mutations of the SMN1 gene. While SMN1 produces full-length SMN protein, a second gene, SMN2, produces low levels of functional SMN protein. Risdiplam (RG7916/RO7034067) is an investigational, orally administered, centrally and peripherally distributed small molecule that modulates pre-mRNA splicing of SMN2 to increase SMN protein levels. Methods: SUNFISH (NCT02908685) is an ongoing multicenter, double-blind, placebo-controlled, operationally seamless study (randomized 2:1, risdiplam:placebo) in patients aged 2–25 years, with Type 2/3 SMA. Part 1 (n=51) assesses safety, tolerability, pharmacokinetics and pharmacodynamics of different risdiplam dose levels. Pivotal Part 2 (n=180) assesses safety and efficacy of the risdiplam dose level selected based on Part 1 results. Results: Part 1 results showed a sustained, >2-fold increase in median SMN protein versus baseline following 1 year of treatment. Adverse events were mostly mild, resolved despite ongoing treatment and reflected underlying disease. No drug-related safety findings have led to withdrawal (data-cut 06/17/18). SUNFISH Part 1 exploratory endpoint results and Part 2 study design will also be presented. Conclusions: To date, no drug-related safety findings have led to withdrawal. Risdiplam led to sustained increases in SMN protein levels.
Whereas genetic susceptibility increases the risk for major depressive disorder (MDD), non-genetic protective factors may mitigate this risk. In a large-scale prospective study of US Army soldiers, we examined whether trait resilience and/or unit cohesion could protect against the onset of MDD following combat deployment, even in soldiers at high polygenic risk.
Methods
Data were analyzed from 3079 soldiers of European ancestry assessed before and after their deployment to Afghanistan. Incident MDD was defined as no MDD episode at pre-deployment, followed by a MDD episode following deployment. Polygenic risk scores were constructed from a large-scale genome-wide association study of major depression. We first examined the main effects of the MDD PRS and each protective factor on incident MDD. We then tested the effects of each protective factor on incident MDD across strata of polygenic risk.
Results
Polygenic risk showed a dose–response relationship to depression, such that soldiers at high polygenic risk had greatest odds for incident MDD. Both unit cohesion and trait resilience were prospectively associated with reduced risk for incident MDD. Notably, the protective effect of unit cohesion persisted even in soldiers at highest polygenic risk.
Conclusions
Polygenic risk was associated with new-onset MDD in deployed soldiers. However, unit cohesion – an index of perceived support and morale – was protective against incident MDD even among those at highest genetic risk, and may represent a potent target for promoting resilience in vulnerable soldiers. Findings illustrate the value of combining genomic and environmental data in a prospective design to identify robust protective factors for mental health.
Infants with prenatally diagnosed CHD are at high risk for adverse outcomes owing to multiple physiologic and psychosocial factors. Lack of immediate physical postnatal contact because of rapid initiation of medical therapy impairs maternal–infant bonding. On the basis of expected physiology, maternal–infant bonding may be safe for select cardiac diagnoses.
Methods
This is a single-centre study to assess safety of maternal–infant bonding in prenatal CHD.
Results
In total, 157 fetuses with prenatally diagnosed CHD were reviewed. On the basis of cardiac diagnosis, 91 fetuses (58%) were prenatally approved for bonding and successfully bonded, 38 fetuses (24%) were prenatally approved but deemed not suitable for bonding at delivery, and 28 (18%) were not prenatally approved to bond. There were no complications attributable to bonding. Those who successfully bonded were larger in weight (3.26 versus 2.6 kg, p<0.001) and at later gestation (39 versus 38 weeks, p<0.001). Those unsuccessful at bonding were more likely to have been delivered via Caesarean section (74 versus 49%, p=0.011) and have additional non-cardiac diagnoses (53 versus 29%, p=0.014). There was no significant difference regarding the need for cardiac intervention before hospital discharge. Infants who bonded had shorter hospital (7 versus 26 days, p=0.02) and ICU lengths of stay (5 versus 23 days, p=0.002) and higher survival (98 versus 76%, p<0.001).
Conclusion
Fetal echocardiography combined with a structured bonding programme can permit mothers and infants with select types of CHD to successfully bond before ICU admission and intervention.
Background: Spinal Muscular Atrophy (SMA) is an autosomal recessive neurodegenerative disease. In June 2017, Health Canada approved Nusinersen, currently the only available drug for SMA. Since 2016, patients in Ontario have been treated clinically with Nusinersen through different access programs. Methods: Retrospective case series of patients with SMA treated clinically with Nusinersen in Ontario, describing clinical characteristics and logistics of intrathecal Nusinersen administration. Results: Twenty patients have been treated across four centres. To date, we have reviewed 8 cases at one centre (seven SMA Type I, one SMA Type II). Age at first dose ranged from 3-156 months and disease duration 9-166 months. Patients had received 4-7 doses at last evaluation. Three patients with scoliosis (2 with spinal rods) required fluoroscopy-guided radiologist administration, and 4 required general anesthesia. No complications/adverse events were reported. At last follow up, 5/8 families reported improved daily activities. Of 5 patients with baseline and follow up motor function testing, 3 demonstrated improved scores. One patient died due to respiratory decline at age 9 months, despite improved motor outcome scores. Conclusions: We describe the first Canadian post-marketing experience with Nusinersen. Timely dissemination of this information is needed to guide clinicians, hospital administrators, and policy-makers.
The effect of transportation and lairage on the faecal shedding and post-slaughter contamination of carcasses with Escherichia coli O157 and O26 in young calves (4–7-day-old) was assessed in a cohort study at a regional calf-processing plant in the North Island of New Zealand, following 60 calves as cohorts from six dairy farms to slaughter. Multiple samples from each animal at pre-slaughter (recto-anal mucosal swab) and carcass at post-slaughter (sponge swab) were collected and screened using real-time PCR and culture isolation methods for the presence of E. coli O157 and O26 (Shiga toxin-producing E. coli (STEC) and non-STEC). Genotype analysis of E. coli O157 and O26 isolates provided little evidence of faecal–oral transmission of infection between calves during transportation and lairage. Increased cross-contamination of hides and carcasses with E. coli O157 and O26 between co-transported calves was confirmed at pre-hide removal and post-evisceration stages but not at pre-boning (at the end of dressing prior to chilling), indicating that good hygiene practices and application of an approved intervention effectively controlled carcass contamination. This study was the first of its kind to assess the impact of transportation and lairage on the faecal carriage and post-harvest contamination of carcasses with E. coli O157 and O26 in very young calves.
This collection of essays pays tribute to Nancy Freeman Regalado, a ground-breaking scholar in the field of medieval French literature whose research has always pushed beyond disciplinary boundaries. The articles in the volume reflect the depth and diversity of her scholarship, as well as her collaborations with literary critics, philologists, historians, art historians, musicologists, and vocalists - in France, England, and the United States. Inspired by her most recent work, these twenty-four essays are tied together by a single question, rich in ramifications: how does performance shape our understanding of medieval and pre-modern literature and culture, whether the nature of that performance is visual, linguistic, theatrical, musical, religious, didactic, socio-political, or editorial? The studies presented here invite us to look afresh at the interrelationship of audience, author, text, and artifact, to imagine new ways of conceptualizing the creation, transmission, and reception of medieval literature, music, and art.
EGLAL DOSS-QUINBY is Professor of French at Smith College; ROBERTA L. KRUEGER is Professor of French at Hamilton College; E. JANE BURNS is Professor of Women's Studies and Adjunct Professor of Comparative Literature at the University of North Carolina, Chapel Hill.
Contributors: ANNE AZÉMA, RENATE BLUMENFELD-KOSINSKI, CYNTHIA J. BROWN, ELIZABETH A. R. BROWN, MATILDA TOMARYN BRUCKNER, E. JANE BURNS, ARDIS BUTTERFIELD, KIMBERLEE CAMPBELL, ROBERT L. A. CLARK, MARK CRUSE, KATHRYN A. DUYS, ELIZABETH EMERY, SYLVIA HUOT, MARILYN LAWRENCE, KATHLEEN A. LOYSEN, LAURIE POSTLEWATE, EDWARD H. ROESNER, SAMUEL N. ROSENBERG, LUCY FREEMAN SANDLER, PAMELA SHEINGORN, HELEN SOLTERER, JANE H. M. TAYLOR, EVELYN BIRGE VITZ, LORI J. WALTERS, AND MICHEL ZINK.
To investigate an outbreak of Burkholderia cepacia complex and describe the measures that revealed the source.
SETTING
A 629-bed, tertiary-care, pediatric hospital in Houston, Texas.
PATIENTS
Pediatric patients without cystic fibrosis (CF) hospitalized in the pediatric and cardiovascular intensive care units.
METHODS
We investigated an outbreak of B. cepacia complex from February through July 2016. Isolates were evaluated for molecular relatedness with repetitive extragenic palindromic polymerase chain reaction (rep-PCR); specific species identification and genotyping were performed at an independent laboratory. The investigation included a detailed review of all cases, direct observation of clinical practices, and respiratory surveillance cultures. Environmental and product cultures were performed at an accredited reference environmental microbiology laboratory.
RESULTS
Overall, 18 respiratory tract cultures, 5 blood cultures, 4 urine cultures, and 3 stool cultures were positive in 24 patients. Among the 24 patients, 17 had symptomatic infections and 7 were colonized. The median age of the patients was 22.5 months (range, 2–148 months). Rep-PCR typing showed that 21 of 24 cases represented the same strain, which was identified as a novel species within the B. cepacia complex. Product cultures of liquid docusate were positive with an identical strain of B. cepacia complex. Local and state health departments, as well as the CDC and FDA, were notified, prompting a multistate investigation.
CONCLUSIONS
Our investigation revealed an outbreak of a unique strain of B. cepacia complex isolated in clinical specimens from non-CF pediatric patients and from liquid docusate. This resulted in a national alert and voluntary recall by the manufacturer.
A major question in ice-sheet dynamics is the state of balance between the net mass input and ice flow. Since an imbalance produces a change in surface elevation, the state of balance can be studied by monitoring the elevation, and this has been accomplished by surface-leveling techniques in a few locations. Due to the requirement for accurate and repetitive measurements over large areas, it is not practical to determine the status of balance of an entire ice sheet or even a major drainage basin by conventional techniques. Now, recent results from satellite-borne radar altimeter measurements over the Greenland ice sheet demonstrate the feasibility of accurately measuring and monitoring the topography of large ice masses. The application of this new technique offers the possibility of making a meaningful mass-balance determination and for detecting actual or potential ice-sheet surges.