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Exercise has been found to be important in maintaining neurocognitive health. However, the effect of exercise intensity level remains relatively underexplored. Thus, to test the hypothesis that self-paced high-intensity exercise and cardiorespiratory fitness (peak aerobic capacity; VO2peak) increase grey matter (GM) volume, we examined the effect of a 6-month exercise intervention on frontal lobe GM regions that support the executive functions in older adults.
Ninety-eight cognitively normal participants (age = 69.06 ± 5.2 years; n = 54 female) were randomised into either a self-paced high- or moderate-intensity cycle-based exercise intervention group, or a no-intervention control group. Participants underwent magnetic resonance imaging and fitness assessment pre-intervention, immediately post-intervention, and 12-months post-intervention.
The intervention was found to increase fitness in the exercise groups, as compared with the control group (F = 9.88, p = <0.001). Changes in pre-to-post-intervention fitness were associated with increased volume in the right frontal lobe (β = 0.29, p = 0.036, r = 0.27), right supplementary motor area (β = 0.30, p = 0.031, r = 0.29), and both right (β = 0.32, p = 0.034, r = 0.30) and left gyrus rectus (β = 0.30, p = 0.037, r = 0.29) for intervention, but not control participants. No differences in volume were observed across groups.
At an aggregate level, six months of self-paced high- or moderate-intensity exercise did not increase frontal GM volume. However, experimentally-induced changes in individual cardiorespiratory fitness was positively associated with frontal GM volume in our sample of older adults. These results provide evidence of individual variability in exercise-induced fitness on brain structure.
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.
To examine the genetic architecture of AAO and PAO and their association with bipolar disorder disease characteristics.
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.
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.
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.
As Ireland confronts the many challenges of broadening the introduction of early intervention services (EIS) for first episode psychosis (FEP) as national policy, this article describes Carepath for Overcoming Psychosis Early (COPE), the EIS of Cavan–Monaghan Mental Health Service, and presents prospective research findings during its first 5 years of operation.
COPE was launched as a rural EIS with an embedded research protocol in early 2012, following an education programme for general practitioners (GPs). Here, operational activities are documented and research findings presented through to late 2016.
During this period, 115 instances of FEP were incepted into COPE, 70.4% via their GP and 29.6% via the Emergency Department. The annual rate of inception was 24.8/100,000 of population aged > 15 years and was 2.1-fold more common among men than women. Mean duration of untreated psychosis was 5.7 months and median time from first psychotic presentation to initiation of antipsychotic treatment was zero days. Assessments of psychopathology, neuropsychology, neurology, premorbid functioning, quality of life, insight, and functionality compared across 10 DSM-IV psychotic diagnoses made at six months following presentation indicated minimal differences between them, other than more prominent negative symptoms in schizophrenia and more prominent mania in bipolar disorder.
COPE illustrates the actuality of introducing and the challenges of operating a rural EIS for FEP. Prospective follow-up studies of the 5-year COPE cohort should inform on the effectiveness of this EIS model in relation to long-term outcome in psychotic illness across what appear to be arbitrary diagnostic boundaries at FEP.
Populations of rigid ryegrass (Lolium rigidum Gaudin) from southern Australia have evolved resistance to the thiocarbamate herbicide prosulfocarb. The inheritance of prosulfocarb resistance was explored by crossing resistant (R) and susceptible (S) individuals. In all families within each cross, except 16.2, the response of the F1 was intermediate between the parents, suggesting that resistance is inherited as a single, partially dominant trait. For 16.2, the response of the F1 was more similar to the S parent, suggesting resistance may be a recessive trait in this population. Segregation at the discriminating dose of 1,200 g ai ha−1 prosulfocarb in population 375-14 fit the ratio (15:1) consistent with two independent dominant alleles; in population 198-15, it fit a ratio (13:3) for two independent alleles, one dominant and one recessive; and in population EP162, it fit a ratio (9:7) for two additive dominant alleles. In contrast, segregation of population 16.2 fit a ratio (7:9) consistent with two independent recessive alleles contributing to prosulfocarb resistance. Four different patterns of resistance to prosulfocarb were identified in different R populations, with inheritance as a dominant allele, dominant and recessive, additive dominant and as an independent recessive allele. This suggests there are several different mechanisms of prosulfocarb resistance present in L. rigidum.
IN GENERAL TEXT BOOKS, Early-medieval Frisia is presented as a rich, long stretched out but in itself coherent, region along the North Sea coast boasting much trading activity. Its landscape between Bruges and Bremen is thought to have been highly maritime, with many local trade settlements having access to the sea. In this paper, we venture to question both its coherency and its maritime character for the period AD 650–850 by adopting a spatial approach. This approach is threefold. First we reconstruct Frisia in the geographical sense. We describe the main types of landscape and define the boundaries of the districts or pagi that together constituted Frisia. Against this background, we then take a look at the supposed trade settlements, to discover that outside the well-known emporia in border positions along major rivers and coasts, no such ever existed. Up to the tenth century, trade transactions that fed the day-to-day economy apparently did not need permanent separate trade centres. This absence of a real hierarchy of settlements strongly suggests that Frisia in its early days was a rural society building its welfare on agricultural production. Our third objective is to get some grip on the political coherency of the Frisian lands and their population groups in the seventh and early eighth century. We do so by focusing on the conditions for the development of large landownership, which are found to have been more favourable in the sandy coastal area of the later Holland than in the clay or terpen districts east of the Vlie. This then gives at the end room to develop a few thoughts on the possible West Frisian or ‘Holland’ power base of the heathen Frisian king Radbod (Redbad) and his predecessor, Aldgisl.
Early-medieval Frisia and the phenomenon of Early-medieval Frisian trade are often mentioned in the same breath. What they have to do with each other, however, is not easy to determine and it is therefore no wonder that this relationship has been under discussion for a long time. In research on Anglo-Saxon England, the literature shows that it is not problematic to speak of visiting traders. For the Frisian regions this seems somewhat more difficult, precisely because the trade is known as ‘Frisian’.
There is growing evidence for human use of geophytes long before the advent of agriculture. Rich in carbohydrates, geophytes were important in many coastal areas where protein-rich marine foods are abundant. On California's Channel Islands, scholars have long questioned how maritime peoples sustained themselves for millennia with limited plant resources. Recent research demonstrates that geophytes were heavily used on the islands for 10,000 years, and here we describe geophyte and other archaeobotanical remains from an approximately 11,500-year-old site on Santa Rosa Island. Currently the earliest evidence for geophyte consumption in North America, our data extend geophyte use on the Channel Islands by roughly 1,500 years and document a diverse and balanced economy for early Paleocoastal peoples. Experimental return rates for a key island geophyte support archaeological evidence that the corms of blue dicks (Dipterostemon capitatus) were a high-ranked staple resource throughout the Holocene.
Three resistant (R) rigid ryegrass (Lolium rigidum Gaudin) populations from southern Australia (EP162, 375-14, and 198-15) with cross-resistance to thiocarbamate, chloroacetamide, and sulfonylisoxazoline herbicides displayed reduced sensitivity to the isoxazolidinone herbicides bixlozone and clomazone. Each of these R populations was exposed to two cycles of recurrent selection (RS) in which plants were treated with the field rate of bixlozone, survivors were bulk crossed, and seed was collected. After the first cycle of recurrent selection (RS1), the LD50 to bixlozone in population 198-15 increased to 17.5-fold compared with the S population and increased further to 26.9-fold after a second cycle of recurrent selection (RS2). The recurrent selection process also increased the level of resistance to bixlozone in populations EP162 and 375-14 (7.8- to 18.4-fold) compared with the S population. Phorate antagonized bixlozone and clomazone in SLR4 (34.6- and 28.1-fold increase in LD50) and both herbicides in populations EP162 (36.5- to 46.6-fold), 375-14 (71.4- to 73.9-fold), and 198-15 (86.4- to 91.5-fold) compared with the absence of phorate. The increase in LD50 of all L. rigidum RS populations when treated with phorate suggests a lack of herbicide activation is not the likely resistance mechanism to these herbicides. This research highlights the elevated risk of thiocarbamate-resistant L. rigidum populations to rapidly evolve resistance to the isoxazolidinone herbicides bixlozone and clomazone.
In March 2020, the UK government ordered mental health services to free up bed space to help manage the COVID-19 pandemic. This meant service users detained under the Mental Health Act were discharged at a higher rate than normal. We analysed whether this decision compromised the safety of this vulnerable group of service users.
We utilised a cohort study design and allocated service users to either the pre-rapid discharge, rapid discharge or post-rapid discharge group. We conducted a recurrent event analysis to assess group differences in the risk of experiencing negative outcomes during the 61 days post-discharge. We defined negative outcomes as crisis service use, re-admission to a psychiatric ward, community incidents of violence or self-harm and death by suicide.
The pre-rapid discharge cohort included 258 service users, the rapid discharge cohort 127 and the post-rapid discharge cohort 76. We found no statistical association between being in the rapid discharge cohort and the risk of experiencing negative outcomes (HR: 1.14, 95% CI: 0.72–1.8, p = 0.58) but a trend towards statistical significance for service users in the post-rapid discharge cohort (HR: 1.61, 95% CI: 0.91–2.83, p = 0.1).
We did not find evidence that service users rapidly discharged from section experienced poorer outcomes. This raises the possibility that the Mental Health Act is applied in an overly restrictive manner, meaning that sections for some formally detained service users could be ended earlier without compromising safety.
The oceans have a huge capability to store, release, and transport heat, water, and various chemical species on timescales from seasons to centuries. Their transports affect global energy, water, and biogeochemical cycles and are crucial elements of Earth’s climate system. Ocean variability, as represented, for example, by sea surface temperature (SST) variations, can result in anomalous diabatic heating or cooling of the overlying atmosphere, which can in turn alter atmospheric circulation in such a way as to feedback on ocean thermal and current structures to modify the original SST variations. Ocean–atmosphere interactions in one ocean basin can also influence remote regions via interbasin teleconnections that can trigger responses having both local and far-field impacts. This chapter highlights the defining aspects of the climate in individual ocean basins, including mean states, seasonal cycles, interannual-to-interdecadal variability, and interactions with other basins. Key components of the global and tropical ocean observing system are also described.
The Zero Suicide framework is a system-wide approach to prevent suicides in health services. It has been implemented worldwide but has a poor evidence-base of effectiveness.
To evaluate the effectiveness of the Zero Suicide framework, implemented in a clinical suicide prevention pathway (SPP) by a large public mental health service in Australia, in reducing repeated suicide attempts after an index attempt.
A total of 604 persons with 737 suicide attempt presentations were identified between 1 July and 31 December 2017. Relative risk for a subsequent suicide attempt within various time periods was calculated using cross-sectional analysis. Subsequently, a 10-year suicide attempt history (2009–2018) for the cohort was used in time-to-recurrent-event analyses.
Placement on the SPP reduced risk for a repeated suicide attempt within 7 days (RR = 0.29; 95% CI 0.11–0.75), 14 days (RR = 0.38; 95% CI 0.18–0.78), 30 days (RR = 0.55; 95% CI 0.33–0.94) and 90 days (RR = 0.62; 95% CI 0.41–0.95). Time-to-recurrent event analysis showed that SPP placement extended time to re-presentation (HR = 0.65; 95% CI 0.57–0.67). A diagnosis of personality disorder (HR = 2.70; 95% CI 2.03–3.58), previous suicide attempt (HR = 1.78; 95% CI 1.46–2.17) and Indigenous status (HR = 1.46; 95% CI 0.98–2.25) increased the hazard for re-presentation, whereas older age decreased it (HR = 0.92; 95% CI 0.86–0.98). The effect of the SPP was similar across all groups, reducing the risk of re-presentation to about 65% of that seen in those not placed on the SPP.
This paper demonstrates a reduction in repeated suicide attempts after an index attempt and a longer time to a subsequent attempt for those receiving multilevel care based on the Zero Suicide framework.
Antibiotic-resistant Gram-negative bacteraemias (GNB) are increasing in incidence. We aimed to investigate the impact of empirical antibiotic therapy on clinical outcomes by carrying out an observational 6-year cohort study of patients at a teaching hospital with community-onset Escherichia coli bacteraemia (ECB), Klebsiella pneumoniae bacteraemia (KPB) and Pseudomonas aeruginosa bacteraemia (PsAB). Antibiotic therapy was considered concordant if the organism was sensitive in vitro and discordant if resistant. We estimated the association between concordant vs. discordant empirical antibiotic therapy on odds of in-hospital death and ICU admission for KPB and ECB. Of 1380 patients, 1103 (79.9%) had ECB, 189 (13.7%) KPB and 88 (6.4%) PsAB. Discordant therapy was not associated with increased odds of either outcome. For ECB, severe illness and non-urinary source were associated with increased odds of both outcomes (OR of in-hospital death for non-urinary source 3.21, 95% CI 1.73–5.97). For KPB, discordant therapy was associated with in-hospital death on univariable but not multivariable analysis. Illness severity was associated with increased odds of both outcomes. These findings suggest broadening of therapy for low-risk patients with community-onset GNB is not warranted. Future research should focus on the relationship between patient outcomes, clinical factors, infection focus and causative organism and resistance profile.
In clinical and translational research, data science is often and fortuitously integrated with data collection. This contrasts to the typical position of data scientists in other settings, where they are isolated from data collectors. Because of this, effective use of data science techniques to resolve translational questions requires innovation in the organization and management of these data.
We propose an operational framework that respects this important difference in how research teams are organized. To maximize the accuracy and speed of the clinical and translational data science enterprise under this framework, we define a set of eight best practices for data management.
In our own work at the University of Rochester, we have strived to utilize these practices in a customized version of the open source LabKey platform for integrated data management and collaboration. We have applied this platform to cohorts that longitudinally track multidomain data from over 3000 subjects.
We argue that this has made analytical datasets more readily available and lowered the bar to interdisciplinary collaboration, enabling a team-based data science that is unique to the clinical and translational setting.
Estimation of RMR using prediction equations is the basis for calculating energy requirements. In the present study, RMR was predicted by Harris–Benedict, Schofield, Henry, Mifflin–St Jeor and Owen equations and measured by indirect calorimetry in 125 healthy adult women of varying BMI (17–44 kg/m2). Agreement between methods was assessed by Bland–Altman analyses and each equation was assessed for accuracy by calculating the percentage of individuals predicted within ± 10 % of measured RMR. Slopes and intercepts of bias as a function of average RMR (mean of predicted and measured RMR) were calculated by regression analyses. Predictors of equation bias were investigated using univariate and multivariate linear regression. At group level, bias (the difference between predicted and measured RMR) was not different from zero only for Mifflin–St Jeor (0 (sd 153) kcal/d (0 (sd 640) kJ/d)) and Henry (8 (sd 163) kcal/d (33 (sd 682) kJ/d)) equations. Mifflin–St Jeor and Henry equations were most accurate at the individual level and predicted RMR within 10 % of measured RMR in 71 and 66 % of participants, respectively. For all equations, limits of agreement were wide, slopes of bias were negative, and intercepts of bias were positive and significantly (P < 0⋅05) different from zero. Increasing age, height and BMI were associated with underestimation of RMR, but collectively these variables explained only 15 % of the variance in estimation bias. Overall accuracy of equations for prediction of RMR is low at the individual level, particularly in women with low and high RMR. The Mifflin–St Jeor equation was the most accurate for this dataset, but prediction errors were still observed in about one-third of participants.
To study the prevalence of social anxiety problem and potential risk factors that may be associated with social anxiety among Malaysian medical undergraduate students.
Social Phobia Inventory (SPIN) and a questionnaire assessing gender, religion, number of siblings, type of previous school and partner status were given to 167 final year medical students at University Malaya.
There were 101 respondents of which 56% of the medical students scored > 19 in the Social Phobia Inventory (SPIN) suggesting that they may be having social anxiety. However, none of the variables analysed were significantly associated with social anxiety.
More than half of the medical students have significant social anxiety symptoms. Students with social anxiety symptoms may find clinical training difficult and this may lead to additional stress and anxiety. This may further decrease academic performance. There is also evidence to suggest that stress during undergraduate training may result in psychological or emotional impairment during professional life and therefore affect the quality of patient care. Furthermore, untreated social anxiety may lead to other complications such as depression and substance abuse. It may also affect their choice of future specialties and prevent them from pursuing what they really want. It is recommended that medical undergraduates be routinely screened for social anxiety in view of its high prevalence, and interventive measures can then be instituted.