Exoplanet Atmosphere Measurements from Transmission Spectroscopy and other Planet-Star Combined Light Observations

It is possible to learn a great deal about exoplanet atmospheres even when we cannot spatially resolve the planets from their host stars. In this chapter, we overview the basic techniques used to characterize transiting exoplanets - transmission spectroscopy, emission and reflection spectroscopy, and full-orbit phase curve observations. We discuss practical considerations, including current and future observing facilities and best practices for measuring precise spectra. We also highlight major observational results on the chemistry, climate, and cloud properties of exoplanets.Comment: Accepted review chapter; Handbook of Exoplanets, eds. Hans J. Deeg and Juan Antonio Belmonte (Springer-Verlag). 22 pages, 6 figure

Plasma and CSF concentrations of N-terminal tau fragments associate with in vivo neurofibrillary tangle burden

INTRODUCTION: Fluid biomarkers capable of specifically tracking tau tangle pathology in vivo are greatly needed. METHODS: We measured cerebrospinal fluid (CSF) and plasma concentrations of N-terminal tau fragments (NTA-tau), using a novel immunoassay (NTA) in the TRIAD cohort, consisting of 272 individuals assessed with amyloid beta (Aβ) positron emission tomography (PET), tau PET, magnetic resonance imaging (MRI) and cognitive assessments. RESULTS: CSF and plasma NTA-tau concentrations were specifically increased in cognitively impaired Aβ-positive groups. CSF and plasma NTA-tau concentrations displayed stronger correlations with tau PET than with Aβ PET and MRI, both in global uptake and at the voxel level. Regression models demonstrated that both CSF and plasma NTA-tau are preferentially associated with tau pathology. Moreover, plasma NTA-tau was associated with longitudinal tau PET accumulation across the aging and Alzheimer's disease (AD) spectrum. DISCUSSION: NTA-tau is a biomarker closely associated with in vivo tau deposition in the AD continuum and has potential as a tau tangle biomarker in clinical settings and trials. HIGHLIGHTS: An assay for detecting N-terminal tau fragments (NTA-tau) in plasma and CSF was evaluated. NTA-tau is more closely associated with tau PET than amyloid PET or neurodegeneration. NTA-tau can successfully track in vivo tau deposition across the AD continuum. Plasma NTA-tau increased over time only in cognitively impaired amyloid-β positive individuals

biomArker-guided Duration of Antibiotic treatment in hospitalised Patients with suspecTed Sepsis (ADAPT-Sepsis): A protocol for a multicentre randomised controlled trial

AIM: To describe the protocol for a multi-centre randomised controlled trial to determine whether treatment protocols monitoring daily CRP (C-reactive protein) or PCT (procalcitonin) safely allow a reduction in duration of antibiotic therapy in hospitalised adult patients with sepsis. DESIGN: Multicentre three-arm randomised controlled trial. SETTING: UK NHS hospitals. TARGET POPULATION: Hospitalised critically ill adults who have been commenced on intravenous antibiotics for sepsis. HEALTH TECHNOLOGY: Three protocols for guiding antibiotic discontinuation will be compared: (a) standard care; (b) standard care + daily CRP monitoring; (c) standard care + daily PCT monitoring. Standard care will be based on routine sepsis management and antibiotic stewardship. Measurement of outcomes and costs. Outcomes will be assessed to 28 days. The primary outcomes are total duration of antibiotics and safety outcome of all-cause mortality. Secondary outcomes include: escalation of care/re-admission; infection re-lapse/recurrence; antibiotic dose; length and level of critical care stay and length of hospital stay. Ninety-day all-cause mortality rates will also be collected. An assessment of cost effectiveness will be performed. CONCLUSION: In the setting of routine NHS care, if this trial finds that a treatment protocol based on monitoring CRP or PCT safely allows a reduction in duration of antibiotic therapy, and is cost effective, then this has the potential to change clinical practice for critically ill patients with sepsis. Moreover, if a biomarker-guided protocol is not found to be effective, then it will be important to avoid its use in sepsis and prevent ineffective technology becoming widely adopted in clinical practice

Recommendations for a core outcome set for measuring standing balance in adult populations: a consensus-based approach

Standing balance is imperative for mobility and avoiding falls. Use of an excessive number of standing balance measures has limited the synthesis of balance intervention data and hampered consistent clinical practice.To develop recommendations for a core outcome set (COS) of standing balance measures for research and practice among adults.A combination of scoping reviews, literature appraisal, anonymous voting and face-to-face meetings with fourteen invited experts from a range of disciplines with international recognition in balance measurement and falls prevention. Consensus was sought over three rounds using pre-established criteria.The scoping review identified 56 existing standing balance measures validated in adult populations with evidence of use in the past five years, and these were considered for inclusion in the COS.Fifteen measures were excluded after the first round of scoring and a further 36 after round two. Five measures were considered in round three. Two measures reached consensus for recommendation, and the expert panel recommended that at a minimum, either the Berg Balance Scale or Mini Balance Evaluation Systems Test be used when measuring standing balance in adult populations.Inclusion of two measures in the COS may increase the feasibility of potential uptake, but poses challenges for data synthesis. Adoption of the standing balance COS does not constitute a comprehensive balance assessment for any population, and users should include additional validated measures as appropriate.The absence of a gold standard for measuring standing balance has contributed to the proliferation of outcome measures. These recommendations represent an important first step towards greater standardization in the assessment and measurement of this critical skill and will inform clinical research and practice internationally

Collocation analysis for UMLS knowledge-based word sense disambiguation

BACKGROUND: The effectiveness of knowledge-based word sense disambiguation (WSD) approaches depends in part on the information available in the reference knowledge resource. Off the shelf, these resources are not optimized for WSD and might lack terms to model the context properly. In addition, they might include noisy terms which contribute to false positives in the disambiguation results. METHODS: We analyzed some collocation types which could improve the performance of knowledge-based disambiguation methods. Collocations are obtained by extracting candidate collocations from MEDLINE and then assigning them to one of the senses of an ambiguous word. We performed this assignment either using semantic group profiles or a knowledge-based disambiguation method. In addition to collocations, we used second-order features from a previously implemented approach.Specifically, we measured the effect of these collocations in two knowledge-based WSD methods. The first method, AEC, uses the knowledge from the UMLS to collect examples from MEDLINE which are used to train a Naïve Bayes approach. The second method, MRD, builds a profile for each candidate sense based on the UMLS and compares the profile to the context of the ambiguous word.We have used two WSD test sets which contain disambiguation cases which are mapped to UMLS concepts. The first one, the NLM WSD set, was developed manually by several domain experts and contains words with high frequency occurrence in MEDLINE. The second one, the MSH WSD set, was developed automatically using the MeSH indexing in MEDLINE. It contains a larger set of words and covers a larger number of UMLS semantic types. RESULTS: The results indicate an improvement after the use of collocations, although the approaches have different performance depending on the data set. In the NLM WSD set, the improvement is larger for the MRD disambiguation method using second-order features. Assignment of collocations to a candidate sense based on UMLS semantic group profiles is more effective in the AEC method.In the MSH WSD set, the increment in performance is modest for all the methods. Collocations combined with the MRD disambiguation method have the best performance. The MRD disambiguation method and second-order features provide an insignificant change in performance. The AEC disambiguation method gives a modest improvement in performance. Assignment of collocations to a candidate sense based on knowledge-based methods has better performance. CONCLUSIONS: Collocations improve the performance of knowledge-based disambiguation methods, although results vary depending on the test set and method used. Generally, the AEC method is sensitive to query drift. Using AEC, just a few selected terms provide a large improvement in disambiguation performance. The MRD method handles noisy terms better but requires a larger set of terms to improve performance

Effect of household-based drinking water chlorination on diarrhoea among children under five in Orissa, India: a double-blind randomised placebo-controlled trial.

BACKGROUND: Boiling, disinfecting, and filtering water within the home can improve the microbiological quality of drinking water among the hundreds of millions of people who rely on unsafe water supplies. However, the impact of these interventions on diarrhoea is unclear. Most studies using open trial designs have reported a protective effect on diarrhoea while blinded studies of household water treatment in low-income settings have found no such effect. However, none of those studies were powered to detect an impact among children under five and participants were followed-up over short periods of time. The aim of this study was to measure the effect of in-home water disinfection on diarrhoea among children under five. METHODS AND FINDINGS: We conducted a double-blind randomised controlled trial between November 2010 and December 2011. The study included 2,163 households and 2,986 children under five in rural and urban communities of Orissa, India. The intervention consisted of an intensive promotion campaign and free distribution of sodium dichloroisocyanurate (NaDCC) tablets during bi-monthly households visits. An independent evaluation team visited households monthly for one year to collect health data and water samples. The primary outcome was the longitudinal prevalence of diarrhoea (3-day point prevalence) among children aged under five. Weight-for-age was also measured at each visit to assess its potential as a proxy marker for diarrhoea. Adherence was monitored each month through caregiver's reports and the presence of residual free chlorine in the child's drinking water at the time of visit. On 20% of the total household visits, children's drinking water was assayed for thermotolerant coliforms (TTC), an indicator of faecal contamination. The primary analysis was on an intention-to-treat basis. Binomial regression with a log link function and robust standard errors was used to compare prevalence of diarrhoea between arms. We used generalised estimating equations to account for clustering at the household level. The impact of the intervention on weight-for-age z scores (WAZ) was analysed using random effect linear regression. Over the follow-up period, 84,391 child-days of observations were recorded, representing 88% of total possible child-days of observation. The longitudinal prevalence of diarrhoea among intervention children was 1.69% compared to 1.74% among controls. After adjusting for clustering within household, the prevalence ratio of the intervention to control was 0.95 (95% CI 0.79-1.13). The mean WAZ was similar among children of the intervention and control groups (-1.586 versus -1.589, respectively). Among intervention households, 51% reported their child's drinking water to be treated with the tablets at the time of visit, though only 32% of water samples tested positive for residual chlorine. Faecal contamination of drinking water was lower among intervention households than controls (geometric mean TTC count of 50 [95% CI 44-57] per 100 ml compared to 122 [95% CI 107-139] per 100 ml among controls [p<0.001] [n = 4,546]). CONCLUSIONS: Our study was designed to overcome the shortcomings of previous double-blinded trials of household water treatment in low-income settings. The sample size was larger, the follow-up period longer, both urban and rural populations were included, and adherence and water quality were monitored extensively over time. These results provide no evidence that the intervention was protective against diarrhoea. Low compliance and modest reduction in water contamination may have contributed to the lack of effect. However, our findings are consistent with other blinded studies of similar interventions and raise additional questions about the actual health impact of household water treatment under these conditions. TRIAL REGISTRATION: ClinicalTrials.govNCT01202383 Please see later in the article for the Editors' Summary

Knowledge and perceptions of the risks of non-steroidal anti-inflammatory drugs among orthopaedic patients in Thailand

Background There is a high incidence of adverse effects from non-steroidal antiinflammatory drugs (NSAIDs) in Thailand, but patients’ perceptions and knowledge of NSAID risks is unknown. Objective This study aims to assess patients’ perceptions and knowledge of NSAID risks and factors affecting them. Setting University hospital in North-East of Thailand. Method A Cross-sectional study conducted over 4 months, using a self-administered questionnaire. Patients prescribed NSAIDs for at least one month duration from orthopaedic clinic were recruited using systematic random sampling. Main outcome measure Patients’ perceptions on NSAID risks, knowledge on risk factors, and their associated factors. Results A total of 474 questionnaires were assessed. Overall perceptions of risks was low (scoring below five on a 0–10 visual analogue scale), with risks associated with the renal system scoring highest. Perceived risk of gastrointestinal problems differed between patients using non-selective and selective NSAIDs (3.47 ± 2.75 vs 2.06 ± 2.98; P < 0.001). Receiving side effect information from a health professional was associated with higher risk perception. Most patients (80 %) identified high doses, renal disease and gastrointestinal ulcer increased risks of NSAIDs, but fewer than half recognized that use in the elderly, multiple NSAID use, drinking, hypertension and cardiovascular disease also increased risk of adverse events. Having underlying diseases and receiving side effect information were associated with 1.6–2.0 fold increased knowledge of NSAID risks. Conclusion Perceptions and knowledge concerning NSAID risks was generally low in Thai patients, but higher in those who had received side effect information. Risk-related information should be widely provided, especially in high-risk patients

Effect of Resting Patterns of Tamarins (Saguinus fuscicollis and Saguinus mystax) on the Spatial Distribution of Seeds and Seedling Recruitment

The spatial distributions of dispersed seeds have important evolutionary consequences for plants. Repeated defecations in sites frequently used by seed dispersers can result in high seed concentrations. We observed the resting behavior of a mixed-species group of tamarins in Peru and recorded the occurrence of seed dispersal (over 8 mo) and seed fate (over 11–22 mo) to determine whether the location and use of resting sites influenced the spatial distribution of dispersed seeds and seedlings. The tamarins rested mostly on trees (Saguinus fuscicollis: 60.6%, S. mystax: 89.2%) and dead trunks (S. fuscicollis: 24.4%) and used 61% of their resting sites repeatedly. During both the dry and wet seasons, tamarins dispersed significantly more seeds within resting areas (0.00662 and 0.00424 seeds/m2, respectively) than outside them (0.00141 and 0.00181 seeds/m2). Seed survival and seedling recruitment did not differ significantly between resting and other areas, resulting in a higher seedling concentration around the resting sites. Seed density did not increase with the duration or the frequency of use of the resting sites but did increase when we pooled the seasonal resting sites together in 50 m × 50 m quadrats, ultimately causing a clumped distribution of dispersed seeds. The use of resting sites in secondary forest, particularly during the dry season, allows the creation of seedling recruitment centers for species coming from the primary forest. Our findings show that tamarin resting behavior affects the spatial distribution of dispersed seeds and seedlings, and their resting sites play an important role in plant diversity maintenance and facilitate forest regeneration in degraded areas

A Gammaherpesviral Internal Repeat Contributes to Latency Amplification

BACKGROUND: Gammaherpesviruses cause important infections of humans, in particular in immunocompromised patients. The genomes of gammaherpesviruses contain variable numbers of internal repeats whose precise role for in vivo pathogenesis is not well understood. METHODOLOGY/PRINCIPAL FINDINGS: We used infection of laboratory mice with murine gammaherpesvirus 68 (MHV-68) to explore the biological role of the 40 bp internal repeat of MHV-68. We constructed several mutant viruses partially or completely lacking this repeat. Both in vitro and in vivo, the loss of the repeat did not substantially affect lytic replication of the mutant viruses. However, the extent of splenomegaly, which is associated with the establishment of latency, and the number of ex vivo reactivating and genome positive splenocytes were reduced. Since the 40 bp repeat is part of the hypothetical open reading frame (ORF) M6, it might function as part of M6 or as an independent structure. To differentiate between these two possibilities, we constructed an N-terminal M6STOP mutant, leaving the repeat structure intact but rendering ORF M6 unfunctional. Disruption of ORF M6 did neither affect lytic nor latent infection. In contrast to the situation in lytically infected NIH3T3 cells, the expression of the latency-associated genes K3 and ORF72 was reduced in the latently infected murine B cell line Ag8 in the absence of the 40 bp repeat. CONCLUSIONS/SIGNIFICANCE: These data suggest that the 40 bp repeat contributes to latency amplification and might be involved in the regulation of viral gene expression