We use cookies to distinguish you from other users and to provide you with a better experience on our websites. Close this message to accept cookies or find out how to manage your cookie settings.
To save content items to your account,
please confirm that you agree to abide by our usage policies.
If this is the first time you use this feature, you will be asked to authorise Cambridge Core to connect with your account.
Find out more about saving content to .
To save content items to your Kindle, first ensure coreplatform@cambridge.org
is added to your Approved Personal Document E-mail List under your Personal Document Settings
on the Manage Your Content and Devices page of your Amazon account. Then enter the ‘name’ part
of your Kindle email address below.
Find out more about saving to your Kindle.
Note you can select to save to either the @free.kindle.com or @kindle.com variations.
‘@free.kindle.com’ emails are free but can only be saved to your device when it is connected to wi-fi.
‘@kindle.com’ emails can be delivered even when you are not connected to wi-fi, but note that service fees apply.
Supraglacial debris cover regulates the melt rates of many glaciers in mountainous regions around the world, thereby modifying the availability and quality of downstream water resources. However, the influence of supraglacial debris is often poorly represented within glaciological models, due to the absence of a technique to provide high-precision, spatially continuous measurements of debris thickness. Here, we use high-resolution UAV-derived thermal imagery, in conjunction with local meteorological data, visible UAV imagery and vertically profiled debris temperature time series, to model the spatially distributed debris thickness across a portion of Llaca Glacier in the Cordillera Blanca of Peru. Based on our results, we simulate daily sub-debris melt rates over a 3-month period during 2019. We demonstrate that, by effectively calibrating the radiometric thermal imagery and accounting for temporal and spatial variations in meteorological variables during UAV surveys, thermal UAV data can be used to more precisely represent the highly heterogeneous patterns of debris thickness and sub-debris melt on debris-covered glaciers. Additionally, our results indicate a mean sub-debris melt rate nearly three times greater than the mean melt rate simulated from satellite-derived debris thicknesses, emphasising the importance of acquiring further high-precision debris thickness data for the purposes of investigating glacier-scale melt processes, calibrating regional melt models and improving the accuracy of runoff predictions.
Androgen deprivation therapy (ADT) in men with prostate cancer (PCa) is associated with significant side effects. With the transition of PCa from a foudroyant course to a chronic disease, managing these side effects has become increasingly important. There is growing evidence that nutritional changes and physical activity are beneficial in these patients. Here we examine the impact of written patient information on the physical activity and dietary habits of PCa patients receiving ADT and behaviour changes between baseline and 1 year, in the open-label, non-interventional LEAN study. In total, 959 patients with advanced hormone-sensitive PCa requiring ADT with the Leuprorelin Sandoz® implant were included from January 2014 to July 2015 and followed for ≥ 12 months. At the start of the study, urologists received a questionnaire concerning the written information provided to patients regarding their disease, patient advocacy groups, diet and physical activity. Patients received a questionnaire on their dietary habits and physical activity at the start and end of the study. Urologists from 147 study centres and 540 patients responded to the questionnaires. While 69 % of these patients received disease-specific information, only 30 % and 17 % received information regarding nutrition and physical activity, respectively. The majority of urologists estimate that their patients rarely or never follow guidance on nutrition or physical activity, yet > 90 % of patients indicate they would make use of this information, if provided. Few patients showed behavioural changes between baseline and 1 year without evident differences between patients that received information and those that did not.
The appearance of Beaker pottery in Britain and Ireland during the twenty-fifth century bc marks a significant archaeological horizon, being synchronous with the first metal artefacts. The adoption of arsenical copper, mostly from Ireland, was followed by that of tin-bronze around 2200 bc. However, whilst the copper mine of Ross Island in Ireland is securely dated to the Early Bronze Age, and further such mines in the UK have been dated to the Early and Middle Bronze Age, the evidence for the exploitation of tin ores, the other key ingredient to make bronze, has remained circumstantial. This article contains the detailed analyses of seven stone artefacts from securely dated contexts, using a combination of surface pXRF and microwear analysis. The results provide strong evidence that the tools were used in cassiterite processing. The combined analysis of these artefacts documents in detail the exploitation of Cornish tin during this early phase of metal use in Britain and Ireland.
The Homa Peninsula has been known to science since 1911, and fossil specimens from the area comprise many type specimens for common African mammalian paleospecies. Here we discuss the fauna and the paleoenvironmental information from the Homa Peninsula. The Homa Peninsula is a 200 km2 area in Homa Bay County, situated on the southern margin of the Winam Gulf of Lake Victoria in Kenya (Figure 29.1). Lake Victoria is estimated to be the third largest lake in the world, with a surface area of 68,900 km2 and a maximum length of approximately 616 km. Although its catchment is extensive, it is relatively shallow compared to any other lake of similar size, with a maximum depth of 84 m. Lake Victoria is located in a depression formed by the western and eastern branches of the East African Rift System (EARS), and is at an average elevation of 1135 m a.s.l. (Database for Hydrological Time Series of Inland Waters, 2017).
Response to lithium in patients with bipolar disorder is associated with clinical and transdiagnostic genetic factors. The predictive combination of these variables might help clinicians better predict which patients will respond to lithium treatment.
Aims
To use a combination of transdiagnostic genetic and clinical factors to predict lithium response in patients with bipolar disorder.
Method
This study utilised genetic and clinical data (n = 1034) collected as part of the International Consortium on Lithium Genetics (ConLi+Gen) project. Polygenic risk scores (PRS) were computed for schizophrenia and major depressive disorder, and then combined with clinical variables using a cross-validated machine-learning regression approach. Unimodal, multimodal and genetically stratified models were trained and validated using ridge, elastic net and random forest regression on 692 patients with bipolar disorder from ten study sites using leave-site-out cross-validation. All models were then tested on an independent test set of 342 patients. The best performing models were then tested in a classification framework.
Results
The best performing linear model explained 5.1% (P = 0.0001) of variance in lithium response and was composed of clinical variables, PRS variables and interaction terms between them. The best performing non-linear model used only clinical variables and explained 8.1% (P = 0.0001) of variance in lithium response. A priori genomic stratification improved non-linear model performance to 13.7% (P = 0.0001) and improved the binary classification of lithium response. This model stratified patients based on their meta-polygenic loadings for major depressive disorder and schizophrenia and was then trained using clinical data.
Conclusions
Using PRS to first stratify patients genetically and then train machine-learning models with clinical predictors led to large improvements in lithium response prediction. When used with other PRS and biological markers in the future this approach may help inform which patients are most likely to respond to lithium treatment.
Studying phenotypic and genetic characteristics of age at onset (AAO) and polarity at onset (PAO) in bipolar disorder can provide new insights into disease pathology and facilitate the development of screening tools.
Aims
To examine the genetic architecture of AAO and PAO and their association with bipolar disorder disease characteristics.
Method
Genome-wide association studies (GWASs) and polygenic score (PGS) analyses of AAO (n = 12 977) and PAO (n = 6773) were conducted in patients with bipolar disorder from 34 cohorts and a replication sample (n = 2237). The association of onset with disease characteristics was investigated in two of these cohorts.
Results
Earlier AAO was associated with a higher probability of psychotic symptoms, suicidality, lower educational attainment, not living together and fewer episodes. Depressive onset correlated with suicidality and manic onset correlated with delusions and manic episodes. Systematic differences in AAO between cohorts and continents of origin were observed. This was also reflected in single-nucleotide variant-based heritability estimates, with higher heritabilities for stricter onset definitions. Increased PGS for autism spectrum disorder (β = −0.34 years, s.e. = 0.08), major depression (β = −0.34 years, s.e. = 0.08), schizophrenia (β = −0.39 years, s.e. = 0.08), and educational attainment (β = −0.31 years, s.e. = 0.08) were associated with an earlier AAO. The AAO GWAS identified one significant locus, but this finding did not replicate. Neither GWAS nor PGS analyses yielded significant associations with PAO.
Conclusions
AAO and PAO are associated with indicators of bipolar disorder severity. Individuals with an earlier onset show an increased polygenic liability for a broad spectrum of psychiatric traits. Systematic differences in AAO across cohorts, continents and phenotype definitions introduce significant heterogeneity, affecting analyses.
The interaction between various wave-like structures in screeching jets is considered via both experimental measurements and linear stability theory. Velocity snapshots of screeching jets are used to produce a reduced-order model of the screech cycle via proper orthogonal decomposition. Streamwise Fourier filtering is then applied to isolate the negative and positive wavenumber components, which for the waves of interest in this jet correspond to upstream- and downstream-travelling waves. A global stability analysis on an experimentally derived base flow is conducted, demonstrating a close match to the results obtained via experiment, indicating that the mechanisms considered here are well represented in a linear framework. In both the global stability analysis and the experimental decomposition, three distinct wave-like structures are evident; these waves are also solutions to the cylindrical vortex-sheet dispersion relation. One of the waves is the well-known downstream-travelling Kelvin–Helmholtz mode. Another is the upstream-travelling guided jet mode that has been a topic of recent discussion by a number of authors. The third component, with positive phase velocity, has not previously been identified in screeching jets. Via a local stability analysis, we provide evidence that this downstream-travelling wave is a duct-like mode similar to that recently identified in high-subsonic jets. We further demonstrate that both of the latter two waves are generated by the interaction between the Kelvin–Helmholtz wavepacket and the shock cells in the flow. Finally, we consider the periodic spatial modulation of the coherent velocity fluctuation evident in screeching jets, and show that this modulation can be at least partially explained by the superposition of the three wave-like structures, in addition to any possible modulation of the Kelvin–Helmholtz wavepacket by the shocks themselves.
Psychiatry is facing major challenges during the current coronavirus disease 2019 (COVID)-19 pandemic. These challenges involve its actual and perceived role within the medical system, in particular how psychiatric hospitals can maintain their core mission of attending to people with mental illness while at the same time providing relief to overstretched general medicine services. Although psychiatric disorders comprise the leading cause of the global burden of disease, mental healthcare has been deemphasised in the wake of the onslaught of the pandemic: to make room for emergency care, psychiatric wards have been downsized, clinics closed, psychiatric support systems discontinued and so on. To deal with this pressing issue, we developed a pandemic contingency plan with the aim to contain, decelerate and, preferably, avoid transmission of COVID-19 and to enable and maintain medical healthcare for patients with mental disorders.
Aims
To describe our plan as an example of how a psychiatric hospital can share in providing acute care in a healthcare system facing an acute and highly infectious pandemic like COVID-19 and at the same time provide support for people with mental illness, with or without a COVID-19 infection.
Method
This was a descriptive study.
Results
The plan was based on the German national pandemic strategy and several legal recommendations and was implemented step by step on the basis of the local COVID-19 situation. In addition, mid- and long-term plans were developed for coping with the aftermath of the pandemic.
Conclusions
The plan enabled the University Hospital to maintain medical healthcare for patients with mental disorders. It has offered the necessary flexibility to adapt its implementation to the first and second waves of the COVID-19 pandemic in Germany. The plan is designed to serve as an easily adaptable blueprint for psychiatric hospitals around the world.
Psychosis, and in particular auditory verbal hallucinations (AVHs), are associated with adversity exposure. However, AVHs also occur in populations with no need for care or distress.
Aims
This study investigated whether adversity exposure would differentiate clinical and healthy voice-hearers within the context of a ‘three-hit’ model of vulnerability and stress exposure.
Methods
Samples of 57 clinical and 45 healthy voice-hearers were compared on the three ‘hits’: familial risk; adversity exposure in childhood and in adolescence/adulthood.
Results
Clinical voice-hearers showed greater familial risk than healthy voice-hearers, with more family members with a history of psychosis, but not with other mental disorders. The two groups did not differ in their exposure to adversity in childhood [sexual and non-sexual, victimisation; discrimination and socio-economic status (SES)]. Contrary to expectations, clinical voice-hearers did not differ from healthy voice-hearers in their exposure to victimisation (sexual/non-sexual) and discrimination in adolescence/adulthood, but reported more cannabis and substance misuse, and lower SES.
Conclusions
The current study found no evidence that clinical and healthy voice-hearers differ in lifetime victimisation exposure, suggesting victimisation may be linked to the emergence of AVHs generally, rather than need-for-care. Familial risk, substance misuse and lower SES may be additional risk factors involved in the emergence of need-for-care and distress.
This research communication addresses the hypothesis that Southeast dairy producers' self-reported bulk tank somatic cell count (BTSCC) was associated with producers' response to three statements (1) ‘a troublesome thing about mastitis is the worries it causes me,’ (2) ‘a troublesome thing about mastitis is that cows suffer,’ and (3) ‘my broad goals include taking good care of my cows and heifers.’ Surveys were mailed to producers in Georgia, Kentucky, Mississippi, North Carolina, South Carolina, Tennessee, and Virginia (29% response rate, N = 596; final analysis N = 574), as part of a larger survey to assess Southeastern dairy producers' opinions related to BTSCC. Surveys contained 34 binomial (n = 9), Likert scale (n = 7), and descriptive (n = 18) statements targeted at producer self-assessment of herd records, management practices, and BTSCC. Statements 1 and 2 were assessed on a 5-point Likert scale from ‘strongly disagree’ to ‘strongly agree.’ Statement 3 was assessed on a 5-point Likert scale from ‘very unimportant’ to ‘very important.’ Reported mean BTSCC for all participants was 254 500 cells/ml. Separate univariable logistic regressions using generalized linear mixed models (SAS 9.4, Cary, NC, USA) with a random effect of farm, were performed to determine if BTSCC was associated with probability for a producer's response to statements. If BTSCC was significant, forward manual addition was performed until no additional variables were significant (P ≤ 0.05), but included BTSCC, regardless of significance. Bulk tank somatic cell count was associated with ‘a troublesome thing about mastitis is the worries it causes me,’ but not with Statements 2 or 3. This demonstrates that >75% of Southeastern dairy producers are concerned with animal care and cow suffering, regardless of BTSCC. Understanding Southeast producers' emphasis on cow care is necessary to create targeted management tools for herds with elevated BTSCC.
Stimulant drugs can cause persistent changes in the brain. Imaging studies show that these changes are most apparent in dopamine transporter (DAT) or receptor availability within the striatum.
Methods:
This work focuses on influences of stimulant use on dopaminergic function assessed using nuclear-medicine imaging (PET/SPECT). Included are 39 studies on 655 cocaine, amphetamine, methamphetamine or nicotine users, as well as 690 healthy controls. Metaanalyses were conducted separately for D2/D3 receptors and dopamine transporters of the entire striatum, its subregions caudate and putamen respectively.
Results:
Meta-analyses results regarding nicotine did not show significant effects between smokers and nonsmokers. In cocaine users there was a significant decrease in dopamine receptor availability in all regions. The striatal DAT availability was significantly increased in cocaine users. Methamphetamine users showed a significantly decreased dopamine receptor and transporter density in all regions. Significant results also indicate a lower transporter availability in all regions. Amphetamine users showed reduced DAT availability in the striatum, as well as in the sub regions.
Conclusion:
This meta-analysis provides evidence that there are ongoing changes in the dopaminergic system associated with the use of stimulants. Especially the results of cocaine, methamphetamine and amphetamine use mainly showed a downregulation. In addition, this meta-analysis is the first to include nicotine. This subset of studies showed evidence for a decreased receptor and DAT availability but no significant results were found in the metaanalyses.
To evaluate how avian influenza virus (AIV) circulates among the avifauna of the Antarctic and sub-Antarctic islands, we surveyed 14 species of birds from Marion, Livingston and Gough islands. A competitive enzyme-linked immunosorbent assay was carried out on the sera of 147 birds. Quantitative reverse transcription polymerase chain reaction was used to detect the AIV genome from 113 oropharyngeal and 122 cloacal swabs from these birds. The overall seroprevalence to AIV infection was 4.8%, with the only positive results coming from brown skuas (Catharacta antarctica) (4 out of 18, 22%) and southern giant petrels (Macronectes giganteus) (3 out of 24, 13%). Avian influenza virus antibodies were detected in birds sampled from Marion and Gough islands, with a higher seroprevalence on Marion Island (P = 0.014) and a risk ratio of 11.29 (95% confidence interval: 1.40–91.28) compared to Gough Island. The AIV genome was not detected in any of the birds sampled. These results confirm that AIV strains are uncommon among Antarctic and sub-Antarctic predatory seabirds, but they may suggest that scavenging seabirds are the main avian reservoirs and spreaders of this virus in the Southern Ocean. Further studies are necessary to determine the precise role of these species in the epidemiology of AIV.
We present a conditional space–time proper orthogonal decomposition (POD) formulation that is tailored to the eduction of the average, rare or intermittent events from an ensemble of realizations of a fluid process. By construction, the resulting spatio-temporal modes are coherent in space and over a predefined finite time horizon, and optimally capture the variance, or energy of the ensemble. For the example of intermittent acoustic radiation from a turbulent jet, we introduce a conditional expectation operator that focuses on the loudest events, as measured by a pressure probe in the far field and contained in the tail of the pressure signal’s probability distribution. Applied to high-fidelity simulation data, the method identifies a statistically significant ‘prototype’, or average acoustic burst event that is tracked over time. Most notably, the burst event can be traced back to its precursor, which opens up the possibility of prediction of an imminent burst. We furthermore investigate the mechanism underlying the prototypical burst event using linear stability theory and find that its structure and evolution are accurately predicted by optimal transient growth theory. The jet-noise problem demonstrates that the conditional space–time POD formulation applies even for systems with probability distributions that are not heavy-tailed, i.e. for systems in which events overlap and occur in rapid succession.
OBJECTIVES/SPECIFIC AIMS: The National HIV/AIDS strategy aims to increase retention in care (RIC) to reduce HIV transmission and mortality. Previous studies have evaluated clinic-level interventions such as appointment reminders and peer navigation. However, few studies have investigated the association between multiple clinic-level factors and RIC among PLWH across the United States. We conducted a multi-site cohort study to identify clinic-level factors associated with RIC in the United States from 2010-2016. METHODS/STUDY POPULATION: We included PLWH with at least one HIV primary care visit from 2010-2016 at seven sites of the Center for AIDS Research (CFAR) Network of Integrated Clinical Systems (CNICS). Individual-level data collected as part of routine clinical care were abstracted from the electronic health record. Clinic-level data were gathered through a survey and included questions on site characteristics (i.e. clinic volume) as well as services available at the site during each year of the study: peer navigation, RIC posters/brochures, laboratory test timing, flexible scheduling, appointment reminder types, and stigma support services defined as intensive HIV education and advocacy regarding support to address stigma at outreach visits. RIC was defined as ≥2 encounters per year, ≥90 days apart, observed until death, administrative censoring (December 31, 2016), or loss to follow-up (no visit for >12 months with no future visits). Poisson panel regression with robust error variance, clustering by site and adjusting for calendar year, age (modeled with a cubic spline), sex, race/ethnicity, and HIV transmission risk factor, was used to estimate incident rate ratios (IRR) with 95% confidence intervals (CI) for RIC. Clustering by site has been shown to absorb for clustering that could occur at the individual level as well. RESULTS/ANTICIPATED RESULTS: Among 21,046 patients contributing 103,348 person-years, 67% of person-years were RIC. Text appointment reminders (IRR = 1.13; 95% CI: 1.03-1.24) and stigma support services (IRR=1.11; 95% CI:1.04-1.19) were significantly associated with RIC. RIC disparities in individual-level patient characteristics were observed even after accounting for clinic-level characteristics. Older patients were more likely to be RIC demonstrated through year comparisons due to the use of a spline; for age 50 years (IRR = 1.07, 95% CI: 1.06-1.08) and 60 years (IRR = 1.15, 95% CI: 1.13-1.17) compared to 45 years. Female PLWH were more likely to be RIC compared to males (IRR = 1.03, 95% CI: 1.02-1.05) and Hispanic PLWH were more likely to be RIC compared to white, non-Hispanic PLWH (IRR = 1.09, 95% CI: 1.05-1.13). Although commonly found to be associated with worse RIC, Black race and injection drug use were not associated with RIC in this population. DISCUSSION/SIGNIFICANCE OF IMPACT: In this multi-site US cohort study from 2010-2016, availability of text appointment reminders and stigma support services at a clinic were associated with approximately 10% higher probability of RIC than at clinics without those services. RIC disparities persisted with respect to individual-level characteristics of age, sex, and race/ethnicity even after accounting for these clinic-level factors. Prospective studies examining the impact of these clinic-level factors and individual-level uptake of these services on RIC are needed.
Motivated by the problem of jet–flap interaction noise, we study the tonal dynamics that occurs when an isothermal turbulent jet grazes a sharp edge. We perform hydrodynamic and acoustic pressure measurements to characterise the tones as a function of Mach number and streamwise edge position. The observed distribution of spectral peaks cannot be explained using the usual edge-tone model, in which resonance is underpinned by coupling between downstream-travelling Kelvin–Helmholtz wavepackets and upstream-travelling sound waves. We show, rather, that the strongest tones are due to coupling between Kelvin–Helmholtz wavepackets and a family of trapped, upstream-travelling acoustic modes in the potential core, recently studied by Towne et al. (J. Fluid Mech. vol. 825, 2017) and Schmidt et al. (J. Fluid Mech. vol. 825, 2017). We also study the band-limited nature of the resonance, showing the high-frequency cutoff to be due to the frequency dependence of the upstream-travelling waves. Specifically, at high Mach number, these modes become evanescent above a certain frequency, whereas at low Mach number they become progressively trapped with increasing frequency, which inhibits their reflection in the nozzle plane.