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Abstract Background Reducing Emissions from Deforestation and forest Degradation (REDD+) is a program established under the United Nations Framework Convention on Climate Change (UNFCCC) to reduce carbon emissions from forests in developing countries. REDD+ uses an incentive-based approach whereby participating countries are paid to reduce forest carbon loss and increase carbon storage. Country-level carbon accounting is challenging, and estimates of uncertainty in emission reductions are increasingly required in REDD+ reports. This requirement is hard to meet if countries lack the necessary resources, tools, and capabilities. Some REDD+ programs adjust their payments for the uncertainty reported, which presents a perverse incentive because uncertainties are larger if more sources of uncertainty are reported. We surveyed people involved in REDD+ reporting to assess current capacities and barriers to improving estimates of uncertainty. Results Representatives from 27 countries (44% of REDD+ countries at the time of survey implementation) responded to the survey. Nearly all respondents thought it important to include uncertainty in REDD+ reports, but most felt that the uncertainty reporting by their countries was inadequate. Our independent assessment of reports by these countries to the UNFCCC supported this opinion: Most countries reported uncertainty in activity data (91%) but not in emission factors (4–14%). Few countries use more advanced approaches to estimate uncertainty, such as Monte Carlo and Bayesian techniques, and many respondents indicated that they lack expertise, knowledge, or technical assistance. Other barriers include lack of financial resources and appropriate data. Despite these limitations, nearly all respondents indicated a strong desire to improve estimates of uncertainty in REDD+ reports. Conclusions The survey indicated that people involved in REDD+ reporting think it highly important to improve estimates of uncertainty in forest carbon accounting. To meet this challenge, it is essential to understand the obstacles countries face in quantifying uncertainty so we can identify where best to allocate efforts and funds. Investments in training and resources are clearly needed to better quantify uncertainty and would likely have successful outcomes given the strong desire for improvement. Tracking the efficacy of programs implemented to improve estimates of uncertainty would be useful for making further refinements.

Abstract Background Currently, there are more than two million people in prisons or jails, with nearly two-thirds meeting the criteria for a substance use disorder. Following these patterns, overdose is the leading cause of death following release from prison and the third leading cause of death during periods of incarceration in jails. Traditional quantitative methods analyzing the factors associated with overdose following incarceration may fail to capture structural and environmental factors present in specific communities. People with lived experiences in the criminal legal system and with substance use disorder hold unique perspectives and must be involved in the research process. Objective To identify perceived factors that impact overdose following release from incarceration among people with direct criminal legal involvement and experience with substance use. Methods Within a community-engaged approach to research, we used concept mapping to center the perspectives of people with personal experience with the carceral system. The following prompt guided our study: “What do you think are some of the main things that make people who have been in jail or prison more and less likely to overdose?” Individuals participated in three rounds of focus groups, which included brainstorming, sorting and rating, and community interpretation. We used the Concept Systems Inc. platform groupwisdom for our analyses and constructed cluster maps. Results Eight individuals (ages 33 to 53) from four states participated. The brainstorming process resulted in 83 unique factors that impact overdose. The concept mapping process resulted in five clusters: (1) Community-Based Prevention, (2) Drug Use and Incarceration, (3) Resources for Treatment for Substance Use, (4) Carceral Factors, and (5) Stigma and Structural Barriers. Conclusions Our study provides critical insight into community-identified factors associated with overdose following incarceration. These factors should be accounted for during resource planning and decision-making.

# Background Shoulder instabilities constitute a large proportion of shoulder injuries and have a wide range of presentations. While evidence regarding glenohumeral dislocations and associated risk factors has been reported, less is known regarding the full spectrum of instabilities and their risk factors. # Purpose The purpose of this systematic review was to identify modifiable risk factors to guide patient management decisions with regards to implementation of interventions to prevent or reduce the risk of shoulder instability. # Study Design Systematic Review # Methods A systematic, computerized search of electronic databases (CINAHL, Cochrane, Embase, PubMed, SportDiscus, and Web of Science) was performed. Inclusion criteria were: (1) a diagnosis of shoulder instability (2) the statistical association of at least one risk factor was reported, (3) study designs appropriate for risk factors, (4) written in English, and (5) used an acceptable reference standard for diagnosed shoulder instability. Titles and abstracts were independently screened by at least two reviewers. All reviewers examined the quality studies using the Newcastle-Ottawa Scale (NOS). At least two reviewers independently extracted information and data regarding author, year, study population, study design, criterion standard, and strength of association statistics with risk factors. # Results Male sex, participation in sport, hypermobility in males, and glenoid index demonstrated moderate to large risk associated with first time shoulder instability. Male sex, age \

Macroalgae have many potential applications and can make important contributions to sustainability and circular economy objectives. Macroalgae are degradable high-moisture biomaterials and drying is a necessary step, but drying is an energy and capital-intensive part of their production process. This study presents convective drying curves for commercially promising fresh and saltwater species (U. ohnoi and O. intermedium), obtained over a range of industry-relevant drying gas velocities (0.3–2 m/s) and material bulk densities (33–100 kg/m3). Pragmatic diffusion-based drying models that account for the influence of drying gas velocity, material bulk density, and material shrinkage are presented. Results provide critical insights into the validity of diffusion model assumptions for compressible biomaterials and new mechanisms describing gas penetration into such materials are proposed. The drying models provided in this work demonstrate a high degree of accuracy for both species.

Background The COVID-19 pandemic required science to provide answers rapidly to combat the outbreak. Hence, the reproducibility and quality of conducting research may have been threatened, particularly regarding privacy and data protection, in varying ways around the globe. The objective was to investigate aspects of reporting informed consent and data handling as proxies for study quality conduct.Methods A systematic scoping review was performed by searching PubMed and Embase. The search was performed on November 8th, 2020. Studies with hospitalised patients diagnosed with COVID-19 over 18 years old were eligible for inclusion. With a focus on informed consent, data were extracted on the study design, prestudy protocol registration, ethical approval, data anonymisation, data sharing and data transfer as proxies for study quality. For reasons of comparison, data regarding country income level, study location and journal impact factor were also collected.Results 972 studies were included. 21.3% of studies reported informed consent, 42.6% reported waivers of consent, 31.4% did not report consent information and 4.7% mentioned other types of consent. Informed consent reporting was highest in clinical trials (94.6%) and lowest in retrospective cohort studies (15.0%). The reporting of consent versus no consent did not differ significantly by journal impact factor (p=0.159). 16.8% of studies reported a prestudy protocol registration or design. Ethical approval was described in 90.9% of studies. Information on anonymisation was provided in 17.0% of studies. In 257 multicentre studies, 1.2% reported on data sharing agreements, and none reported on Findable, Accessible, Interoperable and Reusable data principles. 1.2% reported on open data. Consent was most often reported in the Middle East (42.4%) and least often in North America (4.7%). Only one report originated from a low-income country.Discussion Informed consent and aspects of data handling and sharing were under-reported in publications concerning COVID-19 and differed between countries, which strains study quality conduct when in dire need of answers.

Summary: Most existing studies characterizing severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)-specific T cell responses are peptide based. This does not allow evaluation of whether tested peptides are processed and presented canonically. In this study, we use recombinant vaccinia virus (rVACV)-mediated expression of SARS-CoV-2 spike protein and SARS-CoV-2 infection of angiotensin-converting enzyme (ACE)-2-transduced B cell lines to evaluate overall T cell responses in a small cohort of recovered COVID-19 patients and uninfected donors vaccinated with ChAdOx1 nCoV-19. We show that rVACV expression of SARS-CoV-2 antigen can be used as an alternative to SARS-CoV-2 infection to evaluate T cell responses to naturally processed spike antigens. In addition, the rVACV system can be used to evaluate the cross-reactivity of memory T cells to variants of concern (VOCs) and to identify epitope escape mutants. Finally, our data show that both natural infection and vaccination could induce multi-functional T cell responses with overall T cell responses remaining despite the identification of escape mutations.

ObjectivesCohort studies must implement effective retention strategies to produce internally valid and generalizable results. Ensuring all study participants are retained, particularly those involved in the criminal legal system, ensures study findings and future interventions will be relevant to this group, who are often lost to follow-up: critical to achieving health equity. Our objective was to characterize retention strategies and describe overall retention among an 18-month longitudinal cohort study of persons on community supervision prior to and during the COVID-19 pandemic.MethodsWe implemented various retention strategy best-practices (e.g., multiple forms of locator information, training study staff on rapport building, study-branded items). During the COVID-19 pandemic, we developed and describe new retention strategies. We calculated overall retention and analyzed differences between those retained and lost to follow-up by demographic characteristics.ResultsPrior to the start of the COVID-19 pandemic, 227 participants enrolled across three sites (N = 46 North Carolina; N = 99 Kentucky; N = 82 Florida). Of these, 180 completed the final 18-month visit, 15 were lost to follow-up, and 32 were ineligible. This resulted in an overall retention of 92.3% (180/195). While most participant characteristics did not differ by retention status, a greater proportion of those experiencing unstable housing were lost to follow-up.ConclusionOur findings highlight that when retention strategies are flexible, particularly during a pandemic, high retention is still achievable. In addition to retention best-practices (e.g., frequent requests for updated locator information) we suggest other studies consider retention strategies beyond the study participant (e.g., paying participant contacts) and incentivize on-time study visit completion (e.g., providing a bonus when completed the study visit on time).

Energy consumption is often a primary contributor to the cost of operation in aquaculture. Even on a moderately sized farm, excessive energy consumption can be a limiting factor in the success of an aquaculture business. Reducing operational costs can increase total profitability. Identifying inefficient energy use and implementing energy-efficient technologies can help reduce the total cost of operation. This publication is one in a series that details techniques and methods for reducing energy consumption to decrease operational costs on aquaculture facilities. In many aquaculture practices, especially finfish culture, water must be moved from one location to another. Pumping water often accounts for a significant portion of a facility’s energy use and operational costs. This publication discusses how variable frequency drives can be used to reduce energy consumption of pumps.

Eastern black rails (Laterallus jamaicensis jamaicensis) are among the rarest and least-studied birds in North America and were recently listed as threatened under the U.S. Endangered Species Act. Spatial models that predict habitat quality across the subspecies range are therefore needed to inform conservation, recovery, and monitoring efforts for this rare bird. We used data from 47,585 call-broadcast surveys collected at 7906 sites over a 3-decade period (1990s, 2000s, 2010s; 23 total years) to build species distribution models for eastern black rails. We used hierarchical Bayesian occupancy models and predictive model selection to develop multi-scale models that optimally predict habitat suitability for eastern black rails within tidal wetlands while also accounting for imperfect detection of these cryptic birds during field surveys. We also used raster regression techniques to translate model predictions into 30-m resolution maps of habitat suitability for eastern black rails within tidal wetlands along the eastern seaboard of the United States. The model predicted suitability of breeding habitat as a function of wetland attributes (e.g., cover of high marsh and terrestrial border), hydrologic modification, and disturbance from human development measured over multiple spatial scales. We also found differences in habitat relationships for eastern black rails when compared to models that included both North American subspecies of black rail. Important results included negative effects of shrub-scrub wetlands, and strong positive effects of high marsh, terrestrial border, and impoundments on breeding season occupancy. Our study provides an example of integrating detection-non-detection data and modern statistical methods to build predictive distribution models for an extremely rare species, while also providing rigorous predictions of breeding habitat quality for the eastern black rail within tidal wetlands. These models will facilitate optimal monitoring, habitat conservation, and recovery planning efforts for eastern black rails and provide a foundation for future research and conservation of this imperiled bird.

Management of ammonia, the primary waste product of fish, is critical to fish health, especially in intensive systems. At low concentrations, ammonia causes stress and damages gills and other tissues. Fish exposed to low levels of ammonia over time are more susceptible to bacterial infections, have poor growth, and do not tolerate routine handling well. At higher concentrations, it will kill fish. Many unexplained production losses have likely been caused by ammonia.

The energy consumption on aquaculture facilities can account for a large portion of on-farm operational costs. Energy associated with keeping aquatic plants and animals alive contributes to the total cost of operation. Even on a moderately sized farm, excessive energy consumption can be a limiting factor in the success of an aquaculture business. When recirculating aquaculture systems and indoor climate-controlled production methods are used, the cost of energy can be as large as the costs associated with labor and feed. Evaluating energy use on a facility allows for the opportunity to identify areas where energy may be used more efficiently. Increasing energy efficiency can help reduce overall operational costs and increase profitability. This publication is one in a series that details techniques and methods for reducing energy consumption on aquaculture farms. Prior to utilizing any energy saving opportunities, it is essential to understand how energy is used on a facility. This helps determine where changes in energy management and equipment can be most beneficial. This article discusses methods used to help estimate and understand current energy use. Subsequent publications will address specific areas where changes have proven to lower costs and improve efficiency on aquaculture facilities.

Abstract Introduction Mixed treatment comparisons (MTCs) are increasingly important in the assessment of the benefit–risk profile of pharmaceutical treatments for relapsing–remitting multiple sclerosis (RRMS). Interpretation of MTCs requires a clear understanding of the methods of analysis and population studied. The objectives of this work were to compare MTCs of pharmaceutical treatments for RRMS, including a detailed description of differences in populations, treatments assessed, methods used and findings; and to discuss key considerations when conducting an MTC. Methods Fourteen databases were searched until July 2019 to identify MTCs (published during or after 2010) in adults (at least 18 years of age) with RRMS or rapidly evolving severe RRMS treated with any form of pharmaceutical treatment. No language restriction was imposed. Results Twenty-seven MTCs assessing 21 treatments were identified. Comparison highlighted many differences in conduct and reporting between MTCs relating to the patient populations or treatments included, duration of follow-up and outcomes of interest measured. The lack of similarity between the MTCs leads to questions about variability in the robustness of analyses and makes comparisons between studies challenging. Conclusion Given the importance of MTCs for healthcare decision-making, it is imperative that reporting of methods, results and assumptions is clear and transparent to allow accurate interpretation of findings. For MTCs to be relevant, the choice of outcome measures should reflect clinical practice. Combination of treatments or of outcomes measured at different points of time should be avoided, as should imputation without justification. Furthermore, all approved treatment options should be included and updates of MTCs should be conducted when data for new treatments are published.

Abstract Background Since 2010, 27 mixed-treatment comparisons (MTCs) of disease-modifying therapies (DMTs) for multiple sclerosis have been published. However, there has been continued evolution in the field of MTCs. Additionally, limitations in methodological approach and reporting transparency, even in the most recent publications, makes interpretation and comparison of existing studies difficult. Objectives The objectives of this study are twofold: (1) to estimate the efficacy and safety of DMTs at European Commission-approved doses compared with placebo in adults with relapsing–remitting multiple sclerosis (RRMS) using MTC, and (2) to identify and address methodological challenges when performing MTC in RRMS, thereby creating a baseline for comparisons with future treatments. Methods Searches were completed in 14 databases, including MEDLINE, Embase, CENTRAL, CDSR and DARE, from inception to June 2018 to identify published or unpublished prospective, randomised controlled trials of all European Union-approved DMTs or DMTs expected to be approved in the near future in RRMS or rapidly-evolving severe RRMS. No language or date restrictions were applied. Studies were included in the MTC if they were judged to have sufficiently similar characteristics, based on the following: patient age; proportion of male participants; Expanded Disability Status Scale (EDSS) score; duration of disease; number of relapses prior to enrolment and proportion of previously treated patients. Background information from the included studies, as well as effect size and confidence intervals (where relevant) of defined outcomes were extracted. Reporting of the MTC was consistent with the International Society for Pharmacoeconomics and Outcomes Research (ISPOR) and Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) network meta-analysis guidelines. Results In total, 33 studies were included in the MTC. Annualised relapse rate (ARR 28 trials) was significantly reduced in all treatments compared with placebo. Alemtuzumab had the highest probability (63%) of being the most effective treatment in terms of ARR compared with placebo (rate ratio [RR] 0.28, 95% credible interval [CrI] 0.21–0.38), followed by natalizumab (30% probability; RR 0.32, 95% CrI 0.23–0.43). The risk of 3- and 6-month confirmed disability progression (CDP3M, 13 trials; CDP6M, 14 trials) were similar; CDP6M was significantly reduced for alemtuzumab (hazard ratio [HR] 0.365; 95% CrI 0.165–0.725), ocrelizumab (HR 0.405, 95% CrI 0.188–0.853) and natalizumab (HR 0.459, 95% CrI 0.252–0.840) relative to placebo. There were no significant differences in the odds of serious adverse events (SAEs, 6 trials) between any treatment and placebo. The results of the MTC were limited by the lack of studies reporting direct comparisons between the included treatments and by heterogeneous reporting of key outcome data. Conclusions Meta-analyses confirmed the benefit of all DMTs in terms of relapse rate compared with placebo with a comparable rate of SAEs for the DMTs that could be included in the network. The rigor and transparency of reporting in this study provide a benchmark for comparisons with future new agents.

Algae-based products have applications in the food and pharmaceutical industries, bioremediation of waste streams and biofuel production. Drying has been recognised to constitute the largest energy cost in algae processing, yet there is limited data or modelling characterising the drying kinetics of macroalgae. This research modelled the equilibrium moisture content of two macroalgae species, Ulva ohnoi, a saltwater alga and Oedogonium intermedium, a freshwater alga. The Guggenheim–Anderson–de Boer model was found to best represent experimental equilibrium moisture contents. Drying rate curves obtained under both convective and radiative conditions were fitted to an analytical solution of Fick’s second law, including the modelled equilibrium moisture values. Effective diffusivity values for the two species are presented.

Multiple myeloma is a cancer of the bone marrow that can induce bone disease. Here, the authors profile the transcriptome of bone-lining cells and find a targetable role of bone morphogenetic protein (BMP) signalling in myeloma-induced bone-disease

A new cave-dwelling dipluran of the North American endemic genus Haplocampa is described, coming from a couple of caves excavated in a small limestone karstic area near Port Alberni, Vancouver Island (British Columbia, Canada). To Haplocampa belong five soil-dwelling species. L. M. Ferguson cited no less than eight more species living in soil and cave habitats in several US states but without producing any formal descriptions. Haplocampa, in spite of its large lateral crests on the unequal claws, has clear taxonomical features as a Campodeinae and is closely related with the cave-dwelling Pacificampa and Eumesocampa genera, due to sharing similar macrosetae body distribution and absence or reduction of the lateral process. The new proposed species, Haplocampa wagnelli Sendra, sp. n., is rather interesting for its troglomorphic features: antennae with 32 antennomeres; olfactory chemoreceptors, each a multiperforated, folded-spiral structure; and numerous gouge sensilla. In addition, it is one of the northernmost troglomorphic species to have colonised – presumably recently – an area occupied by the Late Wisconsinian North America ice sheet during the Last Glacial Maximum. Furthermore, the close affinities between Haplocampa, Pacificampa (from caves in the extreme east of continental Asia and the southern Japanese Islands), Metriocampa (from the east of Asia and North America) and Eumesocampa (endemic to North America) suggest probable dispersal events over the Bering Land Bridge.

The same anthelmintic treatment can have variable efficacy on individual animals even if the parasite population is homogenously susceptible. An extension of the R package eggCounts is proposed to take individual efficacy into account using a Bayesian hierarchical model. A simulation study is conducted to compare the performance of five different methods on estimating faecal egg count reduction and its uncertainty interval. Simulation results showed the individual efficacy model offered robust inference to two different data simulation procedures with low root mean squared error on the reduction estimate and appropriate uncertainty estimates. Different methods were used to evaluate the anthelmintic resistance in a dataset from USA with sheep and cattle faecal egg counts, where a strong anthelmintic resistance was detected. Open-source statistical tools were updated to include the proposed model. Keywords: Bayesian hierarchical model, Statistical analysis, Faecal egg count reduction test, Anthelmintic resistance, Simulation study

BackgroundEfficient shoulder movement depends on the ability of central nervous system to integrate sensory information and to create an appropriate motor command. Various daily encountered factors can potentially compromise the execution of the command, such as fatigue. This study explored how fatigue influences shoulder movements during upper limb reaching.MethodsForty healthy participants were randomly assigned to one of two groups: Control or Fatigue Group. All participants completed an upper limb reaching task at baseline and post-experimental, during which they reached four targets located at 90° of shoulder abduction, 90° external rotation at 90° abduction, 120° scaption, and 120° flexion in a virtual reality environment. Following the baseline phase, the Fatigue Group completed a shoulder fatigue protocol, while Controls took a 10-minute break. Thereafter, the reaching task was repeated. Upper limb kinematic (joint angles and excursions) and spatiotemporal (speed and accuracy) data were collected during the reaching task. Electromyographic activity of the anterior and middle deltoids were also collected to characterize fatigue. Two-way repeated-measures ANOVA were performed to determine the effects of Time, Group and of the interaction between these factors.ResultsThe Fatigue group showed decreased mean median power frequency and increased electromyographic amplitudes of the anterior deltoid (p < 0.05) following the fatigue protocol. Less glenohumeral elevation, increased trunk flexion and rotation and sternoclavicular elevation were also observed in the Fatigue group (Group x Time interaction, p < 0.05). The Control group improved their movement speed and accuracy in post-experimental phase, while the Fatigue group showed a decrease of movement speed and no accuracy improvement (Group x Time interaction, p < 0.05).ConclusionIn a fatigued state, changes in movement strategy were observed during the reaching task, including increased trunk and sternoclavicular movements and less glenohumeral movement. Performance was altered as shown by the lack of accuracy improvement over time and a decrease in movement speed in the Fatigue group.

Nuclear factor (erythroid-derived 2) like 2 (NRF2) is a nuclear transcription factor activated in response to oxidative stress that induces a gene program that dampens inflammation and can limit cell damage that perpetuates the inflammatory response. We have identified A-1396076, a potent and selective NRF2 activator with demonstrated KEAP1 binding and modulation of cellular NRF2 mediated effects. In vivo administration of A-1396076 inhibits inflammation across several rodent models of autoimmunity when administered at or before the time of antigen challenge while also inducing NRF2 modulated gene transcription in the liver of the animals. It was not effective when administered after the time of antigen challenge or in a T cell independent model of arthritis induced by passive transfer of anti-collagen antibodies. A-1396076 inhibited antigen dependent T cell activation as measured by IFN-γ production in an ex vivo re-stimulation assay and following anti-CD3 challenge of MOG-sensitized mice. A-1396076 reduced costimulatory molecule expression on dendritic cells in the lungs of OVA LPS challenged mice suggesting that the mechanism of T cell inhibition was mediated at least partially by interfering with antigen presentation. These data suggest that NRF2 activation may be an effective strategy to dampen inflammation for treatment of autoimmune disease.

Summary: Background: Human cystic and alveolar echinococcosis are among the priority neglected zoonotic diseases for which WHO advocates control. The incidence of both cystic echinococcosis and alveolar echinococcosis has increased substantially in the past 30 years in Kyrgyzstan. Given the scarcity of adequate data on the local geographical variation of these focal diseases, we aimed to investigate within-country incidence and geographical variation of cystic echinococcosis and alveolar echinococcosis at a high spatial resolution in Kyrgyzstan. Methods: We mapped all confirmed surgical cases of cystic echinococcosis and alveolar echinococcosis reported through the national echinococcosis surveillance system in Kyrgyzstan between Jan 1, 2014, and Dec 31, 2016, from nine regional databases. We then estimated crude surgical incidence, standardised incidence, and standardised incidence ratios (SIRs) of primary cases (ie, excluding relapses) based on age and sex at country, region, district, and local community levels. Finally, we tested the SIRs for global and local spatial autocorrelation to identify disease hotspots at the local community level. All incidence estimates were calculated per 100 000 population and averaged across the 3-year study period to obtain annual estimates. Findings: The surveillance system reported 2359 primary surgical cases of cystic echinococcosis and 546 primary surgical cases of alveolar echinococcosis. Country-level crude surgical incidence was 13·1 per 100 000 population per year for cystic echinococcosis and 3·02 per 100 000 population per year for alveolar echinococcosis. At the local community level, we found annual crude surgical incidences up to 176 per 100 000 population in Sary-Kamysh (Jalal-Abad region) for cystic echinococcosis and 246 per 100 000 population in Uch-Dobo (Alay district, Osh region) for alveolar echinococcosis. Significant hotspots of cystic echinococcosis were found in four regions: Osh (five local communities in Uzgen district and four in Alay district), Naryn (three local communities in Jumgal district and one in Naryn district), Talas (three local communities in Talas district), and Chuy (one local community in Jayyl district). Significant alveolar echinococcosis hotspots were detected in the Osh region (11 communities in Alay district, including the local community of Sary Mogol, and one in Chong-Alay district) and in the Naryn region (five communities in Jumgal district and three in At-Bashy district), in the southwest and centre of the country. Interpretation: Our analyses reveal remarkable within-country variation in the surgical incidence of cystic echinococcosis and alveolar echinococcosis in Kyrgyzstan. These high-resolution maps identify precise locations where interventions and epidemiological research should be targeted to reduce the burden of human cystic echinococcosis and alveolar echinococcosis. Funding: Swiss National Science Foundation.

Interferon gamma (IFNγ) supports effector responses of CD8+ cytotoxic T lymphocytes (CTLs) and is a surrogate marker for detection of antigen-specific T cells. Here, we show that tumor-specific CTL clones have impaired IFNγ expression and production upon activation. Assessment of the relationship between IFNγ production and the 5′methylcytosine-guanine (CpG) dinucleotide methylation of the IFNγ promoter using bisulfite treatment has shown that IFNγ− CTL clones accumulates CpG hypermethylation within the promoter at key transcription factor binding sites (−186 and −54), known to be vital for transcription. We confirmed these findings using ex vivo isolated and short-term expanded bulk tumor-specific CTL lines from four cancer patients and demonstrated that IFNγ methylation inversely correlates with transcription, protein level, and cytotoxicity. Altogether, we propose that a sizeable portion of human tumor-specific CTLs are deficient in IFNγ response, contributed by CpG hypermethylation of the IFNγ promoter. Our findings have important implications for immunotherapy strategies and for methods to detect human antigen-specific T cells.

The conditions in which we are born, grow, live, work and age are key drivers of health and inequalities in life chances. To maximise health and wellbeing across the whole population, we need well-coordinated action across government sectors, in areas including economic, education, welfare, labour market and housing policy. Current research struggles to offer effective decision support on the cross-sector strategic alignment of policies, and to generate evidence that gives budget holders the confidence to change the way major investment decisions are made. This open letter introduces a new research initiative in this space. The SIPHER (Systems Science in Public Health and Health Economics Research) Consortium brings together a multi-disciplinary group of scientists from across six universities, three government partners at local, regional and national level, and ten practice partner organisations. The Consortium’s vision is a shift from health policy to healthy public policy, where the wellbeing impacts of policies are a core consideration across government sectors. Researchers and policy makers will jointly tackle fundamental questions about: a) the complex causal relationships between upstream policies and wellbeing, economic and equality outcomes; b) the multi-sectoral appraisal of costs and benefits of alternative investment options; c) public values and preferences for different outcomes, and how necessary trade-offs can be negotiated; and d) creating the conditions for intelligence-led adaptive policy design that maximises progress against economic, social and health goals. Whilst our methods will be adaptable across policy topics and jurisdictions, we will initially focus on four policy areas: Inclusive Economic Growth, Adverse Childhood Experiences, Mental Wellbeing and Housing.

Background: Cancer patients often display dysfunctional antitumor T-cell responses. Because noteworthy benefits of immune checkpoint pathway blockade, such as programmed cell death protein 1 (PD-1) inhibitors, have been achieved in multiple advanced cancers, the next critical question is which mono-blockade or combinatorial blockade regimens may reinvigorate antitumor T-cell immunity in those cancer patients while limiting immune-related adverse effects.Method: This study recruited, in total, 172 primary cancer patients (131 were blood-tumor-matched patients) who were treatment-naïve prior to the surgeries or biopsies covering the eight most prevalent types of cancer. With access to fresh surgical samples, this study simultaneously investigated the ex vivo expression level of eight known immune checkpoint receptors [PD-1, cytotoxic T-lymphocyte antigen-4 [CTLA-4], T-cell immunoglobulin and mucin-domain containing-3 [Tim-3], 2B4, killer cell lectin like receptor G1 [KLRG-1], TIGIT, B- and T-lymphocyte attenuator [BTLA], and CD160] on tumor-infiltrating T cells (TILs) and paired circulating T cells in blood from a 131-patient cohort.Results: We found increased an expression of PD-1 and Tim-3 but a decreased expression of BTLA on TILs when compared with peripheral blood from multiple types of cancer. Moreover, our co-expression analysis of key immune checkpoint receptors delineates “shared” subsets as PD-1+Tim-3+TIGIT+2B4+KLRG-1–CTLA-4– and PD-1+TIGIT+2B4+Tim-3–KLRG-1–CTLA-4– from bulk CD8 TILs. Furthermore, we found that a higher frequency of advanced differentiation stage T cells (CD27–CCR7–CD45RA–) among the “shared” subset (PD-1+Tim-3+TIGIT+2B4+KLRG-1–CTLA-4–) in bulk CD8 TILs was associated with poorly differentiated cancer type in cervical cancer patients.Conclusions: To our knowledge, our study is the first comprehensive analysis of key immune checkpoint receptors on T cells in treatment-naïve, primary cancer patients from the eight most prevalent types of cancer. These findings might provide useful information for future design of mono-blockade/combinatorial blockades and/or genetically modified T-cell immunotherapy.

Faced with the biggest virus outbreak in a century, world governments at the start of 2020 took unprecedented measures to protect their healthcare systems from being overwhelmed in the light of the COVID-19 pandemic. International travel was halted and lockdowns were imposed. Many nations adopted measures to stop the transmission of the virus, such as imposing the wearing of face masks, social distancing, and limits on social gatherings. Technology was quickly developed for mobile phones, allowing governments to track people’s movements concerning locations of the virus (both people and places). These are called contact tracing applications. Contact tracing applications raise serious privacy and security concerns. Within Europe, two systems evolved: a centralised system, which calculates risk on a central server, and a decentralised system, which calculates risk on the users’ handset. This study examined both systems from a threat perspective to design a framework that enables privacy and security for contact tracing applications. Such a framework is helpful for App developers. The study found that even though both systems comply with the General Data Protection Regulation (GDPR), Europe’s privacy legislation, the centralised system suffers from severe risks against the threats identified. Experiments, research, and reviews tested the decentralised system in various settings but found that it performs better but still suffers from inherent shortcomings. User tracking and re-identification are possible, especially when users report themselves as infected. Based on these data, the study identified and validated a framework that enables privacy and security. The study also found that the current implementations using the decentralised Google/Apple API do not comply with the framework.

Mexico, like many low- and middle-income countries (LMICs), faces an epidemic of chronic non-communicable diseases (NCDs), specifically diabetes, hypertension, obesity, and lipid disorders. Many people with these NCDs may not be aware that they have a disease, pointing to the need for broader screening programs. The traditional prevention policy in Mexico was based on screening with a paper-based risk factor questionnaire. However, this was used to screen patients already seeking healthcare services at facilities, and screening goals were set as a function of the number of questionnaires applied, not number of individuals screened. Due to this, Fundación Carlos Slim developed Medición Integrada para la Detección Oportuna (MIDOTM), or Integrated Measurement for Early Detection, an NCD screening and proactive prevention policy. This document is a policy analysis based on early learnings from the initial implementation of MIDO in eight primary healthcare centers in two central Mexican states. MIDO was found to expand screening programs beyond clinic walls, systematize community screening strategies, emphasize the detection of pre-disease phases, incorporate lifestyle counseling, and propose screening goals based on population targets. In collaboration with the Mexican Ministry of Health, MIDO has successfully screened over 500 000 individuals—about 40% of whom would not have been screened under previous policies. Of these more than 500 000 screened individuals, 13.4% had pre-diabetes (fasting glucose between 100 and 125 mg/dL), and 5.8% had undiagnosed diabetes (defined as fasting glucose above 126 mg/dL or random glucose above 200 mg/dL). However, there is still room for improvement in linking positive results from screening with disease confirmation and with patient incorporation into disease management. The experience of implementing MIDO in Mexico suggests that primary and secondary prevention programs in other parts of the world should consider the need for population-based screening targets, a greater focus on pre-disease stages, and the streamlining of the transition between screening, confirmation of diagnosis, and incorporation of patients into the healthcare system.

This paper sets out to make a contribution to the extensive literature that seeks to develop methods that allow rigorous and robust analysis of the spatial and temporal impacts of public policy interventions on property (real-estate) values. It argues that the hybrid repeat-sales/hedonic method developed in real-estate studies over the last 30 years has considerable, but as yet under-developed, potential as a policy analysis tool. Using data from Glasgow, UK, the empirical analysis illustrates how the technique can be used to understand the spatial spillovers and the dynamic temporal effects of a historic £100 million state-led, area-based, urban-renewal programme, New Life for Urban Scotland. The paper concludes by arguing that, with the rise in the availability of rich geocoded, micro-datasets, this framework is sufficiently flexible to be used to evaluate the real-estate market impacts of a wide range of public policy interventions. Significantly, as the case study demonstrates, the framework overcomes some of the sustained criticisms of the more commonly used hedonic modelling approach. There is, however, still much to do to enhance the technical qualities of the models through further application.

This document outlines the principles and practices of fertilizing freshwater fish ponds to enhance their productivity. Fertilization, akin to its use in land-based agriculture, can significantly boost the production of small natural food-consuming fish species such as bluegill and golden shiner by increasing the availability of algae and zooplankton. This process not only supports small fish but also benefits larger predatory fish, like largemouth bass, by improving their food supply. Phosphorus is identified as the most critical nutrient, often supplemented with nitrogen for better results. The document discusses the forms and application methods of fertilizers, emphasizing liquid fertilizers for their rapid effectiveness. Practical guidelines for determining the timing and frequency of fertilization based on water temperature and clarity are provided, alongside techniques for applying both liquid and granular fertilizers efficiently. The document also addresses common challenges such as muddy water, aquatic weeds, water exchange, and low alkalinity, and offers solutions for each. Finally, it highlights the importance of a committed, long-term fertilization program to avoid inefficiencies and aquatic weed issues. First published June 1990.

Tilapia lake virus is a globally emerging virus responsible for episodes of mass mortality in cultured and/or feral tilapia (Oreochromis spp. and hybrids) in Asia, Africa, Central America, and South America. Since 2014, there have been global reports of TiLV disease resulting in 10% to 90% mortality in tilapia fry, juveniles, and adults causing significant economic losses. Currently, the disease has been confirmed in Colombia, Ecuador, Egypt, India, Indonesia, Israel, Malaysia, Mexico, Philippines, Peru, Tanzania, and Thailand. TiLV has not yet been found in the USA or Canada, but it has most recently been reported in 20 aquaculture production facilities across six Mexican states (Chiapas, Jalisco, Michoacán, Sinaloa, Tabasco and Veracruz). This 7-page fact sheet written by Lowia Al-Hussinee, Kuttichantran Subramaniam, Win Surachetpong, Vsevolod Popov, Kathleen Hartman, Katharine Starzel, Roy Yanong, Craig Watson, Hugh Ferguson, Salvatore Frasca Jr., and Thomas Waltzek and published by the UF/IFAS School of Forest Resources and Conservation, Program in Fisheries and Aquatic Sciences describes this important emerging disease and explains how to prevent outbreaks and what to do if you suspect TiLV in an aquaculture facility or in the wild. http://edis.ifas.ufl.edu/fa213

We present a fully-integrated solution for controlling pneumatically-driven microfluidic chips, featuring a pump, one or more pressure regulators and up to 32 solenoid valves, controlled by a microcontroller. The microfluidics control system requires only a power source and a computer or mobile device for its operation. A touchscreen interface communicates with the microcontroller over USB or Bluetooth and allows users to control the system with ease either manually or autonomously, allowing experiments to run with no user intervention. The pressure regulators were purpose-built, enabling integrated pressure sources on-board, rather than relying on external equipment. These regulators can also be used as stand-alone devices in any other application. Keywords: Solenoid valve, Pressure regulator, Pressure controller, PDMS, Arduino, ESP32

Introduction: The association between geographic factors, including transport distance, and pediatric emergency medical services (EMS) run clustering on out-of-hospital pediatric endotracheal intubation is unclear. The objective of this study was to determine if endotracheal intubation procedures are more likely to occur at greater distances from the hospital and near clusters of pediatric calls. Methods: This was a retrospective observational study including all EMS runs for patients less than 18 years of age from 2008 to 2014 in a geographically large and diverse Oregon county that includes densely populated urban areas near Portland and remote rural areas. We geocoded scene addresses using the automated address locator created in the cloud-based mapping platform ArcGIS, supplemented with manual address geocoding for remaining cases. We then use the Getis-Ord Gi spatial statistic feature in ArcGIS to map statistically significant spatial clusters (hot spots) of pediatric EMS runs throughout the county. We then superimposed all intubation procedures performed during the study period on maps of pediatric EMS-run hot spots, pediatric population density, fire stations, and hospitals. We also performed multivariable logistic regression to determine if distance traveled to the hospital was associated with intubation after controlling for several confounding variables. Results: We identified a total of 7,797 pediatric EMS runs during the study period and 38 endotracheal intubations. In univariate analysis we found that patients who were intubated were similar to those who were not in gender and whether or not they were transported to a children’s hospital. Intubated patients tended to be transported shorter distances and were older than non-intubated patients. Increased distance from the hospital was associated with reduced odds of intubation after controlling for age, sex, scene location, and trauma system entry status in a multivariate logistic regression. The locations of intubations were superimposed on hot spots of all pediatric EMS runs. This map demonstrates that most of the intubations occurred within areas where pediatric EMS calls were highly clustered. By mapping the intubation procedures and pediatric population density, we found that intubation procedures were not clustered in a similar distribution to the pediatric population in the county. Conclusion: In this geographically diverse county the location of intubation procedures was similar to the clustering of pediatric EMS calls, and increased distance from the hospital was associated with reduced odds of intubation after controlling for several potential confounding variables.

A three-dimensional (3-D) finite-difference time-domain (FDTD) algorithm is used in order to simulate ground penetrating radar (GPR) for landmine detection. Two bowtie GPR transducers are chosen for the simulations and two widely employed antipersonnel (AP) landmines, namely PMA-1 and PMN are used. The validity of the modeled antennas and landmines is tested through a comparison between numerical and laboratory measurements. The modeled AP landmines are buried in a realistically simulated soil. The geometrical characteristics of soil's inhomogeneity are modeled using fractal correlated noise, which gives rise to Gaussian semivariograms often encountered in the field. Fractals are also employed in order to simulate the roughness of the soil's surface. A frequency-dependent complex electrical permittivity model is used for the dielectric properties of the soil, which relates both the velocity and the attenuation of the electromagnetic waves with the soil's bulk density, sand particles density, clay fraction, sand fraction, and volumetric water fraction. Debye functions are employed to simulate this complex electrical permittivity. Background features like vegetation and water puddles are also included in the models and it is shown that they can affect the performance of GPR at frequencies used for landmine detection (0.5-3 GHz). It is envisaged that this modeling framework would be useful as a testbed for developing novel GPR signal processing and interpretations procedures and some preliminary results from using it in such a way are presented.

The way in which electromagnetic fields are transmitted and received by ground penetrating radar (GPR) antennas is crucial to the performance of GPR systems. Simple antennas have been characterized by analyzing their radiation patterns and directivity. However, there have been limited studies that combine real GPR antennas with realistic environments, which is essential to capture the complex interactions between the antenna and surroundings. We have investigated the radiation characteristics and sensitivity of a GPR antenna in a range of lossy dielectric environments using both physical measurements and a three-dimensional (3-D) finite-difference time-domain (FDTD) model. Experimental data were from measured responses of a target positioned at intervals on the circumference of a circle surrounding the H-plane of the antenna. A series of oil-in-water emulsions as well as tap water were used to simulate homogeneous materials with different permittivities and with complex conductivities. Numerical radiation patterns were created utilizing a detailed 3-D FDTD model of the antenna. Good correlation was shown between the experimental results and modeled data with respect to the strength of the main lobe within the critical angle window. However, there are discrepancies in the strength of main lobe at shallow angles. In all the dielectrics, the main lobes are generally broad due to the near-field observation distance but, as expected, become narrower with increasing permittivity. These results provide confidence for further use of the FDTD antenna model to investigate scenarios such as larger observation distances and heterogeneous environments that are difficult to study experimentally.

The methods of data collection, processing, and assessment of the quality of the results of a survey conducted at the Southern Ionian Sea off the Messinian Peninsula, Greece are presented. Data were collected by the GEBCO-Nippon Foundation Alumni Team, competing in the Shell Ocean Discovery XPRIZE, during the Final Round of the competition. Data acquisition was conducted by the means of unmanned vehicles only. The mapping system was composed of a single deep water AUV (Autonomous Underwater Vehicle), equipped with a high-resolution synthetic aperture sonar HISAS 1032 and multibeam echosounder EM 2040, partnered with a USV (Unmanned Surface Vessel). The USV provided positioning data as well as mapping the seafloor from the surface, using a hull-mounted multibeam echosounder EM 304. Bathymetry and imagery data were collected for 24 h and then processed for 48 h, with the extensive use of cloud technology and automatic data processing. Finally, all datasets were combined to generate a 5-m resolution bathymetric surface, as an example of the deep-water mapping capabilities of the unmanned vehicles’ cooperation and their sensors’ integration.

In Turkey, there has been a strong policy narrative that has emphasized the importance of construction activity as a driver of economic growth. This has given shape to a central state-led policy regime that has sought to ensure that planners and other urban policy makers develop plans and strategies that support construction activity. Against this backdrop, and a recent history of uneven spatial development, this paper seeks to understand what this policy imperative might mean for housing construction activity in different provinces. It seeks to reflect on both the relationship between the state and the market, and the interaction between state policies, economic drivers and levels of construction activity. The evidence presented in the paper suggests that uneven spatial development might be explained in different ways in different provinces. Although, in many cases, patterns of construction activity are consistent with economic fundamentals, there are important exceptions in some regions where arguably activity levels are at odds with prior expectations.

In 2015 the International Conference on Health Promoting Universities and Colleges was held in the Okanagan, Canada. At this conference, a new international charter focusing on health promotion in tertiary education was ratified. The Okanagan Charter was developed with input from 45 countries, including Aotearoa New Zealand and Australia. The Okanagan Charter builds on existing charters and declarations to apply health, wellbeing and sustainability to tertiary settings. This paper outlines how the Okanagan Charter relates to health promotion approaches that are used in Aotearoa New Zealand in higher (tertiary) education for the benefit of students, staff and stakeholders. The principles and action areas of the Okanagan Charter are discussed in their application to health promotion practice in the higher education setting of Aotearoa New Zealand.

The Paris Agreement of the United Nation Framework Convention on Climate Change calls for a balance of anthropogenic greenhouse emissions and removals in the latter part of this century. Mexico indicated in its Intended Nationally Determined Contribution and its Climate Change Mid-Century Strategy that the land sector will contribute to meeting GHG emission reduction goals. Since 2012, the Mexican government through its National Forestry Commission, with international financial and technical support, has been developing carbon dynamics models to explore climate change mitigation options in the forest sector. Following a systems approach, here we assess the biophysical mitigation potential of forest ecosystems, harvested wood products and their substitution benefits (i.e. the change in emissions resulting from substitution of wood for more emissions-intensive products and fossil fuels), for policy alternatives considered by the Mexican government, such as a net zero deforestation rate and sustainable forest management. We used available analytical frameworks (Carbon Budget Model of the Canadian Forest Sector and a harvested wood products model), parameterized with local input data in two contrasting Mexican states. Using information from the National Forest Monitoring System (e.g. forest inventories, remote sensing, disturbance data), we demonstrate that activities aimed at reaching a net-zero deforestation rate can yield significant CO _2 e mitigation benefits by 2030 and 2050 relative to a baseline scenario (‘business as usual’), but if combined with increasing forest harvest to produce long-lived products and substitute more energy-intensive materials, emissions reductions could also provide other co-benefits (e.g. jobs, illegal logging reduction). We concluded that the relative impact of mitigation activities is locally dependent, suggesting that mitigation strategies should be designed and implemented at sub-national scales. We were also encouraged about the ability of the modeling framework to effectively use Mexico’s data, and showed the need to include multiple sectors and types of collaborators (scientific and policy-maker communities) to design more comprehensive portfolios for climate change mitigation.

Paralytic shellfish poisoning results from consumption of seafood naturally contaminated by saxitoxin and its congeners, the paralytic shellfish toxins (PSTs). The levels of such toxins are regulated internationally, and maximum permitted concentrations in seafood have been established in many countries. A mouse bioassay is an approved method for estimating the levels of PSTs in seafood, but this is now being superseded in many countries by instrumental methods of analysis. Such analyses provide data on the levels of many PSTs in seafood, but for risk assessment, knowledge of the relative toxicities of the congeners is required. These are expressed as “Toxicity Equivalence Factors” (TEFs). At present, TEFs are largely based on relative specific activities following intraperitoneal injection in a mouse bioassay rather than on acute toxicity determinations. A more relevant parameter for comparison would be median lethal doses via oral administration, since this is the route through which humans are exposed to PSTs. In the present study, the median lethal doses of gonyautoxin 5, gonyautoxin 6, decarbamoyl neosaxitoxin and of equilibrium mixtures of decarbamoyl gonyautoxins 2&3, C1&2 and C3&4 by oral administration to mice have been determined and compared with toxicities via intraperitoneal injection. The results indicate that the TEFs of several of these substances require revision in order to more accurately reflect the risk these toxins present to human health.

Copper has been used for many years as a chemical tool in freshwater farm ponds and aquaculture operations. It is both an effective algicide and a parasite treatment. The problem with the use of copper is that there is a thin line that separates effective treatment levels from overdoses, which can kill fish. This fact sheet is designed to explain when copper is used, how it is used, and some precautions to take before using it. First published in 1989.

Primary Total Hip Arthroplasty (THA) has been a very effective surgical procedure, with improvements in design and clinical outcomes since the days of Sir John Charnley. [1-4] However, many implant femoral hip designs and surgical approaches have not been considered conservative for bone preservation. Insertion of a femoral stem in THA does alter the physiological loading of the femur. Often these altered loading conditions can and do lead to bone reaction (stress shielding) and loss of proximal bone. Proximal stress shielding occurs regardless of fixation method (cement, cementless). [5,6] This stress shielding and bone loss can lead to implant loosening and or breakage of the implant. In an attempt to reduce these boney changes some designers have advocated the conservative concept of “Neck Replacement” THA. [7-9] This paper is a review of past, present and future development within this narrow classification of Neck Replacement Arthroplasty with highlighted focus on the Silent™ Implant. Key Words: total hip arthroplasty, tissue-sparing, neck-preserving, and conservative approach.

Liming is an effective tool in fish production and pond management. However, lime is casually used to describe two different types of materials, used for very different purposes. Agricultural limestone refers to calcite (calcium carbonate) and dolomite (calcium magnesium carbonate). The calcium and magnesium components raise the total hardness of water, essential to the health of many aquatic species. The carbonate component raises the total alkalinity and the pH, buffering daily fluctuations in pH, increasing microbial activity in the pond soil, and increasing the availability of phosphorous to phytoplankton. Pond water with total alkalinity less than 20 ppm can benefit from liming. Hydrated lime (calcium hydroxide) is an inexpensive and effective pond sterilizer, raising the pH quickly and dramatically above tolerable levels for most aquatic organisms. It should be used carefully, avoiding contact to the applicator, and never used in ponds containing desirable fish. This document was published first time in June, 1997

In August 2009, the U.S. Department of Education announced opportunities for states and local educational agencies to vie for $3.5 billion in Title I School Improvement Grants targeted at turning around or closing down chronically low-achieving schools. To qualify for a portion of these funds, school districts were required to implement one of four remedies at schools where students chronically demonstrated poor academic performance. Evidence is provided showing that the mandated interventions are highly speculative, minimally effective, and overly restrictive.