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Supraglacial lakes and rivers dominate the storage and transport of meltwater on the southwest Greenland Ice Sheet (GrIS) surface. Despite functioning as interconnected hydrologic networks, supraglacial lakes and rivers are commonly studied as independent features, resulting in an incomplete understanding of their collective impact on meltwater storage and routing. We use Landsat 8 satellite imagery to assess the seasonal evolution of supraglacial lakes and rivers on the southwest GrIS during the 2015 melt season. Remotely sensed meltwater areas and volumes are compared with surface runoff simulations from three climate models (MERRA-2, MAR 3.6 and RACMO 2.3), and with in situ observations of proglacial discharge in the Watson River. We find: (1) at elevations >1600 m, 21% of supraglacial lakes and 28% of supraglacial rivers drain into moulins, signifying the presence of high-elevation surface-to-bed meltwater connections even during a colder-than-average melt season; (2) while supraglacial lakes dominate instantaneous surface meltwater storage, supraglacial rivers dominate total surface meltwater area and discharge; (3) the combined surface area of supraglacial lakes and rivers is strongly correlated with modeled surface runoff; and (4) of the three models examined here, MERRA-2 runoff yields the highest overall correlation with observed proglacial discharge in the Watson River.
Interpersonal processes influence our physiological states and associated affect. Physiological arousal dysregulation, a core feature of anxiety disorders, has been identified in children of parents with elevated anxiety. However, little is understood about how parent–infant interpersonal regulatory processes differ when the dyad includes a more anxious parent.
We investigated moment-to-moment fluctuations in arousal within parent-infant dyads using miniaturised microphones and autonomic monitors. We continually recorded arousal and vocalisations in infants and parents in naturalistic home settings across day-long data segments.
Our results indicated that physiological synchrony across the day was stronger in dyads including more rather than less anxious mothers. Across the whole recording epoch, less anxious mothers showed responsivity that was limited to ‘peak’ moments in their child's arousal. In contrast, more anxious mothers showed greater reactivity to small-scale fluctuations. Less anxious mothers also showed behaviours akin to ‘stress buffering’ – downregulating their arousal when the overall arousal level of the dyad was high. These behaviours were absent in more anxious mothers.
Our findings have implications for understanding the differential processes of physiological co-regulation in partnerships where a partner is anxious, and for the use of this understanding in informing intervention strategies for dyads needing support for elevated levels of anxiety.
Gravitational waves from coalescing neutron stars encode information about nuclear matter at extreme densities, inaccessible by laboratory experiments. The late inspiral is influenced by the presence of tides, which depend on the neutron star equation of state. Neutron star mergers are expected to often produce rapidly rotating remnant neutron stars that emit gravitational waves. These will provide clues to the extremely hot post-merger environment. This signature of nuclear matter in gravitational waves contains most information in the 2–4 kHz frequency band, which is outside of the most sensitive band of current detectors. We present the design concept and science case for a Neutron Star Extreme Matter Observatory (NEMO): a gravitational-wave interferometer optimised to study nuclear physics with merging neutron stars. The concept uses high-circulating laser power, quantum squeezing, and a detector topology specifically designed to achieve the high-frequency sensitivity necessary to probe nuclear matter using gravitational waves. Above 1 kHz, the proposed strain sensitivity is comparable to full third-generation detectors at a fraction of the cost. Such sensitivity changes expected event rates for detection of post-merger remnants from approximately one per few decades with two A+ detectors to a few per year and potentially allow for the first gravitational-wave observations of supernovae, isolated neutron stars, and other exotica.
Why patients with psychosis use cannabis remains debated. The self-medication hypothesis has received some support but other evidence points towards an alleviation of dysphoria model. This study investigated the reasons for cannabis use in first-episode psychosis (FEP) and whether strength in their endorsement changed over time.
FEP inpatients and outpatients at the South London and Maudsley, Oxleas and Sussex NHS Trusts UK, who used cannabis, rated their motives at baseline (n = 69), 3 months (n = 29) and 12 months (n = 36). A random intercept model was used to test the change in strength of endorsement over the 12 months. Paired-sample t-tests assessed the differences in mean scores between the five subscales on the Reasons for Use Scale (enhancement, social motive, coping with unpleasant affect, conformity and acceptance and relief of positive symptoms and side effects), at each time-point.
Time had a significant effect on scores when controlling for reason; average scores on each subscale were higher at baseline than at 3 months and 12 months. At each time-point, patients endorsed ‘enhancement’ followed by ‘coping with unpleasant affect’ and ‘social motive’ more highly for their cannabis use than any other reason. ‘Conformity and acceptance’ followed closely. ‘Relief of positive symptoms and side effects’ was the least endorsed motive.
Patients endorsed their reasons for use at 3 months and 12 months less strongly than at baseline. Little support for the self-medication or alleviation of dysphoria models was found. Rather, patients rated ‘enhancement’ most highly for their cannabis use.
Rules of thumb (RoTs) are proposed as a means of promoting higher levels of Defined Contribution (DC) pension saving and to help stimulate debate about the high and uncertain cost of pension provision, leading to the development of solutions. The Lifetime Pension Contribution (LPC) tells young people what pension contribution is required over a full working life to achieve a decent retirement income, calculated as 23% of average UK earnings. Another RoT is that each 1% of earnings provides a pension of 1.5% of earnings. Other RoTs show how costs vary by retirement age and if the saverʼs retirement planning is on track. The current high cost of pensions is partly due to low interest rates and the inefficiencies of the DC market, with inadequate bulk purchasing power and risk sharing. RoTs might help encourage higher employer contributions, either through automatic enrolment or on a voluntary basis.
Effective management of uncertainty can lead to better, more informed decisions. However, many decision makers and their advisers do not always face up to uncertainty, in part because there is little constructive guidance or tools available to help. This paper outlines six Uncertainty Principles to manage uncertainty.
Face up to uncertainty
Deconstruct the problem
Don’t be fooled (un/intentional biases)
Models can be helpful, but also dangerous
Think about adaptability and resilience
Bring people with you
These were arrived at following extensive discussions and literature reviews over a 5-year period. While this is an important topic for actuaries, the intended audience is any decision maker or advisor in any sector (public or private).
Meal timing may influence food choices, neurobiology and psychological states. Our exploratory study examined if time-of-day eating patterns were associated with mood disorders among adults.
During 2004–2006 (age 26–36 years) and 2009–2011 (follow-up, age 31–41 years), N = 1304 participants reported 24-h food and beverage intake. Time-of-day eating patterns were derived by principal components analysis. At follow-up, the Composite International Diagnostic Interview measured lifetime mood disorder. Log binomial and adjacent categories log-link regression were used to examine bidirectional associations between eating patterns and mood disorder. Covariates included sex, age, marital status, social support, education, work schedule, body mass index and smoking.
Three patterns were derived at each time-point: Grazing (intake spread across the day), Traditional (highest intakes reflected breakfast, lunch and dinner), and Late (skipped/delayed breakfast with higher evening intakes). Compared to those in the lowest third of the respective pattern at baseline and follow-up, during the 5-year follow-up, those in the highest third of the Late pattern at both time-points had a higher prevalence of mood disorder [prevalence ratio (PR) = 2.04; 95% confidence interval (CI) 1.20–3.48], and those in the highest third of the Traditional pattern at both time-points had a lower prevalence of first onset mood disorder (PR = 0.31; 95% CI 0.11–0.87). Participants who experienced a mood disorder during follow-up had a 1.07 higher relative risk of being in a higher Late pattern score category at follow-up than those without mood disorder (95% CI 1.00–1.14).
Non-traditional eating patterns, particularly skipped or delayed breakfast, may be associated with mood disorders.
Item 9 of the Patient Health Questionnaire-9 (PHQ-9) queries about thoughts of death and self-harm, but not suicidality. Although it is sometimes used to assess suicide risk, most positive responses are not associated with suicidality. The PHQ-8, which omits Item 9, is thus increasingly used in research. We assessed equivalency of total score correlations and the diagnostic accuracy to detect major depression of the PHQ-8 and PHQ-9.
We conducted an individual patient data meta-analysis. We fit bivariate random-effects models to assess diagnostic accuracy.
16 742 participants (2097 major depression cases) from 54 studies were included. The correlation between PHQ-8 and PHQ-9 scores was 0.996 (95% confidence interval 0.996 to 0.996). The standard cutoff score of 10 for the PHQ-9 maximized sensitivity + specificity for the PHQ-8 among studies that used a semi-structured diagnostic interview reference standard (N = 27). At cutoff 10, the PHQ-8 was less sensitive by 0.02 (−0.06 to 0.00) and more specific by 0.01 (0.00 to 0.01) among those studies (N = 27), with similar results for studies that used other types of interviews (N = 27). For all 54 primary studies combined, across all cutoffs, the PHQ-8 was less sensitive than the PHQ-9 by 0.00 to 0.05 (0.03 at cutoff 10), and specificity was within 0.01 for all cutoffs (0.00 to 0.01).
PHQ-8 and PHQ-9 total scores were similar. Sensitivity may be minimally reduced with the PHQ-8, but specificity is similar.
Influenza and respiratory syncytial virus (RSV) are common causes of respiratory tract infections and place a burden on health services each winter. Systems to describe the timing and intensity of such activity will improve the public health response and deployment of interventions to these pressures. Here we develop early warning and activity intensity thresholds for monitoring influenza and RSV using two novel data sources: general practitioner out-of-hours consultations (GP OOH) and telehealth calls (NHS 111). Moving Epidemic Method (MEM) thresholds were developed for winter 2017–2018. The NHS 111 cold/flu threshold was breached several weeks in advance of other systems. The NHS 111 RSV epidemic threshold was breached in week 41, in advance of RSV laboratory reporting. Combining the use of MEM thresholds with daily monitoring of NHS 111 and GP OOH syndromic surveillance systems provides the potential to alert to threshold breaches in real-time. An advantage of using thresholds across different health systems is the ability to capture a range of healthcare-seeking behaviour, which may reflect differences in disease severity. This study also provides a quantifiable measure of seasonal RSV activity, which contributes to our understanding of RSV activity in advance of the potential introduction of new RSV vaccines.
With the recent discovery of a dozen dusty star-forming galaxies and around 30 quasars at z > 5 that are hyper-luminous in the infrared (μ LIR > 1013 L⊙, where μ is a lensing magnification factor), the possibility has opened up for SPICA, the proposed ESA M5 mid-/far-infrared mission, to extend its spectroscopic studies toward the epoch of reionisation and beyond. In this paper, we examine the feasibility and scientific potential of such observations with SPICA’s far-infrared spectrometer SAFARI, which will probe a spectral range (35–230 μm) that will be unexplored by ALMA and JWST. Our simulations show that SAFARI is capable of delivering good-quality spectra for hyper-luminous infrared galaxies at z = 5 − 10, allowing us to sample spectral features in the rest-frame mid-infrared and to investigate a host of key scientific issues, such as the relative importance of star formation versus AGN, the hardness of the radiation field, the level of chemical enrichment, and the properties of the molecular gas. From a broader perspective, SAFARI offers the potential to open up a new frontier in the study of the early Universe, providing access to uniquely powerful spectral features for probing first-generation objects, such as the key cooling lines of low-metallicity or metal-free forming galaxies (fine-structure and H2 lines) and emission features of solid compounds freshly synthesised by Population III supernovae. Ultimately, SAFARI’s ability to explore the high-redshift Universe will be determined by the availability of sufficiently bright targets (whether intrinsically luminous or gravitationally lensed). With its launch expected around 2030, SPICA is ideally positioned to take full advantage of upcoming wide-field surveys such as LSST, SKA, Euclid, and WFIRST, which are likely to provide extraordinary targets for SAFARI.
Breakthrough Listen is a 10-yr initiative to search for signatures of technologies created by extraterrestrial civilisations at radio and optical wavelengths. Here, we detail the digital data recording system deployed for Breakthrough Listen observations at the 64-m aperture CSIRO Parkes Telescope in New South Wales, Australia. The recording system currently implements two modes: a dual-polarisation, 1.125-GHz bandwidth mode for single-beam observations, and a 26-input, 308-MHz bandwidth mode for the 21-cm multibeam receiver. The system is also designed to support a 3-GHz single-beam mode for the forthcoming Parkes ultra-wideband feed. In this paper, we present details of the system architecture, provide an overview of hardware and software, and present initial performance results.
We describe the motivation and design details of the ‘Phase II’ upgrade of the Murchison Widefield Array radio telescope. The expansion doubles to 256 the number of antenna tiles deployed in the array. The new antenna tiles enhance the capabilities of the Murchison Widefield Array in several key science areas. Seventy-two of the new tiles are deployed in a regular configuration near the existing array core. These new tiles enhance the surface brightness sensitivity of the array and will improve the ability of the Murchison Widefield Array to estimate the slope of the Epoch of Reionisation power spectrum by a factor of ∼3.5. The remaining 56 tiles are deployed on long baselines, doubling the maximum baseline of the array and improving the array u, v coverage. The improved imaging capabilities will provide an order of magnitude improvement in the noise floor of Murchison Widefield Array continuum images. The upgrade retains all of the features that have underpinned the Murchison Widefield Array’s success (large field of view, snapshot image quality, and pointing agility) and boosts the scientific potential with enhanced imaging capabilities and by enabling new calibration strategies.
The role that vitamin D plays in pulmonary function remains uncertain. Epidemiological studies reported mixed findings for serum 25-hydroxyvitamin D (25(OH)D)–pulmonary function association. We conducted the largest cross-sectional meta-analysis of the 25(OH)D–pulmonary function association to date, based on nine European ancestry (EA) cohorts (n 22 838) and five African ancestry (AA) cohorts (n 4290) in the Cohorts for Heart and Aging Research in Genomic Epidemiology Consortium. Data were analysed using linear models by cohort and ancestry. Effect modification by smoking status (current/former/never) was tested. Results were combined using fixed-effects meta-analysis. Mean serum 25(OH)D was 68 (sd 29) nmol/l for EA and 49 (sd 21) nmol/l for AA. For each 1 nmol/l higher 25(OH)D, forced expiratory volume in the 1st second (FEV1) was higher by 1·1 ml in EA (95 % CI 0·9, 1·3; P<0·0001) and 1·8 ml (95 % CI 1·1, 2·5; P<0·0001) in AA (Prace difference=0·06), and forced vital capacity (FVC) was higher by 1·3 ml in EA (95 % CI 1·0, 1·6; P<0·0001) and 1·5 ml (95 % CI 0·8, 2·3; P=0·0001) in AA (Prace difference=0·56). Among EA, the 25(OH)D–FVC association was stronger in smokers: per 1 nmol/l higher 25(OH)D, FVC was higher by 1·7 ml (95 % CI 1·1, 2·3) for current smokers and 1·7 ml (95 % CI 1·2, 2·1) for former smokers, compared with 0·8 ml (95 % CI 0·4, 1·2) for never smokers. In summary, the 25(OH)D associations with FEV1 and FVC were positive in both ancestries. In EA, a stronger association was observed for smokers compared with never smokers, which supports the importance of vitamin D in vulnerable populations.
BACKGROUND: IGTS is a rare phenomenon of paradoxical germ cell tumor (GCT) growth during or following treatment despite normalization of tumor markers. We sought to evaluate the frequency, clinical characteristics and outcome of IGTS in patients in 21 North-American and Australian institutions. METHODS: Patients with IGTS diagnosed from 2000-2017 were retrospectively evaluated. RESULTS: Out of 739 GCT diagnoses, IGTS was identified in 33 patients (4.5%). IGTS occurred in 9/191 (4.7%) mixed-malignant GCTs, 4/22 (18.2%) immature teratomas (ITs), 3/472 (0.6%) germinomas/germinomas with mature teratoma, and in 17 secreting non-biopsied tumours. Median age at GCT diagnosis was 10.9 years (range 1.8-19.4). Male gender (84%) and pineal location (88%) predominated. Of 27 patients with elevated markers, median serum AFP and Beta-HCG were 70 ng/mL (range 9.2-932) and 44 IU/L (range 4.2-493), respectively. IGTS occurred at a median time of 2 months (range 0.5-32) from diagnosis, during chemotherapy in 85%, radiation in 3%, and after treatment completion in 12%. Surgical resection was attempted in all, leading to gross total resection in 76%. Most patients (79%) resumed GCT chemotherapy/radiation after surgery. At a median follow-up of 5.3 years (range 0.3-12), all but 2 patients are alive (1 succumbed to progressive disease, 1 to malignant transformation of GCT). CONCLUSION: IGTS occurred in less than 5% of patients with GCT and most commonly after initiation of chemotherapy. IGTS was more common in patients with IT-only on biopsy than with mixed-malignant GCT. Surgical resection is a principal treatment modality. Survival outcomes for patients who developed IGTS are favourable.
Extensively drug-resistant (XDR) tuberculosis (TB) poses a threat to public health due to its complicated, expensive and often unsuccessful treatment. A cluster of three XDR TB cases was detected among foreign medical students of a Romanian university. The contact investigations included tuberculin skin testing or interferon gamma release assay, chest X-ray, sputum smear microscopy, culture, drug susceptibility testing, genotyping and whole-genome sequencing (WGS), and were addressed to students, personnel of the university, family members or other close contacts of the cases. These investigations increased the total number of cases to seven. All confirmed cases shared a very similar WGS profile. Two more cases were epidemiologically linked, but no laboratory confirmation exists. Despite all the efforts done, the source of the outbreak was not identified, but the transmission was controlled. The investigation was conducted by a team including epidemiologists and microbiologists from five countries (Finland, Israel, Romania, Sweden and the UK) and from the European Centre for Disease Prevention and Control. Our report shows how countries can collaborate to control the spread of XDR TB by exchanging information about cases and their contacts to enable identification of additional cases and transmission and to perform the source investigation.
Different diagnostic interviews are used as reference standards for major depression classification in research. Semi-structured interviews involve clinical judgement, whereas fully structured interviews are completely scripted. The Mini International Neuropsychiatric Interview (MINI), a brief fully structured interview, is also sometimes used. It is not known whether interview method is associated with probability of major depression classification.
To evaluate the association between interview method and odds of major depression classification, controlling for depressive symptom scores and participant characteristics.
Data collected for an individual participant data meta-analysis of Patient Health Questionnaire-9 (PHQ-9) diagnostic accuracy were analysed and binomial generalised linear mixed models were fit.
A total of 17 158 participants (2287 with major depression) from 57 primary studies were analysed. Among fully structured interviews, odds of major depression were higher for the MINI compared with the Composite International Diagnostic Interview (CIDI) (odds ratio (OR) = 2.10; 95% CI = 1.15–3.87). Compared with semi-structured interviews, fully structured interviews (MINI excluded) were non-significantly more likely to classify participants with low-level depressive symptoms (PHQ-9 scores ≤6) as having major depression (OR = 3.13; 95% CI = 0.98–10.00), similarly likely for moderate-level symptoms (PHQ-9 scores 7–15) (OR = 0.96; 95% CI = 0.56–1.66) and significantly less likely for high-level symptoms (PHQ-9 scores ≥16) (OR = 0.50; 95% CI = 0.26–0.97).
The MINI may identify more people as depressed than the CIDI, and semi-structured and fully structured interviews may not be interchangeable methods, but these results should be replicated.
Declaration of interest
Drs Jetté and Patten declare that they received a grant, outside the submitted work, from the Hotchkiss Brain Institute, which was jointly funded by the Institute and Pfizer. Pfizer was the original sponsor of the development of the PHQ-9, which is now in the public domain. Dr Chan is a steering committee member or consultant of Astra Zeneca, Bayer, Lilly, MSD and Pfizer. She has received sponsorships and honorarium for giving lectures and providing consultancy and her affiliated institution has received research grants from these companies. Dr Hegerl declares that within the past 3 years, he was an advisory board member for Lundbeck, Servier and Otsuka Pharma; a consultant for Bayer Pharma; and a speaker for Medice Arzneimittel, Novartis, and Roche Pharma, all outside the submitted work. Dr Inagaki declares that he has received grants from Novartis Pharma, lecture fees from Pfizer, Mochida, Shionogi, Sumitomo Dainippon Pharma, Daiichi-Sankyo, Meiji Seika and Takeda, and royalties from Nippon Hyoron Sha, Nanzando, Seiwa Shoten, Igaku-shoin and Technomics, all outside of the submitted work. Dr Yamada reports personal fees from Meiji Seika Pharma Co., Ltd., MSD K.K., Asahi Kasei Pharma Corporation, Seishin Shobo, Seiwa Shoten Co., Ltd., Igaku-shoin Ltd., Chugai Igakusha and Sentan Igakusha, all outside the submitted work. All other authors declare no competing interests. No funder had any role in the design and conduct of the study; collection, management, analysis and interpretation of the data; preparation, review or approval of the manuscript; and decision to submit the manuscript for publication.
Simulation models are used widely in pharmacology, epidemiology and health economics (HEs). However, there have been no attempts to incorporate models from these disciplines into a single integrated model. Accordingly, we explored this linkage to evaluate the epidemiological and economic impact of oseltamivir dose optimisation in supporting pandemic influenza planning in the USA. An HE decision analytic model was linked to a pharmacokinetic/pharmacodynamics (PK/PD) – dynamic transmission model simulating the impact of pandemic influenza with low virulence and low transmissibility and, high virulence and high transmissibility. The cost-utility analysis was from the payer and societal perspectives, comparing oseltamivir 75 and 150 mg twice daily (BID) to no treatment over a 1-year time horizon. Model parameters were derived from published studies. Outcomes were measured as cost per quality-adjusted life year (QALY) gained. Sensitivity analyses were performed to examine the integrated model's robustness. Under both pandemic scenarios, compared to no treatment, the use of oseltamivir 75 or 150 mg BID led to a significant reduction of influenza episodes and influenza-related deaths, translating to substantial savings of QALYs. Overall drug costs were offset by the reduction of both direct and indirect costs, making these two interventions cost-saving from both perspectives. The results were sensitive to the proportion of inpatient presentation at the emergency visit and patients’ quality of life. Integrating PK/PD–EPI/HE models is achievable. Whilst further refinement of this novel linkage model to more closely mimic the reality is needed, the current study has generated useful insights to support influenza pandemic planning.