Revealing uncertainty in the status of biodiversity change.

Biodiversity faces unprecedented threats from rapid global change1. Signals of biodiversity change come from time-series abundance datasets for thousands of species over large geographic and temporal scales. Analyses of these biodiversity datasets have pointed to varied trends in abundance, including increases and decreases. However, these analyses have not fully accounted for spatial, temporal and phylogenetic structures in the data. Here, using a new statistical framework, we show across ten high-profile biodiversity datasets2-11 that increases and decreases under existing approaches vanish once spatial, temporal and phylogenetic structures are accounted for. This is a consequence of existing approaches severely underestimating trend uncertainty and sometimes misestimating the trend direction. Under our revised average abundance trends that appropriately recognize uncertainty, we failed to observe a single increasing or decreasing trend at 95% credible intervals in our ten datasets. This emphasizes how little is known about biodiversity change across vast spatial and taxonomic scales. Despite this uncertainty at vast scales, we reveal improved local-scale prediction accuracy by accounting for spatial, temporal and phylogenetic structures. Improved prediction offers hope of estimating biodiversity change at policy-relevant scales, guiding adaptive conservation responses.

Variation in the clinical management of self-harm by area-level socio-economic deprivation: findings from the multicenter study of self-harm in England.

BACKGROUND: We investigated disparities in the clinical management of self-harm following hospital presentation with self-harm according to level of socio-economic deprivation (SED) in England. METHODS: 108 092 presentations to hospitals (by 57 306 individuals) after self-harm in the Multicenter Study of Self-harm spanning 17 years. Area-level SED was based on the English Index of Multiple Deprivation. Information about indicators of clinical care was obtained from each hospital's self-harm monitoring systems. We assessed the associations of SED with indicators of care using mixed effect models. RESULTS: Controlling for confounders, psychosocial assessment and admission to a general medical ward were less likely for presentations by patients living in more deprived areas relative to presentations by patients from the least deprived areas. Referral for outpatient mental health care was less likely for presentations by patients from the two most deprived localities (most deprived: adjusted odd ratio [aOR] 0.77, 95% CI 0.71-0.83, p < 0.0001; 2nd most deprived: aOR 0.80, 95% CI 0.74-0.87, p < 0.0001). Referral to substance use services and 'other' services increased with increased SED. Overall, referral for aftercare was less likely following presentations by patients living in the two most deprived areas (most deprived: aOR 0.85, 95% CI 0.78-0.92, p < 0.0001; 2nd most deprived: aOR 0.86, 95% CI 0.79-0.94, p = 0.001). CONCLUSIONS: SED is associated with differential care for patients who self-harm in England. Inequalities in care may exacerbate the risk of adverse outcomes in this disadvantaged population. Further work is needed to understand the reasons for these differences and ways of providing more equitable care.

Prenatal antidepressant exposure is associated with risk for attention-deficit hyperactivity disorder but not autism spectrum disorder in a large health system.

Previous studies suggested that risk for Autism Spectrum Disorder (ASD) may be increased in children exposed to antidepressants during the prenatal period. The disease specificity of this risk has not been addressed and the possibility of confounding has not been excluded. Children with ASD or attention-deficit hyperactivity disorder (ADHD) delivered in a large New England health-care system were identified from electronic health records (EHR), and each diagnostic group was matched 1:3 with children without ASD or ADHD. All children were linked with maternal health data using birth certificates and EHRs to determine prenatal medication exposures. Multiple logistic regression was used to examine association between prenatal antidepressant exposures and ASD or ADHD risk. A total of 1377 children diagnosed with ASD and 2243 with ADHD were matched with healthy controls. In models adjusted for sociodemographic features, antidepressant exposure prior to and during pregnancy was associated with ASD risk, but risk associated with exposure during pregnancy was no longer significant after controlling for maternal major depression (odds ratio (OR) 1.10 (0.70-1.70)). Conversely, antidepressant exposure during but not prior to pregnancy was associated with ADHD risk, even after adjustment for maternal depression (OR 1.81 (1.22-2.70)). These results suggest that the risk of autism observed with prenatal antidepressant exposure is likely confounded by severity of maternal illness, but further indicate that such exposure may still be associated with ADHD risk. This risk, modest in absolute terms, may still be a result of residual confounding and must be balanced against the substantial consequences of untreated maternal depression.

Revisiting the phylogeography and demography of European badgers (Meles meles) based on broad sampling, multiple markers and simulations.

Although the phylogeography of European mammals has been extensively investigated since the 1990s, many studies were limited in terms of sampling distribution, the number of molecular markers used and the analytical techniques employed, frequently leading to incomplete postglacial recolonisation scenarios. The broad-scale genetic structure of the European badger (Meles meles) is of interest as it may result from historic restriction to glacial refugia and/or recent anthropogenic impact. However, previous studies were based mostly on samples from western Europe, making it difficult to draw robust conclusions about the location of refugia, patterns of postglacial expansion and recent demography. In the present study, continent-wide sampling and analyses with multiple markers provided evidence for two glacial refugia (Iberia and southeast Europe) that contributed to the genetic variation observed in badgers in Europe today. Approximate Bayesian computation provided support for a colonisation of Scandinavia from both Iberian and southeastern refugia. In the whole of Europe, we observed a decline in genetic diversity with increasing latitude, suggesting that the reduced diversity in the peripheral populations resulted from a postglacial expansion processes. Although MSVAR v.1.3 also provided evidence for recent genetic bottlenecks in some of these peripheral populations, the simulations performed to estimate the method's power to correctly infer the past demography of our empirical populations suggested that the timing and severity of bottlenecks could not be established with certainty. We urge caution against trying to relate demographic declines inferred using MSVAR with particular historic or climatological events.

Suicide in bipolar disorder in a national English sample, 1996-2009: frequency, trends and characteristics.

BACKGROUND: Bipolar disorder (BD) has been reported to be associated with high risk of suicide. We aimed to investigate the frequency and characteristics of suicide in people with BD in a national sample. METHOD: Suicide in BD in England from 1996 to 2009 was explored using descriptive statistics on data collected by the National Confidential Inquiry into Suicide and Homicide by People with Mental Illness (NCI). Suicide cases with a primary diagnosis of BD were compared to suicide cases with any other primary diagnosis. RESULTS: During the study period 1489 individuals with BD died by suicide, an average of 116 cases/year. Compared to other primary diagnosis suicides, those with BD were more likely to be female, more than 5 years post-diagnosis, current/recent in-patients, to have more than five in-patient admissions, and to have depressive symptoms. In BD suicides the most common co-morbid diagnoses were personality disorder and alcohol dependence. Approximately 40% were not prescribed mood stabilizers at the time of death. More than 60% of BD suicides were in contact with services the week prior to suicide but were assessed as low risk. CONCLUSIONS: Given the high rate of suicide in BD and the low estimates of risk, it is important that health professionals can accurately identify patients most likely to experience poor outcomes. Factors such as alcohol dependence/misuse, personality disorder, depressive illness and current/recent in-patient admission could characterize a high-risk group. Future studies need to operationalize clinically useful indicators of suicide risk in BD.

Global control of hepatitis B virus: does treatment-induced antigenic change affect immunization?

Since its widespread introduction, the hepatitis B vaccine has become an essential part of infant immunization programmes globally. The vaccine has been particularly important for countries where the incidence of hepatitis B virus-related hepatocellular carcinoma is high. Effective treatment options for individuals with chronic hepatitis B infection were limited until 1998 when lamivudine, the first nucleoside analogue drug, was introduced. As a single treatment agent, however, lamivudine has a significant drawback: it induces lamivudine-resistant hepatitis B virus strains that may pose a risk to the global hepatitis B immunization programme. Mutations associated with drug treatment can cause changes to the surface antigen protein, the precise part of the virus that the hepatitis B vaccine mimics. However, the emergence of antiviral drug-associated potential vaccine escape mutants (ADAP-VEMs) in treated patients does not necessarily pose a significant, imminent threat to the global hepatitis B immunization programme. Nonetheless, there is already evidence that current treatment regimens have resulted in the selection of stable ADAP-VEMs. Treatment is currently intended to prevent the long-term complications of hepatitis B virus infection, with little consideration given to potential adverse public health impacts. To address individual and public health concerns, trials are urgently needed to find the optimal combination of existing drugs that are effective but do not induce the emergence of ADAP-VEMs. This paper examines the mechanism of antiviral drug-selected changes in the portion of the viral genome that also affects the surface antigen, and explores their potential impact on current hepatitis B immunization programmes.

Effect of time series length and resolution on abundance- and trait-based early warning signals of population declines.

Natural populations are increasingly threatened with collapse at the hands of anthropogenic effects. Predicting population collapse with the help of generic early warning signals (EWS) may provide a prospective tool for identifying species or populations at highest risk. However, pattern-to-process methods such as EWS have a multitude of challenges to overcome to be useful, including the low signal-to-noise ratio of ecological systems and the need for high quality time series data. The inclusion of trait dynamics with EWS has been proposed as a more robust tool to predict population collapse. However, the length and resolution of available time series are highly variable from one system to another, especially when generation time is considered. As yet, it remains unknown how this variability with regards to generation time will alter the efficacy of EWS. Here we take both a simulation- and experimental-based approach to assess the impacts of relative time series length and resolution on the forecasting ability of EWS. We show that EWS' performance decreases with decreasing time-series length. However, there was no evident decrease in EWS performance as resolution decreased. Our simulations suggest a relative time series length between 10 and five generations as a minimum requirement for accurate forecasting by abundance-based EWS. However, when trait information is included alongside abundance-based EWS, we find positive signals at lengths one-half of what was required without them. We suggest that, in systems where specific traits are known to affect demography, trait data should be monitored and included alongside abundance data to improve forecasting reliability.

The major histocompatibility complex class Ib molecule HLA-E at the interface between innate and adaptive immunity.

The non-classical major histocompatibility complex (MHC) class I molecule human leucocyte antigen (HLA)-E is the least polymorphic of all the MHC class I molecules and acts as a ligand for receptors of both the innate and the adaptive immune systems. The recognition of self-peptides complexed to HLA-E by the CD94-NKG2A receptor expressed by natural killer (NK) cells represents a crucial checkpoint for immune surveillance by NK cells. However, HLA-E can also be recognised by the T-cell receptor expressed by alphabeta CD8 T cells and therefore can play a role in the adaptive immune response to invading pathogens. The recent resolution of HLA-E in complex with both innate and adaptive ligands has provided insight into the dual role of this molecule in immunity.

A review of measles supplementary immunization activities and the implications for Pacific Island countries and territories.

INTRODUCTION: Standard measles control strategies include achieving high levels of measles vaccine coverage using routine delivery systems, supplemented by mass immunization campaigns as needed to close population immunity gaps. Areas covered: This review looks at how supplementary immunization activities (SIAs) have contributed to measles control globally, and asks whether such a strategy has a place in Pacific Islands today. Expert commentary: Very high coverage with two doses of measles vaccine seems to be the optimal strategy for controlling measles. By 2015, all but two Pacific Islands had introduced a second dose in the routine schedule; however, a number of countries have not yet reached high coverage with their second dose. The literature and the country reviews reported here suggest that a high coverage SIA combined with one dose of measles vaccine given in the routine system will also do the job. The arguments for and against the use of SIAs are complex, but it is clear that to be effective, SIAs need to be well designed to meet specific needs, must be carried out effectively and safely with very high coverage, and should, when possible, carry with them other public health interventions to make them even more cost-effective.

The cost of a hot drink scald.

Approximately 6400 children per year are admitted to UK hospitals for treatment of burns [National Burn Care Review Committee Report (NBCRC). Standards and Strategy for Burn Care: a review of burn care in the British Isles. 2001.]. This paper investigates the financial costs involved in the management of uncomplicated, minor paediatric scalds. Three cases (2-4% TBSA scalds) were studied to quantify consumables used, services required during management and costs obtained from appropriate Purchasing Departments and Directorate Accountants. Management in all cases involved a general anaesthetic for cleaning of wounds, application of BioBrane (Bertek Pharmaceuticals) and dressings, observation on Children's Ward and discharge following wound review at 48 h. The calculated mean average cost per case was pound1850. In the period 01/12/2002-30/11/2003, 144 children were admitted to Frenchay hospital, Bristol, for treatment of a minor burn or scald (less than 10%TBSA). This caseload is therefore estimated to currently cost pound266,400 per year. These findings may facilitate improved planning for future resource allocation and could also contribute evidence towards the cost effectiveness of prevention strategies.

A qualitative evaluation of the immunization program in Papua New Guinea.

OBJECTIVE: An in-depth evaluation of rural immunization services in Papua New Guinea was conducted to determine the reasons for poor immunization coverage, as well as to document the impact of recent efforts to strengthen the national immunization program. METHOD: A qualitative process was used to complement quantitative monitoring data. An interview process, based on open-ended questions, active listening and observation, was designed whereby a team of program supervisors collected information from rural health staff. The teams interviewed health staff in 30 health centres that were selected to provide examples of contrasting field situations. RESULTS: This qualitative review provided valuable detail about why immunization services were failing, encompassing locally specific weaknesses, such as logistic reasons for not conducting outreach, and generic systemic problems such as lack of access to funding. In addition, the information gathered provided details on local solutions developed by better-performing facilities. Both these aspects added significant value to quantitative measures of program performance (derived from national health information system data and analysis of supervision checklists). The review also captured a number of behavioural reasons that will need to be overcome before an improvement in the services can be expected. CONCLUSIONS AND IMPLICATIONS: This in-depth evaluation provided valuable information about problems in peripheral immunization clinics and identified local solutions. The high level of detail collected will be important for planning future strengthening of the health system. The study modelled a supportive form of supervision with the potential to improve outcomes from future supervisory visits. Some of the major barriers to improved immunization were locally specific organizational issues, as well as complex human problems. While some issues can be remedied through further strengthening of immunization systems, others lack easy, rapid solutions.

Complications of inguinal herniotomy are comparable in term and premature infants.

PURPOSE: Inguinal hernias are common, and prevalence is highest in premature males. Recognised complications include recurrence, iatrogenic cryptorchidism and testicular atrophy. We reviewed complication rates following inguinal herniotomy (IH), comparing premature (gestation <36 weeks) and term infants. METHODS: A retrospective case note review of infants aged 0-12 months undergoing IH between January 2006 and December 2010. Data collected included demographics, side of hernia, incarceration, complications, duration of follow-up and need for further surgery. Comparison was made using unpaired student t test and Fishers exact test. RESULTS: Four hundred and eight patients underwent IH (365 male, 42 female, 1 complete androgen insensitivity); 197 were premature (prem), mean weight 3.81 kg (1.02-9.4); 211 were term (gestation ≥36 weeks), mean weight 5.85 kg (2.4-11.7), p = 0.0001 versus prem. Total herniotomies performed = 472 (131 Left, 213 Right, 64 bilateral); 89 hernias were incarcerated at presentation (60 prem vs. 29 term, p = 0.0001). Bowel resection was required in six patients (5 prem vs. 1 term, p = 0.1109), and 14 had simultaneous orchidopexy (12 prem vs. 2 term, p = 0.0049). Early post-operative complication rate 2.8 % (8 prem vs. 5 term; p = 0.4037). Two hundred and forty patients attended follow-up; 58.8 % (125 prem, 115 term). This group accounted for 279 IH (264 male, 15 female). Mean follow-up = 5 months (0.5-36). Complication rates: recurrence 2.7 %, metachronous hernia 7.5 %, iatrogenic cryptorchidism 3.8 % and testicular atrophy 0.7 %. CONCLUSION: No significant difference was found in complication rates between premature and term infants despite significantly more premature infants presenting with incarcerated hernias.

A Prospective, Placebo-Controlled Pilot Evaluation of the Effect of Omeprazole on Serum Calcium, Magnesium, Cobalamin, Gastrin Concentrations, and Bone in Cats.

BACKGROUND: Chronic proton pump inhibitor administration has been associated with electrolyte and cobalamin deficiency, disrupted bone homeostasis, hypergastrinemia, and rebound acid hypersecretion in humans. It is unknown if this occurs in cats. OBJECTIVES: Prolonged oral omeprazole results in altered bone mineral density or content, serum calcium, magnesium, cobalamin, and gastrin concentrations in healthy cats. ANIMALS: Six healthy adult DSH cats. METHODS: In a within subjects, before and after design, cats received placebo followed by omeprazole (0.83-1.6 mg/kg PO q12h) for 60 days each. Analysis of serum calcium, magnesium, cobalamin, and gastrin concentrations was performed on days 0, 30, and 60. Bone density and content were evaluated on days 0 and 60 of each intervention. Continuous data were analyzed using a two-way ANOVA (α = 0.006). On day 60 of omeprazole administration, continuous intragastric pH monitoring was performed in 2 cats to evaluate the effects of abrupt withdrawal of omeprazole. RESULTS: No significant changes were detected between treatments for any variables, except serum gastrin, which was significantly higher during omeprazole treatment in comparison to placebo (P = 0.002). Evidence of gastric hyperacidity was seen in both cats in which intragastric pH monitoring was performed following cessation of omeprazole. CONCLUSIONS AND CLINICAL IMPORTANCE: Although further studies with larger populations of cats will be needed to draw any definitive conclusions, these preliminary results suggest that prolonged PPI treatment results in hypergastrinemia and abrupt PPI withdrawal might result in RAH in cats.

Absence of evidence for increase in risk for autism or attention-deficit hyperactivity disorder following antidepressant exposure during pregnancy: a replication study.

Multiple studies have examined the risk of prenatal antidepressant exposure and risk for autism spectrum disorder (ASD) or attention-deficit hyperactivity disorder (ADHD), with inconsistent results. Precisely estimating such risk, if any, is of great importance in light of the need to balance such risk with the benefit of depression and anxiety treatment. We developed a method to integrate data from multiple New England health systems, matching offspring and maternal health data in electronic health records to characterize diagnoses and medication exposure. Children with ASD or ADHD were matched 1:3 with children without neurodevelopmental disorders. Association between maternal antidepressant exposure and ASD or ADHD liability was examined using logistic regression, adjusting for potential sociodemographic and psychiatric confounding variables. In new cohorts of 1245 ASD cases and 1701 ADHD cases, along with age-, sex- and socioeconomic status matched controls, neither disorder was significantly associated with prenatal antidepressant exposure in crude or adjusted models (adjusted odds ratio 0.90, 95% confidence interval 0.50-1.54 for ASD; 0.97, 95% confidence interval 0.53-1.69 for ADHD). Pre-pregnancy antidepressant exposure significantly increased risk for both disorders. These results suggest that prior reports of association between prenatal antidepressant exposure and neurodevelopmental disease are likely to represent a false-positive finding, which may arise in part through confounding by indication. They further demonstrate the potential to integrate data across electronic health records studies spanning multiple health systems to enable efficient pharmacovigilance investigation.

The epidemiology of measles: thirty years of vaccination.

Measles is a highly infectious disease which has a major impact on child survival, particularly in developing countries. The importance of understanding the epidemiology of this disease is underlined by its ability to change rapidly in the face of increasing immunization coverage. Much is still to be learned about measles epidemiology and the best strategies for administering measles vaccines, as well as about the biological mechanisms of action of measles vaccines. However, it is clear that tremendous progress can be made in preventing death and disease from measles with existing knowledge about the disease, and by using the presently available vaccines and applying well tried methods of treating cases. Research in the coming decade may provide improved strategies and more effective vaccines for use in immunization programmes.

Clinical confirmation of organophosphate poisoning by serial cholinesterase analyses.

Three groups of agricultural workers with a history of exposure to organophosphate pesticides were followed up to evaluate the utility of sequential postexposure cholinesterase analyses to confirm organophosphate intoxication in the absence of baseline cholinesterase values. Three or more cholinergic symptoms were reported by 50 of the 72 patients. Initial plasma and red blood cell cholinesterase values of 45 of the workers were above the lower limit of the laboratory normal range. Follow-up examinations, including cholinesterase analyses, were conducted on 57 patients. When final postexposure cholinesterase determinations were taken as estimates of individual normal baseline values, the plasma and red blood cell activity of the three groups was shown to have been inhibited. The data support the use of sequential postexposure plasma cholinesterase analyses to confirm the diagnosis of organophosphate-induced illness in the absence of baseline values.

Accuracy of home blood glucose monitors.

OBJECTIVE: To determine the accuracy of five home blood glucose monitors (HBGM) in reference to a standard laboratory reference method. RESEARCH DESIGN AND METHODS: The study took place in the laboratory of a 350-bed private acute-care hospital. Subjects were a sample of convenience of 207 diabetic and nondiabetic adult and pediatric patients scheduled for fasting blood work that included a blood glucose test. Venous blood samples were collected for laboratory determination of blood glucose level. A separate sample was collected for testing on two each of five HBGMs: AccuChek II M, Tracer II, ExacTech, Glucometer II with Memory, and One Touch. RESULTS: Multiple regression analysis showed that all 10 monitors could be used to predict laboratory blood glucose values. The monitors with the highest predictabilities were One Touch, Tracer II, and AccuChek II M. Consistency between monitors of the same brand was lowest with One Touch. AccuChek II M had the smallest SD between the 2 monitors used in the study. CONCLUSIONS: HBGM can be used to predict actual laboratory values of blood glucose. However, the controlled environment of the study should be considered and patient education made a high priority when recommending monitors.

Forensic psychiatry and applied clinical ethics: theory and practice.

The authors briefly describe and then apply a new method--applied clinical ethics--for identifying and working with ethical problems. This method, starting from the clinical context, develops ethical constructs that may be tested in clinical practice and revised if required. The work was done in the context of a combined university-county forensic psychiatric service. The authors discuss three of the identified ethical issues: effects of deinstitutionalization, countertransference with forensic populations, and prediction of dangerousness. They discuss the basis for developing ethical norms from clinical experience and suggest ethical guidelines for medical practice.

Family or individual therapy: the ethics of modality choice.

The authors examine the ethical issues in choosing between individual and social unit (marital and family) therapies. Although usually neglected in the literature, these ethical questions are important and complex. A general systems perspective is used to provide a framework for ethical analysis. The core of the ethical problem is shown to be the interdependence and irreducible conflict inherent between the individual and social unit levels. The authors outline a general systems approach to identification and consideration of these ethical issues in clinical practice.