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NASA’s all-sky survey mission, the Transiting Exoplanet Survey Satellite (TESS), is specifically engineered to detect exoplanets that transit bright stars. Thus far, TESS has successfully identified approximately 400 transiting exoplanets, in addition to roughly 6 000 candidate exoplanets pending confirmation. In this study, we present the results of our ongoing project, the Validation of Transiting Exoplanets using Statistical Tools (VaTEST). Our dedicated effort is focused on the confirmation and characterisation of new exoplanets through the application of statistical validation tools. Through a combination of ground-based telescope data, high-resolution imaging, and the utilisation of the statistical validation tool known as TRICERATOPS, we have successfully discovered eight potential super-Earths. These planets bear the designations: TOI-238b (1.61$^{+0.09} _{-0.10}$ R$_\oplus$), TOI-771b (1.42$^{+0.11} _{-0.09}$ R$_\oplus$), TOI-871b (1.66$^{+0.11} _{-0.11}$ R$_\oplus$), TOI-1467b (1.83$^{+0.16} _{-0.15}$ R$_\oplus$), TOI-1739b (1.69$^{+0.10} _{-0.08}$ R$_\oplus$), TOI-2068b (1.82$^{+0.16} _{-0.15}$ R$_\oplus$), TOI-4559b (1.42$^{+0.13} _{-0.11}$ R$_\oplus$), and TOI-5799b (1.62$^{+0.19} _{-0.13}$ R$_\oplus$). Among all these planets, six of them fall within the region known as ‘keystone planets’, which makes them particularly interesting for study. Based on the location of TOI-771b and TOI-4559b below the radius valley we characterised them as likely super-Earths, though radial velocity mass measurements for these planets will provide more details about their characterisation. It is noteworthy that planets within the size range investigated herein are absent from our own solar system, making their study crucial for gaining insights into the evolutionary stages between Earth and Neptune.
The number of studies on digital health technologies (DHTs) for remote treatment and patient self-management is increasing. Existing health technology assessment (HTA) frameworks for DHTs, which guide researchers in generating evidence suitable for HTA, do not cover all domains of the commonly used EUnetHTA Core Model, and DHT-specific considerations have not been informed by a large stakeholder preference study. Our aim was to develop a stakeholder prioritized, literature-informed checklist of DHT-specific considerations that aligns with the EUnetHTA model.
Methods
We conducted two systematic reviews to identify: (i) DHT evaluation frameworks published to March 2020 for content; and (ii) primary research on DHTs published from 1 January 2015 to 20 March 2020.
Stakeholder prioritization of issues was performed using a best-worst scaling preference study among a broad cross-section of patients, carers, health professionals, and the general population in Australia, Canada, New Zealand, and the UK. Systematic review issues were prioritized and adapted for use as a practical checklist.
Results
DHT evaluation content was recommended by the 44 identified frameworks for 28 of the 145 issues in the EUnetHTA model and for 22 new DHT-specific issues. A coverage assessment of 112 clinical studies of remote treatment and self-management DHTs for patients with cardiovascular disease or diabetes revealed that less than half covered DHT-specific content in all but one domain, or traditional HTA content in clinical effectiveness and ethical analysis. The preference survey of 1,251 stakeholders identified broad agreement on the 12 most important DHT attributes, six of which were related to safety. The most important attribute was “helps health professionals respond quickly when changes in patient care are needed”, which is not a focus of existing DHT HTA frameworks.
Conclusions
The review identified mismatches in the content generated by DHT clinical studies and that required for DHT-specific HTAs. These findings informed the development of an extended checklist comprising 22 stakeholder-prioritized DHT-specific considerations, which are aligned with the EUnetHTA model and will help ensure the planning of DHT-specific research generates evidence suitable for HTA.
Obesity is highly prevalent and disabling, especially in individuals with severe mental illness including bipolar disorders (BD). The brain is a target organ for both obesity and BD. Yet, we do not understand how cortical brain alterations in BD and obesity interact.
Methods:
We obtained body mass index (BMI) and MRI-derived regional cortical thickness, surface area from 1231 BD and 1601 control individuals from 13 countries within the ENIGMA-BD Working Group. We jointly modeled the statistical effects of BD and BMI on brain structure using mixed effects and tested for interaction and mediation. We also investigated the impact of medications on the BMI-related associations.
Results:
BMI and BD additively impacted the structure of many of the same brain regions. Both BMI and BD were negatively associated with cortical thickness, but not surface area. In most regions the number of jointly used psychiatric medication classes remained associated with lower cortical thickness when controlling for BMI. In a single region, fusiform gyrus, about a third of the negative association between number of jointly used psychiatric medications and cortical thickness was mediated by association between the number of medications and higher BMI.
Conclusions:
We confirmed consistent associations between higher BMI and lower cortical thickness, but not surface area, across the cerebral mantle, in regions which were also associated with BD. Higher BMI in people with BD indicated more pronounced brain alterations. BMI is important for understanding the neuroanatomical changes in BD and the effects of psychiatric medications on the brain.
Health service providers are currently making decisions on the public funding of digital health technologies (DHTs) for managing chronic diseases with limited understanding of stakeholder preferences for DHT attributes. This study aims to understand the community, patient/carer, and health professionals’ preferences to help inform a prioritized list of evaluation criteria.
Methods
An online best–worst scaling survey was conducted in Australia, New Zealand, Canada, and the United Kingdom to ascertain the relative importance of twenty-four DHT attributes among stakeholder groups using an efficient incomplete block design. The attributes were identified from a systematic review of DHT evaluation frameworks for consideration in a health technology assessment. Results were analyzed with multinomial models by stakeholder group and latent class.
Results
A total of 1,251 participants completed the survey (576 general community members, 543 patients/carers, and 132 health professionals). Twelve attributes achieved a preference score above 50 percent in the stakeholder group model, predominantly related to safety but also covering technical features, effectiveness, ethics, and economics. Results from the latent class model supported this prioritization. Overall, connectedness with the patient’s healthcare team seemed the most important; with “Helps health professionals respond quickly when changes in patient care are needed” as the most highly prioritized of all attributes.
Conclusions
It is proposed that these prioritized twelve attributes be considered in all evaluations of DHTs that manage chronic disease, supplemented with a limited number of attributes that reflect the specific perspective of funders, such as equity of access, cost, and system-level implementation considerations.
Evidence of Late Triassic large tetrapods from the UK is rare. Here, we describe a track-bearing surface located on the shoreline near Penarth, south Wales, United Kingdom. The total exposed surface is c. 50 m long and c. 2 m wide, and is split into northern and southern sections by a small fault. We interpret these impressions as tracks, rather than abiogenic sedimentary structures, because of the possession of marked displacement rims and their relationship to each other with regularly spaced impressions forming putative trackways. The impressions are large (up to c. 50 cm in length), but poorly preserved, and retain little information about track-maker anatomy. We discuss alternative, plausible, abiotic mechanisms that might have been responsible for the formation of these features, but reject them in favour of these impressions being tetrapod tracks. We propose that the site is an additional occurrence of the ichnotaxon Eosauropus, representing a sauropodomorph trackmaker, thereby adding a useful new datum to their sparse Late Triassic record in the UK. We also used historical photogrammetry to digitally map the extent of site erosion during 2009–2020. More than 1 m of the surface exposure has been lost over this 11-year period, and the few tracks present in both models show significant smoothing, breakage and loss of detail. These tracks are an important datapoint for Late Triassic palaeontology in the UK, even if they cannot be confidently assigned to a specific trackmaker. The documented loss of the bedding surface highlights the transient and vulnerable nature of our fossil resources, particularly in coastal settings, and the need to gather data as quickly and effectively as possible.
As health services increasingly make investment decisions in digital health technologies (DHTs), a DHT-specific and comprehensive health technology assessment (HTA) process is crucial in assessing value-for-money. Research in DHTs is ever-increasing, but whether it covers the content required for HTA is unknown.
Objectives
To summarize current trends in primary research on DHTs that manage chronic disease at home, particularly the coverage of content recommended for DHT-specific and comprehensive HTA.
Methods
Medline, Embase, Econlit, CINAHL, and The Cochrane Library (1 January 2015 to 20 March 2020) were searched for primary research studies using keywords related to DHT and HTA domains. Studies were assessed for coverage of the most frequently recommended content to be considered in a nine domain DHT-specific HTA previously developed.
Results
A total of 178 DHT interventions were identified, predominantly randomized controlled trials targeting cardiovascular disease/diabetes in high- to middle-income countries. A coverage assessment of the cardiovascular and diabetes DHT studies (112) revealed less than half covered DHT-specific content in all but the health problem domain. Content common to all technologies but essential for DHTs was covered by more than half the studies in all domains except for the effectiveness and ethical analysis domains.
Conclusions
Although DHT research is increasing, it is not covering all the content recommended for a DHT-specific and comprehensive HTA. The inability to conduct such an HTA may lead to health services making suboptimal investment decisions. Measures to increase the quality of trial design and reporting are required in DHT primary research.
A growing number of evaluation frameworks have emerged over recent years addressing the unique benefits and risk profiles of new classes of digital health technologies (DHTs). This systematic review aims to identify relevant frameworks and synthesize their recommendations into DHT-specific content to be considered when performing Health Technology Assessments (HTAs) for DHTs that manage chronic noncommunicable disease at home.
Methods
Searches were undertaken of Medline, Embase, Econlit, CINAHL, and The Cochrane Library (January 2015 to March 2020), and relevant gray literature (January 2015 to August 2020) using keywords related to HTA, evaluation frameworks, and DHTs. Included framework reference lists were searched from 2010 until 2015. The EUNetHTA HTA Core Model version 3.0 was selected as a scaffold for content evaluation.
Results
Forty-four frameworks were identified, mainly covering clinical effectiveness (n = 30) and safety (n = 23) issues. DHT-specific content recommended by framework authors fell within 28 of the 145 HTA Core Model issues. A further twenty-two DHT-specific issues not currently in the HTA Core Model were recommended.
Conclusions
Current HTA frameworks are unlikely to be sufficient for assessing DHTs. The development of DHT-specific content for HTA frameworks is hampered by DHTs having varied benefit and risk profiles. By focusing on DHTs that actively monitor/treat chronic noncommunicable diseases at home, we have extended DHT-specific content to all nine HTA Core Model domains. We plan to develop a supplementary evaluation framework for designing research studies, undertaking HTAs, and appraising the completeness of HTAs for DHTs.
Despite the strong link between childhood maltreatment and psychopathology, the underlying neurodevelopmental mechanisms are poorly understood and difficult to disentangle from heritable and prenatal factors. This study used a translational macaque model of infant maltreatment in which the adverse experience occurs in the first months of life, during intense maturation of amygdala circuits important for stress and emotional regulation. Thus, we examined the developmental impact of maltreatment on amygdala functional connectivity (FC) longitudinally, from infancy through the juvenile period. Using resting state functional magnetic resonance imaging (MRI) we performed amygdala–prefrontal cortex (PFC) region-of-interest and exploratory whole-brain amygdala FC analyses. The latter showed (a) developmental increases in amygdala FC with many regions, likely supporting increased processing of socioemotional-relevant stimuli with age; and (b) maltreatment effects on amygdala coupling with arousal and stress brain regions (locus coeruleus, laterodorsal tegmental area) that emerged with age. Maltreated juveniles showed weaker FC than controls, which was negatively associated with infant hair cortisol concentrations. Findings from the region-of-interest analysis also showed weaker amygdala FC with PFC regions in maltreated animals than controls since infancy, whereas bilateral amygdala FC was stronger in maltreated animals. These effects on amygdala FC development may underlie the poor behavioral outcomes associated with this adverse experience.
Numerical experiments, where a simple ice-sheet model was coupled with sediment-deformation models, were performed to investigate the transport of glacigenic material to the western Barents Shelf during the Late Weichselian. The ice-sheet model, and its environmental inputs, has been matched previously with a series of geological datasets relating to the maximum extent of the ice sheet (Howell and others, http://www.ggg.qub.ac.uk [rp05/1999]). Additional geological data on the volumes of sediment delivered to the Bear Island fan (Barents continental margin) are available for comparison. The experiments indicate the sensitivity of sediment transport and deposition to variations in (a) the ice-stream model and (b) a variety of model parameters. Two ice-stream models were used: (1) a height-above-buoyancy model, in which basal velocity is controlled by basal driving stress and a buoyancy-induced reduction in the normal load beneath a marine-based ice sheet; and (2) a modified version of the method presented by Alley (1990) in which basal velocity is related to pore-water pressure, sediment thickness, and driving basal stress. The results of the two different models were then compared. An extensive set of sensitivity tests was carried out to determine sediment-transport response to changes in the model’s parameters. Results indicate that, using physically realistic parameters for deforming subglacial sediment, both models reproduce the volume of Late Weichselian sediment measured on the Bear Island fan. Results from both models are sensitive to (1) cohesion of the sediment and (2) the thickness of deforming sediment beneath the ice sheet. The two models exhibited different degrees of sensitivity to the sediment parameters, with the height-above-buoyancy model proving to be less sensitive to variations in the thickness of the deforming sediment layer than the model proposed by Alley (1990). The differences between the two models examined here highlight the need for a comprehensive comparison of all the methodologies for calculating basal-ice motion currently in use.
A large-scale public health emergency, such as a severe influenza pandemic, can generate large numbers of critically ill patients in a short time. We modeled the number of mechanical ventilators that could be used in addition to the number of hospital-based ventilators currently in use.
Methods
We identified key components of the health care system needed to deliver ventilation therapy, quantified the maximum number of additional ventilators that each key component could support at various capacity levels (ie, conventional, contingency, and crisis), and determined the constraining key component at each capacity level.
Results
Our study results showed that US hospitals could absorb between 26,200 and 56,300 additional ventilators at the peak of a national influenza pandemic outbreak with robust pre-pandemic planning.
Conclusions
The current US health care system may have limited capacity to use additional mechanical ventilators during a large-scale public health emergency. Emergency planners need to understand their health care systems’ capability to absorb additional resources and expand care. This methodology could be adapted by emergency planners to determine stockpiling goals for critical resources or to identify alternatives to manage overwhelming critical care need. (Disaster Med Public Health Preparedness. 2015;9:634–641)
To evaluate Medical Reserve Corps volunteers and public health workers in conducting chronic care triage by use of a rubric prior to sheltering to connect survivors with services.
Methods
Participants were randomly assigned to 1 of 3 algorithms or a control group during a simulated disaster scenario and were asked to rate 20 survivors arriving at a chronic care triage station with situation-appropriate transport services. Survivors were simulated on the basis of the expected disability distributions of mobility, sensory-visual, cognition, medical devices, capacity to perform activities of daily living (ADLs), age (18 to 90 years), weight, and gender expected in the general population but expanded to 90% of those presenting. Mean percentage correct scores were assessed by using one-way analysis of variance.
Results
Accounting for personal care assistance and service methodology during chronic care triage increased efficiency by up to 8% in meeting chronic care health service needs during disaster community mass care management.
Conclusions
A chronic care triage process as part of community mass care management that considers the availability of personal care assistance and service methodology will enhance the allocation of functional needs support services and increase compliance with Americans with Disabilities Act requirements regarding not segregating persons because of disability. (Disaster Med Public Health Preparedness. 2015;9:265-274)
The Nakhla meteorite represents basaltic rock from the martian upper crust, with reduced carbon indicative of the ingress of carbonaceous fluids. Study of a terrestrial analogue basalt with reduced carbon from the Ordovician of Northern Ireland shows that remote analysis could detect the carbon using Raman spectroscopy. Analysis of gases released by crushing detects methane-rich fluids in the basalt and especially in cross-cutting carbon-bearing veinlets. The results suggest that automated analysis on Mars could detect the reduced carbon, which may be derived from magmatic and/or meteoritic infall sources.
Intermittent energy restriction may result in greater improvements in insulin sensitivity and weight control than daily energy restriction (DER). We tested two intermittent energy and carbohydrate restriction (IECR) regimens, including one which allowed ad libitum protein and fat (IECR+PF). Overweight women (n 115) aged 20 and 69 years with a family history of breast cancer were randomised to an overall 25 % energy restriction, either as an IECR (2500–2717 kJ/d, < 40 g carbohydrate/d for 2 d/week) or a 25 % DER (approximately 6000 kJ/d for 7 d/week) or an IECR+PF for a 3-month weight-loss period and 1 month of weight maintenance (IECR or IECR+PF for 1 d/week). Insulin resistance reduced with the IECR diets (mean − 0·34 (95 % CI − 0·66, − 0·02) units) and the IECR+PF diet (mean − 0·38 (95 % CI − 0·75, − 0·01) units). Reductions with the IECR diets were significantly greater compared with the DER diet (mean 0·2 (95 % CI − 0·19, 0·66) μU/unit, P= 0·02). Both IECR groups had greater reductions in body fat compared with the DER group (IECR: mean − 3·7 (95 % CI − 2·5, − 4·9) kg, P= 0·007; IECR+PF: mean − 3·7 (95 % CI − 2·8, − 4·7) kg, P= 0·019; DER: mean − 2·0 (95 % CI − 1·0, 3·0) kg). During the weight maintenance phase, 1 d of IECR or IECR+PF per week maintained the reductions in insulin resistance and weight. In the short term, IECR is superior to DER with respect to improved insulin sensitivity and body fat reduction. Longer-term studies into the safety and effectiveness of IECR diets are warranted.
Questionnaire surveys, while more economical, typically achieve poorer response rates than interview surveys. We used data from a national volunteer cohort of young adult twins, who were scheduled for assessment by questionnaire in 1989 and by interview in 1996-2000, to identify predictors of questionnaire non-response. Out of a total of 8536 twins, 5058 completed the questionnaire survey (59% response rate), and 6255 completed a telephone interview survey conducted a decade later (73% response rate). Multinomial logit models were fitted to the interview data to identify socioeconomic, psychiatric and health behavior correlates of non-response in the earlier questionnaire survey. Male gender, education below University level, and being a dizygotic rather than monozygotic twin, all predicted reduced likelihood of participating in the questionnaire survey. Associations between questionnaire response status and psychiatric history and health behavior variables were modest, with history of alcohol dependence and childhood conduct disorder predicting decreased probability of returning a questionnaire, and history of smoking and heavy drinking more weakly associated with non-response. Body-mass index showed no association with questionnaire non-response. Despite a poor response rate to the self-report questionnaire survey, we found only limited sampling biases for most variables. While not appropriate for studies where socioeconomic variables are critical, it appears that survey by questionnaire, with questionnaire administration by telephone to non-responders, will represent a viable strategy for gene-mapping studies requiring that large numbers of relatives be screened.
As we have noted before, the WG-IR was created following a Joint Commission Meeting at the IAU General Assembly in Baltimore in 1988, a meeting that provided both diagnosis and prescription for the perceived ailments of infrared photometry at the time. The results were summarized in Milone (1989). The challenges involve how to explain the failure to systematically achieve the milli-magnitude precision expected of infrared photometry and an apparent 3% limit on system transformability. The proposed solution was to re-define the broadband Johnson system, the passbands of which had proven so unsatisfactory that over time effectively different systems proliferated although bearing the same JHKLMNQ designations; the new system needed to be better positioned and centered in the atmospheric windows of the Earth's atmosphere, and the variable water vapour content of the atmosphere needed to be measured in real time to better correct for atmospheric extinction.
Re´sume´Parmi les ge`nes dont les produits jouent un rle critique dans la re´gulation de la re´ponse immune, on trouve les familles de ge`nes de l'antige`ne leucocyte humain (ALH) et de la cytokine. Les ge`nes ALH sont les plus polymorphes du ge´nome humain, et ce polymorphisme entraine des diffe´rences fonctionnelles des mole´cules ALH exprime´es, qui se traduit par des diffe´rences individuelles dans la manie`re dont des peptides antige´niques se pre´sentent aux cellules T. De plus, un nombre conside´rable de polymorphismes des ge`nes associe´s a la cytokine ont e´te´ identifie´s, la plupart d'entre eux se produisent au niveau du promoteur de ces ge`nes, ce que dans de nombreux cas se traduit par l'expression diffe´rentielle in vitro de leurs respectifs produits ge´ne´tiques pro- ou anti-inflammatoire. Des polymorphismes ALH particuliers aboutirent a` des associations bien de´finies avec un grand nombre de maladies immunologiquement medie´es, parmi lesquelles quelques-unes avec des facteurs de risque die´te´tique. Par exemple, des individus de ge´notype HLA-DQA1*0501, DQB1*0201 ont un risque deux cent fois plus grand de de´velopper une intole´rance au gluten alimentaire (maladie ce´liaque), et des facteurs additionnels en relation avec l'ALH peuvent influencer le de´veloppement d'un lymphome maligne dans une maladie ce´liaque existante. De mme, des alle`les HLA-DRB1 qui partage une se´quence motive commune constituent le premier facteur de risque ge´ne´tique de l'arthrite rhumatode. L'influence de polymorphismes associe´s a une expression de cytokine diffe´rentiel sur la susceptibilite´ aux maladies pre´sent dans ce moment un grand inte´rt. La plupart de l'attention a e´tait centre´ les associations avec la susceptibilite´ de maladies medie´es immunologiquement be´nignes, parmi eux un grand nombre de maladies de l'intestin. Toutefois, un travail re´cent dans notre laboratoire indique que les polymorphismes de la cytokine peuvent influencer la susceptibilite´ a` certains cancers (ainsi que son pronostic), entre eux le me´lanome de peau maligne et des tumeurs solides qui peuvent tre affecte´s par l'alimentation, comme le cancer de prostate (collaboration avec le CRC/BPG e´tude familial du cancer de prostate Royaume-Uni). De plus, des travails pre´liminaires sugge`rent que la modulation par l'alimentation des niveaux d'expression de certaines cytokines dans des sujets humains peut tre de´pendent du ge´notype.
It has been estimated that more than 50% of deaths before the age of 5 years have undernutrition as an underlying cause. Severe childhood malnutrition, an extreme form of undernutrition, occurs as oedematous and non-oedematous syndromes. The reasons why only some children develop oedematous severe childhood malnutrition (OSCM) have remained elusive, but the heterogeneity of clinical appearances among children from relatively homogeneous backgrounds suggests that interindividual variation in susceptibility to OSCM may exist. We investigated variants of four glutathione S-transferase (GST) genes in a retrospective study among subjects (n136) previously admitted to the Tropical Metabolism Research Unit, Jamaica, for the treatment of either OSCM (cases) or non-oedematous severe childhood malnutrition (controls). We found that GSTP1 Val105 homozygotes were significantly more common among the cases (odds ratio (OR) 3·5; 95% CI 1·1, 10·8). We also found an association of borderline significance between non-deletion GSTT1 genotypes (i.e. +/+ or +/0) and OSCM (OR 2·4; 95% CI 1·0, 5·9). There was no significant association between OSCM and any of the other GST variants. These preliminary findings suggest that genetic variation within the GST superfamily may contribute to the risk of OSCM. Additional, larger data sets and studies of variants in other candidate genes are required in order to properly assess the true contribution, if any, of genetic variation to risk of OSCM. Such studies may improve our understanding of the causes of clinical heterogeneity in malnutrition.