Impacts of fire and prospects for recovery in a tropical peat forest ecosystem.

Uncontrolled fires place considerable burdens on forest ecosystems, compromising our ability to meet conservation and restoration goals. A poor understanding of the impacts of fire on ecosystems and their biodiversity exacerbates this challenge, particularly in tropical regions where few studies have applied consistent analytical techniques to examine a broad range of ecological impacts over multiyear time frames. We compiled 16 y of data on ecosystem properties (17 variables) and biodiversity (21 variables) from a tropical peatland in Indonesia to assess fire impacts and infer the potential for recovery. Burned forest experienced altered structural and microclimatic conditions, resulting in a proliferation of nonforest vegetation and erosion of forest ecosystem properties and biodiversity. Compared to unburned forest, habitat structure, tree density, and canopy cover deteriorated by 58 to 98%, while declines in species diversity and abundance were most pronounced for trees, damselflies, and butterflies, particularly for forest specialist species. Tracking ecosystem property and biodiversity datasets over time revealed most to be sensitive to recurrent high-intensity fires within the wider landscape. These megafires immediately compromised water quality and tree reproductive phenology, crashing commercially valuable fish populations within 3 mo and driving a gradual decline in threatened vertebrates over 9 mo. Burned forest remained structurally compromised long after a burn event, but vegetation showed some signs of recovery over a 12-y period. Our findings demonstrate that, if left uncontrolled, fire may be a pervasive threat to the ecological functioning of tropical forests, underscoring the importance of fire prevention and long-term restoration efforts, as exemplified in Indonesia.

Major changes in domain arrangements are associated with the evolution of termites.

Domains as functional protein units and their rearrangements along the phylogeny can shed light on the functional changes of proteomes associated with the evolution of complex traits like eusociality. This complex trait is associated with sterile soldiers and workers, and long-lived, highly fecund reproductives. Unlike in Hymenotpera (ants, bees, and wasps), the evolution of eusociality within Blattodea, where termites evolved from within cockroaches, was accompanied by a reduction in proteome size, raising the question of whether functional novelty was achieved with existing rather than novel proteins. To address this, we investigated the role of domain rearrangements during the evolution of termite eusociality. Analysing domain rearrangements in the proteomes of three solitary cockroaches and five eusocial termites, we inferred more than 5000 rearrangements over the phylogeny of Blattodea. The 90 novel domain arrangements that emerged at the origin of termites were enriched for several functions related to longevity, such as protein homeostasis, DNA repair, mitochondrial activity, and nutrient sensing. Many domain rearrangements were related to changes in developmental pathways, important for the emergence of novel castes. Along with the elaboration of social complexity, including permanently sterile workers and larger, foraging colonies, we found 110 further domain arrangements with functions related to protein glycosylation and ion transport. We found an enrichment of caste-biased expression and splicing within rearranged genes, highlighting their importance for the evolution of castes. Furthermore, we found increased levels of DNA methylation among rearranged compared to non-rearranged genes suggesting fundamental differences in their regulation. Our findings indicate an importance of domain rearrangements in the generation of functional novelty necessary for termite eusociality to evolve.

Intermittent cytomegalovirus infection alters neurobiological metabolism and induces cognitive deficits in mice.

Risk factors contributing to dementia are multifactorial. Accumulating evidence suggests a role for pathogens as risk factors, but data is largely correlative with few causal relationships. Here, we demonstrate that intermittent murine cytomegalovirus (MCMV) infection of mice, alters blood brain barrier (BBB) permeability and metabolic pathways. Increased basal mitochondrial function is observed in brain microvessels cells (BMV) exposed to intermittent MCMV infection and is accompanied by elevated levels of superoxide. Further, mice score lower in cognitive assays compared to age-matched controls who were never administered MCMV. Our data show that repeated systemic infection with MCMV, increases markers of neuroinflammation, alters mitochondrial function, increases markers of oxidative stress and impacts cognition. Together, this suggests that viral burden may be a risk factor for dementia. These observations provide possible mechanistic insights through which pathogens may contribute to the progression or exacerbation of dementia.

Reporting of determinants of health inequities and participant characteristics in randomized controlled trials of systemic lupus erythematosus in Canada: A scoping review.

OBJECTIVE: To report participant characteristics relevant to identifying health inequities in systemic lupus erythematosus (SLE) randomized controlled trials conducted in Canada. METHODS: We conducted a scoping review by searching MEDLINE (Ovid) and Embase (1990 to June 2023), and CENTRAL (inception to June 2023). Eligible studies: used an RCT design; evaluated interventions (pharmacologic and non-pharmacologic) among SLE patients aged ≥18 years; and were conducted in Canada. Data extraction was guided by the Campbell and Cochrane Equity Methods Group's PROGRESS-Plus framework on 11 factors leading to health inequities (Place of residence; Race, culture, ethnicity, and language; Occupation; Gender and sex; Religion; Education; Socioeconomic status; Social capital; Plus: Personal characteristics associated with discrimination; Features of relationships; and Time-dependent relationships). RESULTS: Of 1901 unique records, 6 met the inclusion criteria. Sex and age were the only PROGRESS factors that were reported in all studies. The majority of participants were female (84.4% to 100%), and mean ages of participants ranged from 42 to 52.3 years. Place of residence, race, education, and social capital were reported in three studies. Socioeconomic status was reported in two studies, and occupation was reported in one study. Religion, features of relationships, and time-dependent relationships were not reported in any included studies. CONCLUSION: Limited reporting of determinants of health inequities in RCTs for SLE in Canada suggests the need for reporting standards to support equity, diversity, and inclusion practices in research.

Can prediction models for hospital readmission be improved by incorporating patient-reported outcome measures? A systematic review and narrative synthesis.

PURPOSE: To investigate the roles, challenges, and implications of using patient-reported outcome measures (PROMs) in predicting the risk of hospital readmissions. METHODS: We systematically searched four bibliometric databases for peer-reviewed studies published in English between 1 January 2000 and 15 June 2023 and used validated PROMs to predict readmission risks for adult populations. Reported studies were analysed and narratively synthesised in accordance with the CHARMS and PRISMA guidelines. RESULTS: Of the 2858 abstracts reviewed, 23 studies met predefined eligibility criteria, representing diverse geographic regions and medical specialties. Among those, 19 identified the positive contributions of PROMs in predicting readmission risks. Seven studies utilised generic PROMs exclusively, eleven used generic and condition-specific PROMs, while 5 focussed solely on condition-specific PROMs. Logistic regression was the most used modelling approach, with 13 studies aiming at predicting 30-day all-cause readmission risks. The c-statistic, ranging from 0.54 to 0.84, was reported in 22/23 studies as a measure of model discrimination. Nine studies reported model calibration in addition to c-statistic. Thirteen studies detailed their approaches to dealing with missing data. CONCLUSION: Our study highlights the potential of PROMs to enhance predictive accuracy in readmission models, while acknowledging the diversity in data collection methods, readmission definitions, and model evaluation approaches. Recognizing that PROMs serve various purposes beyond readmission reduction, our study supports routine data collection and strategic integration of PROMs in healthcare practices to improve patient outcomes. To facilitate comparative analysis and broaden the use of PROMs in the prediction framework, it is imperative to consider the methodological aspects involved.

A scoping review of triage approaches for the referral of patients with suspected inflammatory arthritis, from primary to rheumatology care.

We aimed to (1) identify existing triage approaches for referral of patients with suspected inflammatory arthritis (IA) from primary care physicians (PCP) to rheumatologists, (2) describe their characteristics and methodologies for clinical use, and (3) report their level of validation for use in a publicly funded healthcare system. The comprehensive search strategy of multiple databases up to October 2023 identified relevant literature and focussed on approaches applied at the PCP-Rheumatologist referral stage. Primary, quantitative studies, reported in English were included. Triage approaches were grouped into patient conditions as defined by the authors of the reports, including IA, its subtypes and combinations. 13952 records were identified, 425 full text reviewed and 55 reports of 53 unique studies were included. Heterogeneity in disease nomenclature and study sample pretest probability was found. The number of published studies rapidly increased after 2012. Studies were mostly from Europe and North America, in IA and Axial Spondyloarthritis (AxSpa). We found tools ranging the continuum of development with those best performing, indicated by the area under the receiver operating curve (AUC) >0.8), requiring only patient-reported questions. There were AUCs for some tools reported from multiple studies, these were in the outstanding to excellent range for the Early IA Questionnaire (EIAQ) (0.88 to 0.92), acceptable for the Case Finding AxSpa (CaFaSpa) (0.70 to 0.75), and poor to outstanding for the Psoriasis Epidemiology Screening Tool (PEST) (0.61 to 0.91). Given the clinical urgency to improve rheumatology referrals and considering the good.

A combinatorial DNA assembly approach to biosynthesis of N-linked glycans in E. coli.

Glycoengineering of recombinant glycans and glycoconjugates is a rapidly evolving field. However, the production and exploitation of glycans has lagged behind that of proteins and nucleic acids. Biosynthetic glycoconjugate production requires the coordinated cooperation of three key components within a bacterial cell: a substrate protein, a coupling oligosaccharyltransferase, and a glycan biosynthesis locus. While the acceptor protein and oligosaccharyltransferase are the products of single genes, the glycan is a product of a multigene metabolic pathway. Typically, the glycan biosynthesis locus is cloned and transferred en bloc from the native organism to a suitable Escherichia coli strain. However, gene expression within these pathways has been optimized by natural selection in the native host and is unlikely to be optimal for heterologous production in an unrelated organism. In recent years, synthetic biology has addressed the challenges in heterologous expression of multigene systems by deconstructing these pathways and rebuilding them from the bottom up. The use of DNA assembly methods allows the convenient assembly of such pathways by combining defined parts with the requisite coding sequences in a single step. In this study, we apply combinatorial assembly to the heterologous biosynthesis of the Campylobacter jejuni  N-glycosylation (pgl) pathway in E. coli. We engineered reconstructed biosynthesis clusters that faithfully reproduced the C. jejuni heptasaccharide glycan. Furthermore, following a single round of combinatorial assembly and screening, we identified pathway clones that outperform glycan and glycoconjugate production of the native unmodified pgl cluster. This platform offers a flexible method for optimal engineering of glycan structures in E. coli.

More effective transposon regulation in fertile, long-lived termite queens than in sterile workers.

Transposable elements (TEs) are mobile genetic sequences, which can cause the accumulation of genomic damage in the lifetime of an organism. The regulation of TEs, for instance via the piRNA-pathway, is an important mechanism to protect the integrity of genomes, especially in the germ-line where mutations can be transmitted to offspring. In eusocial insects, soma and germ-line are divided among worker and reproductive castes, so one may expect caste-specific differences in TE regulation to exist. To test this, we compared whole-genome levels of repeat element transcription in the fat body of female workers, kings and five different queen stages of the higher termite, Macrotermes natalensis. In this species, queens can live over 20 years, maintaining near maximum reproductive output, while sterile workers only live weeks. We found a strong, positive correlation between TE expression and the expression of neighbouring genes in all castes. However, we found substantially higher TE activity in workers than in reproductives. Furthermore, TE expression did not increase with age in queens, despite a sevenfold increase in overall gene expression, due to a significant upregulation of the piRNA-pathway in 20-year-old queens. Our results suggest a caste- and age-specific regulation of the piRNA-pathway has evolved in higher termites that is analogous to germ-line-specific activity in solitary organisms. In the fat body of these termite queens, an important metabolic tissue for maintaining their extreme longevity and reproductive output, an efficient regulation of TEs likely protects genome integrity, thus further promoting reproductive fitness even at high age.

Exploring Models for an International Legal Agreement on the Global Antimicrobial Commons: Lessons from Climate Agreements.

An international legal agreement governing the global antimicrobial commons would represent the strongest commitment mechanism for achieving collective action on antimicrobial resistance (AMR). Since AMR has important similarities to climate change-both are common pool resource challenges that require massive, long-term political commitments-the first article in this special issue draws lessons from various climate agreements that could be applicable for developing a grand bargain on AMR. We consider the similarities and differences between the Paris Climate Agreement and current governance structures for AMR, and identify the merits and challenges associated with different international forums for developing a long-term international agreement on AMR. To be effective, fair, and feasible, an enduring legal agreement on AMR will require a combination of universal, differentiated, and individualized requirements, nationally determined contributions that are regularly reviewed and ratcheted up in level of ambition, a regular independent scientific stocktake to support evidence informed policymaking, and a concrete global goal to rally support.

Governing the Global Antimicrobial Commons: Introduction to Special Issue.

Antimicrobial resistance is one of the greatest public health crises of our time. The natural biological process that causes microbes to become resistant to antimicrobial drugs presents a complex social challenge requiring more effective and sustainable management of the global antimicrobial commons-the common pool of effective antimicrobials. This special issue of Health Care Analysis explores the potential of two legal approaches-one long-term and one short-term-for managing the antimicrobial commons. The first article explores the lessons for antimicrobial resistance that can be learned from recent climate change agreements, and the second article explores how existing international laws can be adapted to better support global action in the short-term.

Making Use of Existing International Legal Mechanisms to Manage the Global Antimicrobial Commons: Identifying Legal Hooks and Institutional Mandates.

Antimicrobial resistance (AMR) is an urgent threat to global public health and development. Mitigating this threat requires substantial short-term action on key AMR priorities. While international legal agreements are the strongest mechanism for ensuring collaboration among countries, negotiating new international agreements can be a slow process. In the second article in this special issue, we consider whether harnessing existing international legal agreements offers an opportunity to increase collective action on AMR goals in the short-term. We highlight ten AMR priorities and several strategies for achieving these goals using existing "legal hooks" that draw on elements of international environmental, trade and health laws governing related matters that could be used as they exist or revised to include AMR. We also consider the institutional mandates of international authorities to highlight areas where additional steps could be taken on AMR without constitutional changes. Overall, we identify 37 possible mechanisms to strengthen AMR governance using the International Health Regulations, the Agreement on the Application of Sanitary and Phytosanitary Measures, the Agreement on Trade-Related Aspects of Intellectual Property Rights, the Agreement on Technical Barriers to Trade, the International Convention on the Harmonized Commodity Description and Coding System, and the Basel, Rotterdam, and Stockholm conventions. Although we identify many shorter-term opportunities for addressing AMR using existing legal hooks, none of these options are capable of comprehensively addressing all global governance challenges related to AMR, such that they should be pursued simultaneously with longer-term approaches including a dedicated international legal agreement on AMR.

Benefit-harm analysis of azithromycin for the prevention of acute exacerbations of chronic obstructive pulmonary disease.

BACKGROUND: Low-dose oral azithromycin therapy is recommended as a preventive treatment for acute exacerbations of COPD. However, the overall benefit-harm balance of this treatment has not been well studied. METHODS: A probabilistic Markov model of COPD was created to simulate the course of COPD over 20 years. The model was populated with evidence from the literature and dedicated data analysis. The benefit of azithromycin was modelled as a reduction in exacerbation rates. Adverse events, including cardiovascular events, hearing loss, gastrointestinal symptoms and antimicrobial resistance (leading to a gradual decline in the effectiveness of azithromycin), were considered. All outcomes were assigned a health-related utility weight to estimate the overall net change in the quality-adjusted life year (QALY) associated with the use of azithromycin. RESULTS: In patients with a positive exacerbation history, azithromycin resulted in a net QALY gain of 17.9 per 100 patients (99.8% probability of expected QALY gain) over 20 years. The net benefit increased to 21.8 QALYs per 100 patients (99.9% probability of expected QALY gain) among the 'frequent exacerbator' subgroup. Azithromycin was not net beneficial among those without any moderate/severe exacerbations in the previous year. Findings were robust against series of sensitivity, scenario and threshold analyses. CONCLUSIONS: Long-term therapy with azithromycin confers a net benefit to ex-smoker patients with COPD with a recent history of exacerbations and an even larger benefit to those who are frequent exacerbators.

Clinician preferences for neurotechnologies in pediatric drug-resistant epilepsy: A discrete choice experiment.

OBJECTIVE: Novel and minimally invasive neurotechnologies offer the potential to reduce the burden of epilepsy while avoiding the risks of conventional resective surgery. Few neurotechnologies have been tested in randomized controlled trials with pediatric populations, leaving clinicians to face decisions about whether to recommend these treatments with insufficient evidence about the relevant risks and benefits. This study specifically explores the preferences of clinicians for treating pediatric drug-resistant epilepsy (DRE) with novel neurotechnologies. METHODS: A discrete-choice experiment (DCE) was designed to elicit the preferences of clinicians with experience in treating children with DRE using novel neurotechnological interventions. The preferences for six key attributes used when making treatment decisions (chances of clinically significant improvement in seizures, major and minor risks from intervention, availability of evidence, financial burden for the family, and access to the intervention) were estimated using a conditional logit model. The estimates from this model were then used to predict the adoption of existing novel neurotechnological interventions. RESULTS: Sixty-eight clinicians completed the survey: 33 neurosurgeons, 28 neurologists, and 7 other clinicians. Most clinicians were working in the United States (74%), and the remainder (26%) in Canada. All attributes, apart from the nearest location with access to the intervention, influenced preferences significantly. The chance of clinically significant improvement in seizures was the most positive influence on clinician preferences, but low-quality evidence and a higher risk of major complications could offset these preferences. Of the existing neurotechnological interventions, vagus nerve stimulation was predicted to have the highest likelihood of adoption; deep brain stimulation had the lowest likelihood of adoption. SIGNIFICANCE: The preferences of clinicians are drive primarily by the likelihood of achieving seizure freedom for their patients, but preferences for an intervention are largely eradicated if only low quality of evidence supporting the intervention is available. Until better evidence supporting the use of potentially effective, novel neurotechnologies becomes available, clinicians are likely to prefer more established treatments.

Development of simple, scalable protease production from Botrytis cinerea.

Heat haze-forming proteins are stable during winemaking and are typically removed via adsorption to bentonite. Proteolytic degradation is an alternative method to prevent wine-haze and offers the opportunity to reduce the environmental impacts and labor cost of the process. Herein, we describe the development of a production system for Botrytis cinerea proteases for the enzymatic degradation of heat haze-forming proteins. The effect of culture medium on the secretion of glucan by B. cinerea was investigated and methods to inactivate B. cinerea laccase in liquid culture medium were assessed. Protease production by B. cinerea was scaled up from 50 mL in shake flasks to 1 L in bioreactors, resulting in an increase in protease yield from 0.30 to 3.04 g L-1. Glucan secretion by B. cinerea was minimal in culture medium containing lactose as a carbon source and either lactic or sulfuric acid for pH control. B. cinerea laccases were inactivated by reducing the pH of culture supernatant to 1.5 for 1 h. B. cinerea proteases were concentrated and partially purified using ammonium sulfate precipitation. SWATH-MS identified aspartic acid protease BcAP8 amongst the precipitated proteins. These results demonstrate a simple, affordable, and scalable process to produce proteases from B. cinerea as a replacement for bentonite in winemaking. KEY POINTS: • Isolates of B. cinerea that produce proteases with potential for reducing wine heat-haze forming proteins were identified. • Media and fermentation optimization increased protease yield tenfold and reduced glucan secretion. • Low pH treatment inactivated laccases but not proteases.

Patient perspectives on the British Columbia Biosimilars Initiative: a qualitative descriptive study.

In May 2019, the Government of British Columbia (BC) announced the implementation of the Biosimilars Initiative, mandating the switch of biologic (originator) drugs to biosimilars for certain patient populations in the hopes of optimizing public resources. Through this qualitative study, we aimed to identify patients' perspectives as they undergo this change. From October 2019 to July 2020, we conducted nine pre- and six post-switch to biosimilar interviews with BC, English speaking participants, who were 18 years or older, and were currently taking a biologic medication. Participants were interviewed pre- and post-switch to a biosimilar medication and interviews were audio-recorded and transcribed verbatim for qualitative analysis. Interviews were thematically analysed and major themes and sub-categories were elucidated. The themes derived from pre and post-switch interviews captured participants' anticipated or experienced barriers and enablers to the policy change. In general, the fears and apprehension of participants approaching the switch, including concerns surrounding the efficacy and safety of biosimilars, were addressed by their rheumatologist and social support circles. For the most part, participants were able to successfully manage their disease regardless of their baseline concerns about efficacy and safety. Experiences of changes in health delivery models were also observed secondary to the impact of the COVID-19 pandemic amongst participants. This study is the first of its kind to characterize the patient perspective regarding the BC Biosimilars Initiative. The incorporation of the patient perspective, including adequate provider-patient communication and shared decision-making can help to inform future non-medical switching policy changes.

The impact of introducing multidisciplinary care assessments on access to rheumatology care in British Columbia: an interrupted time series analysis.

BACKGROUND: In 2011 the British Columbia (BC) Ministry of Health introduced a new fee-for-service billing code that allowed "Multidisciplinary Care Assessment" (MCA). This change has the potential to change access to and quality of care for patients. This study aimed to explore the impact on access to rheumatology services in the province. METHODS: Fee-for-service rheumatology billings were evaluated for each rheumatologist 2 years before and after use of the MCA code. Numbers of 1) unique patients and 2) services provided per month were used as proxy measures of access to care. A multiple-baseline interrupted time series model assessed the impact of the MCA on levels and trends of the access outcomes. RESULTS: Our analysis consisted of 82,360 patients cared for by 26 rheumatologists who billed for an MCA. In our primary analysis we observed a sustained increase in the mean number of unique patients of 4.9% (95% CI: 0.0% to 9.9%, p = 0.049) and the mean number of services of 7.1% (95% CI: 1.0% to 13.6%, (p = 0.021), per month provided by a rheumatologist, corresponding to the initial use of MCA. CONCLUSION: The introduction of the MCA code was associated with an initial increase in the measures of access, which was maintained but did not increase over time. Our study suggests that the use of Multidisciplinary Care Assessment can contribute to expanding and/or sustaining access to care for people with complex chronic conditions, like rheumatic diseases.

'Cortical Hand' in the Emergency Department: Two Case Reports.

BACKGROUND: Cortical hand strokes affect the 'hand knob' of the motor cortex, resulting in isolated distal upper limb or hand weakness. They are rare and can be easily misdiagnosed for peripheral lesions. CASE REPORTS: Case 1: A 59-year-old man presented to the Emergency Department (ED) after noticing left hand weakness while driving. There was no sensory deficit noted. A full neurological examination suggested an upper motor neurone rather than a peripheral nerve lesion. This was confirmed by a magnetic resonance imaging scan of his brain. Case 2: An 88-year-old man presented to the ED after developing sudden-onset left hand weakness while completing a newspaper puzzle. Power returned gradually over approximately 4 h, with no sensory symptoms being noted. A transient ischemic attack leading to cortical hand was diagnosed. WHY SHOULD AN EMERGENCY PHYSICIAN BE AWARE OF THIS?: Cortical hand strokes are a rare, but important, differential for wrist drop. They are often first strokes and embolic in nature. Therefore, correct diagnosis is vital to enable initiation of secondary prevention.

Probabilistic seasonal dengue forecasting in Vietnam: A modelling study using superensembles.

BACKGROUND: With enough advanced notice, dengue outbreaks can be mitigated. As a climate-sensitive disease, environmental conditions and past patterns of dengue can be used to make predictions about future outbreak risk. These predictions improve public health planning and decision-making to ultimately reduce the burden of disease. Past approaches to dengue forecasting have used seasonal climate forecasts, but the predictive ability of a system using different lead times in a year-round prediction system has been seldom explored. Moreover, the transition from theoretical to operational systems integrated with disease control activities is rare. METHODS AND FINDINGS: We introduce an operational seasonal dengue forecasting system for Vietnam where Earth observations, seasonal climate forecasts, and lagged dengue cases are used to drive a superensemble of probabilistic dengue models to predict dengue risk up to 6 months ahead. Bayesian spatiotemporal models were fit to 19 years (2002-2020) of dengue data at the province level across Vietnam. A superensemble of these models then makes probabilistic predictions of dengue incidence at various future time points aligned with key Vietnamese decision and planning deadlines. We demonstrate that the superensemble generates more accurate predictions of dengue incidence than the individual models it incorporates across a suite of time horizons and transmission settings. Using historical data, the superensemble made slightly more accurate predictions (continuous rank probability score [CRPS] = 66.8, 95% CI 60.6-148.0) than a baseline model which forecasts the same incidence rate every month (CRPS = 79.4, 95% CI 78.5-80.5) at lead times of 1 to 3 months, albeit with larger uncertainty. The outbreak detection capability of the superensemble was considerably larger (69%) than that of the baseline model (54.5%). Predictions were most accurate in southern Vietnam, an area that experiences semi-regular seasonal dengue transmission. The system also demonstrated added value across multiple areas compared to previous practice of not using a forecast. We use the system to make a prospective prediction for dengue incidence in Vietnam for the period May to October 2020. Prospective predictions made with the superensemble were slightly more accurate (CRPS = 110, 95% CI 102-575) than those made with the baseline model (CRPS = 125, 95% CI 120-168) but had larger uncertainty. Finally, we propose a framework for the evaluation of probabilistic predictions. Despite the demonstrated value of our forecasting system, the approach is limited by the consistency of the dengue case data, as well as the lack of publicly available, continuous, and long-term data sets on mosquito control efforts and serotype-specific case data. CONCLUSIONS: This study shows that by combining detailed Earth observation data, seasonal climate forecasts, and state-of-the-art models, dengue outbreaks can be predicted across a broad range of settings, with enough lead time to meaningfully inform dengue control. While our system omits some important variables not currently available at a subnational scale, the majority of past outbreaks could be predicted up to 3 months ahead. Over the next 2 years, the system will be prospectively evaluated and, if successful, potentially extended to other areas and other climate-sensitive disease systems.

Evidence for reduced immune gene diversity and activity during the evolution of termites.

The evolution of biological complexity is associated with the emergence of bespoke immune systems that maintain and protect organism integrity. Unlike the well-studied immune systems of cells and individuals, little is known about the origins of immunity during the transition to eusociality, a major evolutionary transition comparable to the evolution of multicellular organisms from single-celled ancestors. We aimed to tackle this by characterizing the immune gene repertoire of 18 cockroach and termite species, spanning the spectrum of solitary, subsocial and eusocial lifestyles. We find that key transitions in termite sociality are correlated with immune gene family contractions. In cross-species comparisons of immune gene expression, we find evidence for a caste-specific social defence system in termites, which appears to operate at the expense of individual immune protection. Our study indicates that a major transition in organismal complexity may have entailed a fundamental reshaping of the immune system optimized for group over individual defence.

High prevalence of coinfection of azithromycin-resistant Mycoplasma genitalium with other STIs: a prospective observational study of London-based symptomatic and STI-contact clinic attendees.

OBJECTIVES: Azithromycin treatment of Chlamydia trachomatis (CT) may not be adequate to treat concomitant Mycoplasma genitalium (MG) infection, and particularly if MG has macrolide resistance-associated mutations (MG-MRAMs). We estimated prevalence of coinfections of CT with MG carrying MRAM, and risk factors for MG-MRAM among a sexual health clinic population. STUDY DESIGN AND SETTING: Among symptomatic and STI-contact clinic attendees in London, prevalence of CT-MG coinfection and MG-MRAM were estimated using nucleic acid amplification testing and Sanger sequencing, respectively, and their associated risk factors analysed using logistic regression. RESULTS: MG prevalence was 7.5% (23/307), 17.3% (30/173), and 11.4% (8/70) in females, men who have sex with women (MSW) and men who have sex with men (MSM), respectively; MG coinfection in CT-infected participants represented 28.0% (7/25), 13.5% (5/37), 0.0% (0/0), respectively. Presence of MG-MRAM was 39.1% (9/23) in female swabs, 70.0% (21/30) in MSW urine and 83.3% (5/6) in MSM rectal swabs. In multivariate analyses, coinfection with another STI was strongly associated with MG-MRAM (OR: 7.19; 95% CI: 2.4 to 21.5). CONCLUSION: A significant proportion of participants in our study of symptomatic patients and STI contacts were infected with macrolide-resistant MG, suggesting that testing for MG and MRAM, for MG positives, might be clinically useful. The findings also suggest services explore potential benefits of testing CT positive samples for MG in these patient groups. Where MG testing is not available, potential high rates of MG coinfection should be borne in mind when considering azithromycin in the treatment of CT among STI contacts and symptomatic patients.