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As interest in machine learning and its applications becomes more widespread, how to choose the best models and hyper-parameter settings becomes more important. This problem is known to be challenging for human experts, and consequently, a growing number of methods have been proposed for solving it, giving rise to the area of automated machine learning (AutoML). Many of the most popular AutoML methods are based on Bayesian optimization, which makes only weak assumptions about how modifying hyper-parameters effects the loss of a model. This is a safe assumption that yields robust methods, as the AutoML loss landscapes that relate hyper-parameter settings to loss are poorly understood. We build on recent work on the study of one-dimensional slices of algorithm configuration landscapes by introducing new methods that test n -dimensional landscapes for statistical deviations from uni-modality and convexity, and we use them to show that a diverse set of AutoML loss landscapes are highly structured. We introduce a method for assessing the significance of hyper-parameter partial derivatives, which reveals that most (but not all) AutoML loss landscapes only have a small number of hyper-parameters that interact strongly. To further assess hyper-parameter interactions, we introduce a simplistic optimization procedure that assumes each hyper-parameter can be optimized independently, a single time in sequence, and we show that it obtains configurations that are statistically tied with optimal in all of the n -dimensional AutoML loss landscapes that we studied. Our results suggest many possible new directions for substantially improving the state of the art in AutoML.

Given the common problem of missing data in real-world applications from various fields, such as remote sensing, ecology and meteorology, the interpolation of missing spatial and spatio-temporal data can be of tremendous value. Existing methods for spatial interpolation, most notably Gaussian processes and spatial autoregressive models, tend to suffer from (a) a trade-off between modelling local or global spatial interaction, (b) the assumption there is only one possible path between two points, and (c) the assumption of homogeneity of intermediate locations between points. Addressing these issues, we propose a value propagation-based spatial interpolation method called VPint, inspired by Markov reward processes (MRPs), and introduce two variants thereof: (i) a static discount (SD-MRP) and (ii) a data-driven weight prediction (WP-MRP) variant. Both these interpolation variants operate locally, while implicitly accounting for global spatial relationships in the entire system through recursion. We evaluated our proposed methods by comparing the mean absolute error, root mean squared error, peak signal-to-noise ratio and structural similarity of interpolated grid cells to those of 8 common baselines. Our analysis involved detailed experiments on a synthetic and two real-world datasets, as well as experiments on convergence and scalability. Empirical results demonstrate the competitive advantage of VPint on randomly missing data, where it performed better than baselines in terms of mean absolute error and structural similarity, as well as spatially clustered missing data, where it performed best on 2 out of 3 datasets.

The Chinese pond mussel, Sinanodonta woodiana, is non-native to European freshwater systems. Originating from Asia, it was brought to Europe in the 1970s and is now spreading across many countries. Management of the species is currently limited by a lack of information on the actual distribution and population characterisation of S. woodiana as well as on the co-occurrence of native mussels potentially resulting in competition. For this paper, we examined nine water systems in the German federal state of Bavaria with randomly observed and anecdotally reported S. woodiana occurrences. We recorded the density and biomass of S. woodiana and of the co-existing mussel species as well as the habitat characteristics. We found S. woodiana in eight water systems, co-existing with other native and invasive mussel species in seven of them. The distribution of S. woodiana was geographically widespread throughout Bavaria, indicating great invasion potential. In one fish pond, S. woodiana was the only mussel species occurring with the highest mean biomass (1286.0 ± 1067.7 g m−2) and with the biggest specimen (25.0 cm and 1616.0 g). The wide range of habitat variables matched the expectation of a wide ecological niche for the species. This study provides evidence that S. woodiana has already become established in many water systems in Bavaria, with fish ponds and fisheries management practises being a likely vector. To counteract this species and to conserve native mussel species, it is important to implement effective legislation, to take measures to eradicate this invasive mussel transnationally, and to raise public awareness.

To describe effects of the COVID-19 pandemic on older adults living in non-institutionalized settings in New York City (NYC) we used random digit dial sampling of landlines phones to sample then interview residents 70 years and older in NYC from December 2020–March 2021. Socio-demographic, health characteristics and effects of the COVID-19 pandemic were solicited. Of 676 respondents, the average age was 78, 60% were female, and 63% had ever been tested for SARS-CoV-2, with 12% testing positive. Sixty-three percent of respondents knew someone who had been diagnosed with COVID-19 and 51% reported knowing at least one person who had died from COVID-19. Eight percent of respondents reported sometimes or often not having enough to eat, with 31% receiving food from a food pantry program. Significantly more Latinx respondents (24%) reported a positive SARS-CoV-2 test, whereas 17% of those of another race, 8% of white, and 7% of Black respondents had a positive COVID-19 test (p

Supplementary figure 2. Tumor gene expression changes measured by RT-PCR from mice treated with trametinib (T) in combination with the immunomodulator-targeting PD1 in the CT26 murine syngeneic model.

Supplementary figure 1. Tumor growth kinetics in individual mice treated with trametinib (T) in combination with the immunomodulator-targeting PD1 in the CT26 murine syngeneic model.

Purpose: Immunotherapeutic agents produce antitumor effects by inducing cancer-specific immune responses or by modifying native immune processes. Resulting clinical response patterns extend beyond those of cytotoxic agents and can manifest after an initial increase in tumor burden or the appearance of new lesions (progressive disease). Response Evaluation Criteria in Solid Tumors or WHO criteria, designed to detect early effects of cytotoxic agents, may not provide a complete assessment of immunotherapeutic agents. Novel criteria for the evaluation of antitumor responses with immunotherapeutic agents are required.Experimental Design: The phase II clinical trial program with ipilimumab, an antibody that blocks CTL antigen-4, represents the most comprehensive data set available to date for an immunotherapeutic agent. Novel immune therapy response criteria proposed, based on the shared experience from community workshops and several investigators, were evaluated using data from ipilimumab phase II clinical trials in patients with advanced melanoma.Results: Ipilimumab monotherapy resulted in four distinct response patterns: (a) shrinkage in baseline lesions, without new lesions; (b) durable stable disease (in some patients followed by a slow, steady decline in total tumor burden); (c) response after an increase in total tumor burden; and (d) response in the presence of new lesions. All patterns were associated with favorable survival.Conclusion: Systematic criteria, designated immune-related response criteria, were defined in an attempt to capture additional response patterns observed with immune therapy in advanced melanoma beyond those described by Response Evaluation Criteria in Solid Tumors or WHO criteria. Further prospective evaluations of the immune-related response criteria, particularly their association with overall survival, are warranted. (Clin Cancer Res 2009;15(23):7412–20)

The cytokine changes in mice receiving PI3K inhibition in combination with anti-OX40 treatment.

Supplementary Materials and Methods

In vivo effect of PI3K inhibition in combination with anti-OX40 treatment on T cell proliferation

The expression and function of OX40 on tumor-reactive T cells

Positively interaction of OX40 agonist antibody and PI3K inhibition in mice bearing PTEN-loss tumors

Purpose: To assess the immunologic effects of dabrafenib and trametinib in vitro and to test whether trametinib potentiates or antagonizes the activity of immunomodulatory antibodies in vivo.Experimental Design: Immune effects of dabrafenib and trametinib were evaluated in human CD4+ and CD8+ T cells from healthy volunteers, a panel of human tumor cell lines, and in vivo using a CT26 mouse model.Results: Dabrafenib enhanced pERK expression levels and did not suppress human CD4+ or CD8+ T-cell function. Trametinib reduced pERK levels, and resulted in partial/transient inhibition of T-cell proliferation/expression of a cytokine and immunomodulatory gene subset, which is context dependent. Trametinib effects were partially offset by adding dabrafenib. Dabrafenib and trametinib in BRAF V600E/K, and trametinib in BRAF wild-type tumor cells induced apoptosis markers, upregulated HLA molecule expression, and downregulated certain immunosuppressive factors such as PD-L1, IL1, IL8, NT5E, and VEGFA. PD-L1 expression in tumor cells was upregulated after acquiring resistance to BRAF inhibition in vitro. Combinations of trametinib with immunomodulators targeting PD-1, PD-L1, or CTLA-4 in a CT26 model were more efficacious than any single agent. The combination of trametinib with anti–PD-1 increased tumor-infiltrating CD8+ T cells in CT26 tumors. Concurrent or phased sequential treatment, defined as trametinib lead-in followed by trametinib plus anti–PD-1 antibody, demonstrated superior efficacy compared with anti–PD-1 antibody followed by anti–PD-1 plus trametinib.Conclusion: These findings support the potential for synergy between targeted therapies dabrafenib and trametinib and immunomodulatory antibodies. Clinical exploration of such combination regimens is under way. Clin Cancer Res; 21(7); 1639–51. ©2015 AACR.

Supplementary Figure legends

Purpose:OX40 agonist–based combinations are emerging as a novel avenue to improve the effectiveness of cancer immunotherapy. To better guide its clinical development, we characterized the role of the OX40 pathway in tumor-reactive immune cells. We also evaluated combining OX40 agonists with targeted therapy to combat resistance to cancer immunotherapy.Experimental Design: We utilized patient-derived tumor-infiltrating lymphocytes (TILs) and multiple preclinical models to determine the direct effect of anti-OX40 agonistic antibodies on tumor-reactive CD8+ T cells. We also evaluated the antitumor activity of an anti-OX40 antibody plus PI3Kβ inhibition in a transgenic murine melanoma model (Braf mutant, PTEN null), which spontaneously develops immunotherapy-resistant melanomas.Results:We observed elevated expression of OX40 in tumor-reactive CD8+ TILs upon encountering tumors; activation of OX40 signaling enhanced their cytotoxic function. OX40 agonist antibody improved the antitumor activity of CD8+ T cells and the generation of tumor-specific T-cell memory in vivo. Furthermore, combining anti-OX40 with GSK2636771, a PI3Kβ-selective inhibitor, delayed tumor growth and extended the survival of mice with PTEN-null melanomas. This combination treatment did not increase the number of TILs, but it instead significantly enhanced proliferation of CD8+ TILs and elevated the serum levels of CCL4, CXCL10, and IFNγ, which are mainly produced by memory and/or effector T cells.Conclusions:These results highlight a critical role of OX40 activation in potentiating the effector function of tumor-reactive CD8+ T cells and suggest further evaluation of OX40 agonist–based combinations in patients with immune-resistant tumors.

Supplementary tables S1-S6. Tumor gene expression data

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PDF file - 482K, Endogenous selectin ligands attenuate metastasis of B16-BL6 and 3LL cells (S1); Reconstitution of chimeric mice (S2); Leukocyte quantification in the lungs (S3); Detection of P-selectin ligands on monocytes and granulocytes (S4); Selectin ligand-expressing monocytes rescue metastasis of 3LL cells in Fuc-TVII -/- mice (S5); The absence of endogenous selectin ligands has no effect on expression levels of inflammatory cytokines (S6); Analysis of lung vascular permeability (S7); Fuc-TVII-/- mice accelerate primary tumor growth (S8); Transient depletion of neutrophils rescued metastasis in Fuc-TVII-/-mice (S9).

Tumor cell–derived selectin ligands mediate contact to the endothelium, platelets, and leukocytes through binding to selectins that facilitates metastasis. Here, we describe the mechanism of how endogenous (non–tumor derived) selectin ligands contribute to metastasis using α(1,3)fucosyltransferase 7 (Fuc-TVII−/−)–deficient mice. Experimental metastasis of MC-38GFP and Lewis lung (3LL) carcinoma cells was attenuated in Fuc-TVII−/− mice, which express minimal amount of selectin ligands. We show that metastasis is dependent on selectin ligands carried on hematopoietic cells. P-selectin glycoprotein ligand-1 (PSGL-1) was identified as the major ligand facilitating monocyte accumulation at metastatic sites. Reduced recruitment of monocytes to metastasizing tumor cells in Fuc-TVII−/− mice correlated with attenuated metastasis. Adoptive transfer of Fuc-T7+ monocytes rescued metastasis in Fuc-TVII−/− mice, indicating that selectin ligand–dependent recruitment of monocytes is required for cancer progression. Cytokine analysis in metastatic lungs revealed high expression of CCL2 in C57BL/6 mice that was significantly lower in Fuc-TVII−/− mice. The absence of monocyte recruitment in Fuc-TVII−/− mice correlated with increased apoptosis of tumor cells. Thus, the recruitment of monocytes to metastasizing tumor cells is facilitated by endogenous selectin ligands on monocytes that enable efficient tumor cell survival, extravasation, and metastasis. Cancer Res; 74(3); 695–704. ©2013 AACR.

PDF file - 18K, List of Primer Sequences used in the study.

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BackgroundViral acute respiratory tract infections (ARTIs) are a leading cause of hospitalization in infants and young children.MethodsDuring the winter seasons of 2014–2018, hospitalized children (ResultsOf 1353 children included in this study, 1142 (84.4%) were positive for ≥1 viral pathogen. Virus monoinfection was detected in 797 (69.8%) children, whereas 345 (30.2%) children had coinfections with 2–4 viral pathogens. Respiratory syncytial virus (RSV), rhinovirus, and influenza virus were the main pathogens detected. RSV-positive children had significantly more often lower ARTIs, including symptoms of severe cough, wheezing, chest indrawing, tachypnea, and pulmonary rales. Hospitalized children aged ConclusionsA better understanding of the etiology of viral ARTIs among hospitalized children plays a key role for future strategies in prevention, control, and treatment of respiratory viral infections.

International audience; Cyclic di-AMP is an essential signaling molecule in Gram-positive bacteria. This second messenger regulates the osmotic pressure of the cell by interacting directly with the regulatory domains, either RCK_C or CBS domains, of several potassium and osmolyte uptake membrane protein systems. Cyclic di-AMP also targets stand-alone CBS domain proteins such as DarB in Bacillus subtilis and CbpB in Listeria monocytogenes. We show here that the CbpB protein of Group B Streptococcus binds c-di-AMP with a very high affinity. Crystal structures of CbpB reveal the determinants of binding specificity and significant conformational changes occurring upon c-di-AMP binding. Deletion of the cbpB gene alters bacterial growth in low potassium conditions most likely due to a decrease in the amount of ppGpp caused by a loss of interaction between CbpB and Rel, the GTP/GDP pyrophosphokinase.

Freshwater bivalves are key faunal elements of aquatic ecosystems. Native species declines are paralleled by increasing distribution and abundances of non-native species. Appropriate management of both groups depends on knowledge of their interactions, which remains limited. Herein, we systematically review the current knowledge status of native and non-native bivalves in Europe, analyzing their functional interactions as well as niche and distribution overlaps between species. We also review existing management tools for non-native species in light of their applicability and sustainability. Strong and multiple interactions as well as niche overlaps between native and non-native bivalves already exist in Central Europe, especially with regard to Dreissena spp., Corbicula spp., and Sinanodonta woodiana. Direct competition is low with native species that have a high degree of specialization such as Margaritifera margaritifera, whereas the greatest niche overlap and competition occurs in generalist species such as Anadonta anatina, Unio pictorum, and S. woodiana. Early detection and preventive measures against undesired species are most successful in limiting their spread. Most methods for managing non-native species are unspecific and thus also include undesired side effects on endangered native species. The conservation and restoration of functionally intact bivalve habitats are the most sustainable and most resilient ways of management.

Earth observation (EO) is a prime instrument for monitoring land and ocean processes, studying the dynamics at work, and taking the pulse of our planet. This article gives a bird's eye view of the essential scientific tools and approaches informing and supporting the transition from raw EO data to usable EO-based information. The promises, as well as the current challenges of these developments, are highlighted under dedicated sections. Specifically, we cover the impact of (i) Computer vision; (ii) Machine learning; (iii) Advanced processing and computing; (iv) Knowledge-based AI; (v) Explainable AI and causal inference; (vi) Physics-aware models; (vii) User-centric approaches; and (viii) the much-needed discussion of ethical and societal issues related to the massive use of ML technologies in EO.

Additional file 1: Item description of the modified Standard for Reporting Diagnostic Accuracy Studies Guidelines for Heart Rate Variability Research (STARDHRV) by Dobbs et al. [69] based on Cohen et al. [70].

An international competition for negotiating agents has been organized for years to facilitate research in agent-based negotiation and to encourage the design of negotiating agents that can operate in various scenarios. The 13th International Automated Negotiating Agents Competition (ANAC 2022) was held in conjunction with IJCAI2022. In ANAC2022, we had two leagues: Automated Negotiation League (ANL) and Supply Chain Management League (SCML). For the ANL, the participants designed a negotiation agent that can learn from the previous bilateral negotiation sessions it was involved in. In contrast, the research challenge was to make the right decisions to maximize the overall profit in a supply chain environment, such as determining with whom and when to negotiate. This chapter describes the overview of ANL and SCML in ANAC2022, and reports the results of each league, respectively.

Background Iatrogenic Cushing’s syndrome induced by oral and parenteral glucocorticoid administration is a well-known complication. Immediate withdrawal from exogenous steroids can lead to life-threatening adrenal insufficiency. However, Cushing’s syndrome caused by topical treatment with glucocorticoids, such as dexamethasone eye drops or dermal application, is rarely recognized. Young infants in particular are at high risk of suffering from iatrogenic Cushing’s syndrome when treated with highly potent topical glucocorticoids. Case presentation We present a 6-month-old Syrian boy with cushingoid face after dermal clobetasol cream treatment and a 2-year-old Iranian girl with severe growth retardation after application of dexamethasone eye drops. Both families have a migration background and language barriers. In both cases no endogenous cortisol secretion was initially detected in serum and in 24-hour collected urine. After dose reduction of glucocorticoids, severity of symptoms was reversible and serum cortisol was detectable. Discussion and conclusion Young infants are at high risk of developing Cushing’s syndrome from topically applied highly potent glucocorticoids. Precise recommendations of treatment dosage, duration, and frequency must be given to the parents, and if necessary, with the help of an interpreter. Monitoring of height and weight as well as regular pediatric follow-ups should be scheduled. Physicians should be aware of potential adrenal insufficiency following withdrawal from long-term topical glucocorticoid treatment, and hydrocortisone treatment should be considered.

Water is essential for survival, but one in three individuals worldwide (2.2 billion people) lacks access to safe drinking water. Water intake requirements largely reflect water turnover (WT), the water used by the body each day. We investigated the determinants of human WT in 5604 people from the ages of 8 days to 96 years from 23 countries using isotope-tracking (2H) methods. Age, body size, and composition were significantly associated with WT, as were physical activity, athletic status, pregnancy, socioeconomic status, and environmental characteristics (latitude, altitude, air temperature, and humidity). People who lived in countries with a low human development index (HDI) had higher WT than people in high-HDI countries. On the basis of this extensive dataset, we provide equations to predict human WT in relation to anthropometric, economic, and environmental factors.

Total daily energy expenditure (“total expenditure”, MJ/d) reflects daily energy needs and is a critical variable in human health and physiology, yet it is unclear how daily expenditure changes over the life course. Here, we analyze a large, globally diverse database of total expenditure measured by the doubly labeled water method for males and females aged 8 days to 95 yr. We show that total expenditure is strongly related to fat free mass in a power-law manner and identify four distinct metabolic life stages. Fat free mass-adjusted daily expenditure accelerates rapidly in neonates (0-1yr) to ~46% above adult values at ~1 yr, declines slowly throughout childhood and adolescence (1-20 yr) to adult levels at ~20 yr, remains stable in adulthood (20-60 yr) even during pregnancy, and declines in older adults (60+ yr). These changes in total expenditure shed new light on human development and aging and should help shape nutrition and health strategies across the lifespan.

The potential of artificial intelligence (AI) applied to clinical data from electronic health records (EHRs) to improve early detection for pancreatic and other cancers remains underexplored. The Kenner Family Research Fund, in collaboration with the Cancer Biomarker Research Group at the National Cancer Institute, organized the workshop entitled: "Early Detection of Pancreatic Cancer: Opportunities and Challenges in Utilizing Electronic Health Records (EHR)" in March 2021. The workshop included a select group of panelists with expertise in pancreatic cancer, EHR data mining, and AI-based modeling. This review article reflects the findings from the workshop and assesses the feasibility of AI-based data extraction and modeling applied to EHRs. It highlights the increasing role of data sharing networks and common data models in improving the secondary use of EHR data. Current efforts using EHR data for AI-based modeling to enhance early detection of pancreatic cancer show promise. Specific challenges (biology, limited data, standards, compatibility, legal, quality, AI chasm, incentives) are identified, with mitigation strategies summarized and next steps identified.

BACKGROUND HIV population viral load (PVL) can reflect antiretroviral therapy program effectiveness and transmission potential in a community. Using nationally representative data from household surveys conducted in Zimbabwe, Malawi, and Zambia in 2015-16, we examined the association between various VL measures and the probability of at least one recent HIV-1 infection in the community. METHODS We used limiting-antigen avidity enzyme immunoassay, viral load suppression (VLS) (HIV RNA

Background The population-based HIV impact assessment (population-based HIV impact assessments) surveys are among the first to estimate national adult HIV incidence, subnational prevalence of viral load suppression, and pediatric HIV prevalence. We summarize the survey methods implemented in Zimbabwe, Malawi, and Zambia, as well as response rates and quality metrics. Methods Each cross-sectional, household-based survey used a 2-stage cluster design. Survey preparations included sample design, questionnaire development, tablet programming for informed consent and data collection, community mobilization, establishing a network of satellite laboratories, and fieldworker training. Interviewers collected demographic, behavioral, and clinical information using tablets. Blood was collected for home-based HIV testing and counseling (HBTC) and point-of-care CD4+ T-cell enumeration with results immediately returned. HIV-positive blood samples underwent laboratory-based confirmatory testing, HIV incidence testing, RNA polymerase chain reaction (viral load), DNA polymerase chain reaction (early infant diagnosis), and serum antiretroviral drug detection. Data were weighted for survey design, and chi square automatic interaction detection-based methods were used to adjust for nonresponse. Results Each survey recruited a nationally representative, household-based sample of children and adults over a 6-10-month period in 2015 and 2016. Most (84%-90%) of the 12,000-14,000 eligible households in each country participated in the survey, with 77%-81% of eligible adults completing an interview and providing blood for HIV testing. Among eligible children, 59%-73% completed HIV testing. Across the 3 surveys, 97.8% of interview data were complete and had no errors. Conclusion Conducting a national population-based HIV impact assessment with immediate return of HIV and other point-of-care test results was feasible, and data quality was high.

Metadata management is a crucial success factor for companies today, as for example, it enables exploiting data value fully or enables legal compliance. With the emergence of new concepts, such as the data lake, and new objectives, such as the enterprise-wide sharing of data, metadata management has evolved and now poses a renewed challenge for companies. In this context, we interviewed a globally active manufacturer to reveal how metadata management is implemented in practice today and what challenges companies are faced with and whether these constitute research gaps. As an outcome, we present the company’s metadata management goals and their corresponding solution approaches and challenges. An evaluation of the challenges through a literature and tool review yields three research gaps, which are concerned with the topics: (1) metadata management for data lakes, (2) categorizations and compositions of metadata management tools for comprehensive metadata management, and (3) the use of data marketplaces as metadata-driven exchange platforms within an enterprise. The gaps lay the groundwork for further research activities in the field of metadata management and the industry case represents a starting point for research to realign with real-world industry needs.

Fiber-reinforced composites are widely used in aerospace structures because of their high specific strength. However, the failure prediction in these heterogeneous engineered materials presents significant challenges due to the multiscale nature and interaction of the damage modes. The computational cost increases dramatically moving from coupon to element to subcomponent and higher levels of the building block ladder. Fine meshes and high-fidelity numerical models are necessary in order to achieve local accuracy but at the same time make the computations prohibitively expensive. The present work focuses on a practical approach, two-way global-local tight coupling, to allow users to setup the modeling easily and reduce the computational cost. This method can capture the global failure. Penalty connection method is used for tight coupling of the local and global regions. Multiple discrete damage modes are allowed in the local region. Two numerical examples are provided to illustrate that the two-way global-local tight coupling can effectively predict the local damage and the global response.

Achieving optimal HIV outcomes, as measured by global 90-90-90 targets, that is awareness of HIV-positive status, receipt of antiretroviral (ARV) therapy among aware and viral load (VL) suppression among those on ARVs, respectively, is critical. However, few data from sub-Saharan Africa (SSA) are available on older people (50+) living with HIV (OPLWH). We examined 90-90-90 progress by age, 15-49 (as a comparison) and 50+ years, with further analyses among 50+ (55-59, 60-64, 65+ vs. 50-54), in 13 countries (Cameroon, Cote d'Ivoire, Eswatini, Ethiopia, Kenya, Lesotho, Malawi, Namibia, Rwanda, Tanzania, Uganda, Zambia and Zimbabwe).Using data from nationally representative Population-based HIV Impact Assessments, conducted between 2015and 2019, participants from randomly selected households provided demographic and clinical information and whole blood specimens for HIV serology, VL and ARV testing. Survey weighted outcomes were estimated for 90-90-90 targets. Country-specific Poisson regression models examined 90-90-90 variation among OPLWH age strata.Analyses included 24,826 HIV-positive individuals (15-49 years: 20,170; 50+ years: 4656). The first, second and third 90 outcomes were achieved in 1, 10 and 5 countries, respectively, by those aged 15-49, while OPLWH achieved outcomes in 3, 13 and 12 countries, respectively. Among those aged 15-49, women were more likely to achieve 90-90-90 targets than men; however, among OPLWH, men were more likely to achieve first and third 90 targets than women, with second 90 achievement being equivalent. Country-specific 90-90-90 regression models among OPLWH demonstrated minimal variation by age stratum across 13 countries. Among OLPWH, no first 90 target differences were noted by age strata; three countries varied in the second 90 by older age strata but not in a consistent direction; one country showed higher achievement of the third 90 in an older age stratum.While OPLWH in these 13 countries were slightly more likely than younger people to be aware of their HIV-positive status (first 90), this target was not achieved in most countries. However, OPLWH achieved treatment (second 90) and VL suppression (third 90) targets in more countries than PLWH50. Findings support expanded HIV testing, prevention and treatment services to meet ongoing OPLWH health needs in SSA.

Aim of this project is to provide a systematic overview on all studies that determined HRVT during endurance exercise settings in healthy adults between an age of 18-60 years and that validated results compared to blood lactate or ventilatory thresholds. This overview will help decision making for sports practitioners and scientists when choosing threshold determination methods. Consequently, the further purposes of this review are to present the agreement of HRVT approaches with LT and VT approaches and to recommend suitable methods for common settings.

Relations between society and business are increasingly characterized by the societal demand for compliance with ethical standards. Companies are held responsible for behavior of their employees, which increases the demand for effective internal governance. To assure compliance, many companies enact codes of ethics. Despite a common core of ethical standards, codes differ considerably in formal design elements. Albeit theory suggests that a code's formal design, that is, how a code's content is presented, affects its behavioral impact, there is little research on this issue. Addressing this research gap, we conducted a between‐subjects experiment (factorial survey) in which we manipulated design elements of codes and examined how these elements affect behavioral intentions in various business situations. Holding the code's content constant, we manipulated its tone (positive vs. negative) and whether it was signed by the company's executive board (with vs. without signature). Our results indicate that the effectiveness of a code can be improved by using signed codes, while there is no effect for a code's tone. Our paper contributes designing internal governance in two ways: by giving experimental evidence on the relevance of a code's formal design and by providing practical guidance how to increase code effectiveness.

Zusammenfassung Hintergrund Eingangsuntersuchungen sind wichtig, um Aussagen über die Gesundheit treffen zu können. Diese Untersuchungen beinhalten etablierte internistisch-kardiologische Testverfahren sowie eine orthopädische Beurteilung des Bewegungsapparats. In den großen Mannschaftsportarten ist die Lizensierung der Spieler eng an die medizinischen Eingangsuntersuchungen geknüpft. Die vorgeschriebenen Eingangsuntersuchungen bilden jedoch lediglich den aktuellen Gesundheitszustand ab und lassen nur indirekte Aussagen über die Funktions- und Leistungsfähigkeit des Athleten zu. Somit wurde in den letzten Jahren versucht, diese Lücke durch eine Erweiterung in Richtung sportartspezifische Leistungsdiagnostik zu schließen. Sollte sich der Athlet verletzen, können die erhobenen Baseline-Werte als Maßstab genutzt werden, um das Monitoring des Sportlers im Rehabilitationsprozess zu unterstützen und einen sicheren Übergang zurück zum Wettkampf zu begleiten. Dies ist ein entscheidender Vorteil in der Return-to-Play-Diagnostik. Material und Methoden Aufgrund der Annahme, dass nur ein gesunder Spieler seine volle Leistungsfähigkeit abrufen kann, wurde von der Saison 2012/2013 für 5 aufeinanderfolgende Spielzeiten im Rahmen der medizinischen Eingangsuntersuchungen zusätzlich die Basketball-spezifische, konditionelle Leistungsfähigkeit der Spieler eines Basketball-Bundesligisten überprüft. Diese Werte wurden prospektiv mit den stattgehabten Verletzungen korreliert. Ergebnisse Insgesamt wurden 71 Spieler in jeweils 5 verschiedenen Kategorien (u. a. Sprungkraft, Agilität, Sprintfähigkeit) getestet. Im Untersuchungszeitraum ereigneten sich 142 Verletzungen, die im Mittel zu einer Ausfallzeit von 23 Tagen (Range 1–347 Tage) führten. Die Verletzungen betrafen zumeist die untere Extremität, wobei Sprunggelenk, Oberschenkel und Kniegelenk am häufigsten betroffen waren. Es zeigte sich ein deutlicher Trend dahingehend, dass Spieler mit einer schwächer ausgeprägten Richtungsänderungsschnelligkeit häufiger Verletzungen erlitten (r = 0,34; p = 0,029) und Spieler, die im YoYo-Test signifikant schlechter abschnitten, häufiger von Oberschenkelverletzungen betroffen waren (r = 0,266; p = 0,012). Schlussfolgerung Als Instrument zur Prävention sind medizinische Eingangsuntersuchungen nicht nur im Profisport essenziell, um Sportverletzungen oder Sportschäden aufzeigen bzw. ausschließen zu können. Die Erweiterung in Richtung sportartspezifische Leistungsdiagnostik liefert Informationen über Defizite bezogen auf Agilität und Ausdauer, die die Entstehung einer Verletzung begünstigen können. Darüber hinaus bieten die Untersuchungen auch die Möglichkeit, die erhobenen Werte als Baseline zu nutzen, die im Falle einer Verletzung den Fortschritt der Rehabilitation objektiv erfassbar machen und eine sichere Rückkehr zum Wettkampf ermöglichen.