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Triple chronotherapy (sleep deprivation for 36 h, followed by 4 days of advancing the time of sleep and daily morning bright-light therapy for 6 months) has demonstrated benefits for the rapid treatment of depressive symptoms in four small controlled trials of in-patients.
To test the feasibility of recruitment and delivery of triple chronotherapy for out-patients with depression (ISRCTN17706836; NCT03405493).
In a single-blind trial, 82 participants were randomised to triple chronotherapy or a control intervention. The primary outcome was the number of participants recruited per month and adherence to the protocol. Secondary outcomes included the 6-item Hamilton Rating Scale for Depression (HRSD-6) at 1 week. Timings of observer ratings were baseline and 1, 2, 4, 8 and 26 weeks after randomisation.
The triple chronotherapy group stayed awake for the planned 36 h and 89.9% adhered to the plan of phase advance of their sleep over the following 4 days. We achieved our recruitment target (60 participants completed the trial within 13 months). There were no reported adverse side-effects. We found a significant difference between the groups by intention-to-treat analysis for the HRSD-6 at weeks 1, 8 and 26. There was a large effect size of Cohen's d = 0.8 on HRSD-6 score at week 1, increasing to d = 1.30 at week 26. A response (≥50% reduction in symptoms) was achieved by 33.3% in the triple chronotherapy group and 16.2% in the control group. This stayed relatively steady until week 26 (35.9 v. 13.9%).
Triple chronotherapy produced a significant and rapid benefit after 1 week in out-patients with depression that was sustained at 26 weeks. Cost-effectiveness trials with a larger clinical sample are required.
Seed retention, and ultimately seed shatter, are extremely important for the efficacy of harvest weed seed control (HWSC) and likely influenced by various agro-ecological and environmental factors. Field studies investigated seed shattering phenology of 22 weed species across three soybean [Glycine max (L.) Merr.] producing regions in the US. We further evaluated the potential drivers of seed shatter in terms of weather conditions, growing degree days, and plant biomass. Based on the results, weather conditions had no consistent impact on weed seed shatter. However, there was a positive correlation between individual weed plant biomass and delayed weed-seed shattering rates during harvest. This work demonstrates that HWSC can potentially reduce weed seedbank inputs of plants that have escaped early season management practices and retained seed through harvest. However, smaller individuals of plants within the same population that shatter seed before harvest pose a risk of escaping early season management and HWSC.
The nonlinear dynamics of a two-sided collapsible channel flow is investigated by using an immersed boundary-lattice Boltzmann method. The stability of the hydrodynamic flow and collapsible channel walls is examined over a wide range of Reynolds numbers $Re$, structure-to-fluid mass ratios $M$ and external pressures $P_e$. Based on extensive simulations, we first characterise the chaotic behaviours of the collapsible channel flow and explore possible routes to chaos. We then explore the physical mechanisms responsible for the onset of self-excited oscillations. Nonlinear and rich dynamic behaviours of the collapsible system are discovered. Specifically, the system experiences a supercritical Hopf bifurcation leading to a period-1 limit cycle oscillation. The existence of chaotic behaviours of the collapsible channel walls is confirmed by a positive dominant Lyapunov exponent and a chaotic attractor in the velocity-displacement phase portrait of the mid-point of the collapsible channel wall. Chaos in the system can be reached via period-doubling and quasi-periodic bifurcations. It is also found that symmetry breaking is not a prerequisite for the onset of self-excited oscillations. However, symmetry breaking induced by mass ratio and external pressure may lead to a chaotic state. Unbalanced transmural pressure, wall inertia and shear layer instabilities in the vorticity waves contribute to the onset of self-excited oscillations of the collapsible system. The period-doubling, quasi-periodic and chaotic oscillations are closely associated with vortex pairing and merging of adjacent vortices, and interactions between the vortices on the upper and lower walls downstream of the throat.
Epidemiological and intervention studies have reported negative health effects of sucrose intake, but many of these studies were not representative of typical dietary habits. In this pilot study, we aimed to test the effect of increasing sucrose intakes for 1 week on body composition and blood pressure and explore the feasibility of consuming high intakes of sucrose in addition to a habitual diet. In a randomised crossover design study, twelve healthy participants (50 % female, age 28⋅4 ± 10 years, BMI 25 ± 3 kg/m2), consumed either 40, 80 or 120 g sucrose in 500 ml water in addition to their habitual diet every day for 1 week, with a 1-week washout between treatment periods. Body composition (assessed using bioelectrical impedance) and blood pressure measurements were taken before and after each intervention phase. All participants reported no issues with consuming the sucrose dose for the intervention period. There was a significant increase in systolic blood pressure following 120 g sucrose intake (P = 0⋅006), however there was no significant changes to blood pressure, body weight, BMI, percentage protein, fat or water (P > 0⋅05) when comparing change from baseline values. There was also no effect of sucrose intakes on energy or macronutrient intakes during the intervention (P > 0⋅05). We show here that varying doses of sucrose over a 1-week period have no effect on body composition or blood pressure. The amounts of sucrose used were an acceptable addition to the habitual diet and demonstrate the feasibility of larger-scale studies of chronic sucrose supplementation.
Recommendations for free sugar intake in the UK should be no more than 5 % of total energy due to increased health risks associated with overconsumption. It was therefore of interest to examine free sugar intakes and associations with health parameters in the UK population. The UK National Diet and Nutrition Survey rolling programme (2008–2017) was used for this study. Dietary intake, anthropometrical measurements and clinical biomarker data collated from 5121 adult respondents aged 19–64 years were statistically analysed. Compared with the average total carbohydrate intake (48 % of energy), free sugars comprised 12·5 %, with sucrose 9 % and fructose 3·5 %. Intakes of these sugars, apart from fructose, were significantly different over collection year (P < 0·001) and significantly higher in males (P < 0·001). Comparing those consuming above or below the UK recommendations for free sugars (5 % energy), significant differences were found for BMI (P < 0·001), TAG (P < 0·001), HDL (P = 0·006) and homocysteine concentrations (P = 0·028), and significant sex differences were observed (e.g. lower blood pressure in females). Regression analysis demonstrated that free sugar intake could predict plasma TAG, HDL and homocysteine concentrations (P < 0·0001), consistent with the link between these parameters and CVD. We also found selected unhealthy food choices (using the UK Eatwell Guide) to be significantly higher in those that consumed above the recommendations (P < 0·0001) and were predictors of free sugar intakes (P < 0·0001). We have shown that adult free sugar intakes in the UK population are associated with certain negative health parameters that support the necessary reduction in free sugar intakes for the UK population.
Johannesburg was still a brash mining town, better known for the production of wealth than knowledge, and the University of the Witwatersrand a mere ten years old when, in 1932, these ten lectures were delivered under the auspices of the University Philosophical Society. They portrayed the ideas of the university's leading academics of the day, and the programme of lectures reveals a studied effort to introduce an element of bipartisan political representation between English and Afrikaner in South Africa by including Wits' first principal, Jan Hofmeyr, and politician, D.F. Malan, as discussion chairs. Yet, no black intellectuals were represented and, indeed, the politics of racial segregation bursts through the text only in a few of the contributions. For the most part, race is alluded to only in passing. As Saul Dubow explains in his new introduction to this re-issue of the lectures, Our Changing World-View was an occasion for Wits' leading faculty members to position the young university as a mature institution with a leadership role in public affairs. Above all, it was a means to project the university as a research as well as a teaching institution, led by a vigorous and ambitious cohort of liberal-minded intellectuals. That all were male and white will be immediately apparent to readers of this reissued volume. Ranging from economics, psychology, a spurious rebuttal of evolution to a substantial revisionist history and the perils of the 'machine age', this book is a sombre reflection of intellectual history and the academy's role in promulgating political and social divisions in South Africa.
Background: Identification of hospitalized patients with enteric multidrug-resistant organism (MDRO) carriage, combined with implementation of targeted infection control interventions, may help reduce MDRO transmission. However, the optimal surveillance approach has not been defined. We sought to determine whether daily serial rectal surveillance for MDROs detects more incident cases (acquisition) of MDRO colonization in medical intensive care unit (MICU) patients than admission and discharge surveillance alone. Methods: Prospective longitudinal observational single-center study from January 11, 2017, to January 11, 2018. Inclusion criteria were ≥3 consecutive MICU days and ≥2 rectal or stool swabs per MICU admission. Daily rectal or stool swabs were collected from patients and cultured for MDROs, including vancomycin-resistant Enterococcus (VRE), carbapenem-resistant Enterobacterales (CRE), third-generation cephalosporin-resistant Enterobacterales (3GCR), and extended-spectrum β-lactamase–producing Enterobacterales (ESBL-E) (as a subset of 3GCR). MDRO detection at any time during the MICU stay was used to calculate prevalent colonization. Incident colonization (acquisition) was defined as new detection of an MDRO after at least 1 prior negative swab. We then determined the proportion of prevalent and incident cases detected by daily testing that were also detected when only first swabs (admission) and last swabs (discharge) were tested. Data were analyzed using SAS version 9.4 software. Results: In total, 939 MICU stays of 842 patients were analyzed. Patient characteristics were median age 64 years (interquartile range [IQR], 51–74), median MICU length of stay 5 days (IQR, 3–8), median number of samples per admission 3 (IQR, 2–5), and median Charlson index 4 (IQR, 2–7). Prevalent colonization with any MDRO was detected by daily swabbing in 401 stays (42.7%). Compared to daily serial swabbing, an admission- and discharge-only approach detected ≥86% of MDRO cases (ie, overall prevalent MDRO colonization). Detection of incident MDRO colonization by an admission- or discharge-only approach would have detected fewer cases than daily swabbing (Figure 1); ≥34% of total MDRO acquisitions would have been missed. Conclusions: Testing patients upon admission and discharge to an MICU may fail to detect MDRO acquisition in more than one-third of patients, thereby reducing the effectiveness of MDRO control programs that are targeted against known MDRO carriers. The poor performance of a single discharge swab may be due to intermittent or low-level MDRO shedding, inadequate sampling, or transient MDRO colonization. Additional research is needed to determine the optimal surveillance approach of enteric MDRO carriage.
As Richard Wright was establishing his career in the 1940s, he maintained profitable but uneasy relationships with white audiences, especially those approaching his works within the political liberalism that held sway over much of American culture in this period. While Wright’s works struck a powerful chord in redirecting American culture to acknowledge the costs of race-based exclusion, the extent of that change was only ever partial, and often depended on Wright’s narratives being disseminated and received along the lines of established, white cultural parameters. At the same time, the commercial and critical successes of Native Son and Black Boy established the foundation for Wright’s career, and his interactions with white writers, living and dead, provided influential models and connections. This essay explores this tension while situating Wright’s work and publishing history in relation to civil rights activism and cultural liberalism in the 1940s, and its (sometimes distorted) reflection in the images of Wright circulated by his publishers and the mainstream press, by tracing the paratextual materials attached to Wright’s books and the wide range of publication venues in which his stories and essays appeared.
National surveys show that over 56% of adults in England gamble annually, and of those surveyed, 0.5% were problem gamblers, equating to 300,000 problem gamblers at any point. The prevalence of problem gambling in patients with a substance misuse disorder ranges from 20.5% to 55%.
The audit aims to improve the care of patients with comorbid substance misuse and gambling disorder by assessing the extent to which the service currently enquires about and records problem gambling in its patient cohort.
It is hypothesised that as no formal recording process is in place locally, this information will not be recorded systematically and in a way that is easily retrievable by the service.
The audit will allow the service to assess whether changes need to be made to the initial assessment pathways into treatment for substance-related disorders to adequately record this information so that further assessment and onward referral can take place.
All active patients (n = 2824) within the service had both their electronic initial assessments and their entire electronic notes screened for terms such as ‘betting’ and ‘gambling’ and this was recorded using an Excel spreadsheet. Prevalence rates across the teams (opiates, non-opiates and alcohol) were then calculated.
The results showed that 0% of patients had any entries in their initial screening noting any gambling activity. Further scrutiny of the records revealed that only 3.5% (n-99) had ever discussed gambling with a worker in any of the services.
The majority (n = 52) of patients who had discussed gambling only had one positive search result, suggesting this was not followed-up in a systematic fashion. Recommendations are to revise the common assessment pro-forma to include a validated brief screening tool (lie/bet), where one positive answer triggers a further assessment with an appropriate clinician for consideration of referral to the local NHS gambling service.
Among low- and middle-income countries (LMICs), bipolar disorder is recognized as one of the leading causes of disease burden for adults and is associated with marked suicide risk. There are limited data on suicidal ideation in bipolar disorder from LMICs. This study presents cross-sectional data on the prevalence of suicidality and associated patient characteristics among patients with bipolar depression in Pakistan, a lower-middle income country and the fifth most populous country in the world.
Participants were recruited through outpatient psychiatric clinics in between 2016–2019 in Karachi, Lahore, Hyderabad and Rawalpindi between 2016–2019. Participants were aged 18 to 65 years with a known diagnosis of bipolar disorder and currently in a depressive episode. Suicidality was assessed using the suicide item of the 17-item Hamilton Depression Rating Scale (HAM-D) and levels of severity were categorized as absent, mild/moderate, or severe. Biometric data and biomarkers were obtained. Descriptive statistics were used to describe prevalence and proportional odds regression models were applied to establish correlates to suicidal ideation.
Among the 266 participants, 67% indicated suicidality of any level and 16% endorsed severe suicidality. Lower body mass index (BMI) (OR = 0.93, 95% CI = 0.88–0.98), higher HAM-D score (OR = 1.29, 95% CI = 1.16–1.43), lower C-reactive protein (CRP) level (OR = 0.53, 95% CI = 0.40–0.70), and increased number of inpatient hospitalizations (OR = 1.16, 95% CI = 1.03–1.31) were identified as significant predictors of suicidality in the fully adjusted regression model. No patient demographic data, including age, gender, marital status, socioeconomic status, and years of education were associated with severity of suicidality.
There exists a high prevalence of suicidal ideation among patients with bipolar depression in Pakistan. Our findings add to the limited literature on suicidality in bipolar disorder in the LMIC context and suggest roles of biological variables such as BMI and CRP level in predicting suicidal ideation and potentially suicidal behaviours in bipolar depression. More studies are needed to see whether such findings can be replicated in other similar LMIC settings, and to explore potential physiological pathways linking BMI, inflammatory biomarkers and suicidality in bipolar disorder.
Triple chronotherapy (defined as sleep deprivation for 36 hours, followed by 4 days of advancing the time of sleep, together with daily morning bright light therapy for 6 months) has demonstrated benefits for the rapid treatment of depressive symptoms in 4 small, controlled trials of in-patients. Our aims were to test the feasibility of recruitment and delivery of triple chronotherapy for out-patients with depression.
In a single blind trial, 82 participants were randomised to either triple chronotherapy or a control intervention. The primary outcome was Hamilton Depression Rating Scale 6 item (HAM-D6) at 1 week. Timings of observer ratings were baseline; 1 week; 2 weeks; 4 weeks; 8 weeks and 26 weeks after randomisation. Triple chronotherapy consisted of (a) Total sleep deprivation for 36 hours. On Day 1 patients were supported in a small group to stay awake at night with an occupational therapist, (b) Phase Advance of Sleep over 4 days. Phase Advance began after the first night of sleep deprivation, when they left the hospital at about 8am and were asked to go to bed earlier at about 5pm and rise at about 1am. Their sleep and wake up times were then shifted 2 hours later on each of the following three days until they attained their usual bedtime again at about 11pm.As a control for the triple chronotherapy, participants were given psychoeducation and written information on sleep hygiene. They were also given SomniLight amber light daily for 1 week in the morning.
Participants in the triple chronotherapy group were able to stay awake for the planned thirty-six hours and 89.9% adhered to the plan of phase advance of their sleep over the following 4 days. We achieved our recruitment target with 60 participants having completed the trial within 13 months. There were no reported adverse side effects. We explored outcomes and found a significant difference between the groups for the HAM-D6 at week 1, 8 and 26. Response (> 50% reduction in symptoms) was achieved by 52% in the triple chronotherapy group compared to 18% in the control group at week 1. This gradually increased to 70% achieving response in the triple chronotherapy group at week 26 compared to 22% in the control group.
Triple chronotherapy produced a significant and rapid benefit after 1 week in out-patients with depression that was sustained at 26 weeks. Further cost-effective trials with a larger clinical sample size are required.
Individuals with treatment-resistant depression (TRD) experience a high burden of illness. Current guidelines recommend a stepped care approach for treating depression, but the extent to which best-practice care pathways are adhered to is unclear.
To explore the extent and nature of ‘treatment gaps’ (non-adherence to stepped care pathways) experienced by a sample of patients with established TRD (non-response to two or more adequate treatments in the current depressive episode) across three cities in the UK.
Five treatment gaps were considered and compared with guidelines, in a cross-sectional retrospective analysis: delay to receiving treatment, lack of access to psychological therapies, delays to medication changes, delays to adjunctive (pharmacological augmentation) treatment and lack of access to secondary care. We additionally explored participant characteristics associated with the extent of treatment gaps experienced.
Of 178 patients with TRD, 47% had been in the current depressive episode for >1 year before initiating antidepressants; 53% had received adequate psychological therapy. A total of 47 and 51% had remained on an unsuccessful first and second antidepressant trial respectively for >16 weeks, and 24 and 27% for >1 year before medication switch, respectively. Further, 54% had tried three or more antidepressant medications within their episode, and only 11% had received adjunctive treatment.
There appears to be a considerable difference between treatment guidelines for depression and the reality of care received by people with TRD. Future research examining representative samples of patients could determine recommendations for optimising care pathways, and ultimately outcomes, for individuals with this illness.
Potential effectiveness of harvest weed seed control (HWSC) systems depends upon seed shatter of the target weed species at crop maturity, enabling its collection and processing at crop harvest. However, seed retention likely is influenced by agroecological and environmental factors. In 2016 and 2017, we assessed seed-shatter phenology in 13 economically important broadleaf weed species in soybean [Glycine max (L.) Merr.] from crop physiological maturity to 4 wk after physiological maturity at multiple sites spread across 14 states in the southern, northern, and mid-Atlantic United States. Greater proportions of seeds were retained by weeds in southern latitudes and shatter rate increased at northern latitudes. Amaranthus spp. seed shatter was low (0% to 2%), whereas shatter varied widely in common ragweed (Ambrosia artemisiifolia L.) (2% to 90%) over the weeks following soybean physiological maturity. Overall, the broadleaf species studied shattered less than 10% of their seeds by soybean harvest. Our results suggest that some of the broadleaf species with greater seed retention rates in the weeks following soybean physiological maturity may be good candidates for HWSC.
Seed shatter is an important weediness trait on which the efficacy of harvest weed seed control (HWSC) depends. The level of seed shatter in a species is likely influenced by agroecological and environmental factors. In 2016 and 2017, we assessed seed shatter of eight economically important grass weed species in soybean [Glycine max (L.) Merr.] from crop physiological maturity to 4 wk after maturity at multiple sites spread across 11 states in the southern, northern, and mid-Atlantic United States. From soybean maturity to 4 wk after maturity, cumulative percent seed shatter was lowest in the southern U.S. regions and increased moving north through the states. At soybean maturity, the percent of seed shatter ranged from 1% to 70%. That range had shifted to 5% to 100% (mean: 42%) by 25 d after soybean maturity. There were considerable differences in seed-shatter onset and rate of progression between sites and years in some species that could impact their susceptibility to HWSC. Our results suggest that many summer annual grass species are likely not ideal candidates for HWSC, although HWSC could substantially reduce their seed output during certain years.
Antimicrobials are used on dairy farms for preventing disease and treating common infections such as mastitis. Objective: We aimed to understand farmworker practices that potentially contribute to transmission of antimicrobial resistance bacteria and their genes (ARG) among animals and farm workers, and to identify human behavioral interventions to reduce risk. Methods: Focus groups with farm workers were held at 8 dairy farms across Wisconsin selected to represent a range of antibiotic use in cattle. We explored the nature of potentially high-risk practices and farm-worker knowledge and experiences with antibiotic use and resistance. Farm workers were asked to describe common tasks, including hand hygiene and eating practices, and the policies guiding these practices. Focus groups were conducted in English and Spanish guided by the Systems Engineering in Patient Safety (SEIPS) framework, adapted for an agricultural context. Discussions were recorded, transcribed, and translated. A content analysis was conducted to identify themes. Dedoose version 8.0.35 software was used to organize the data. Results: In total, 10 focus groups were conducted on 8 farms. Knowledge of when to use antibiotics for human health varied; upset stomach, headache, and flu symptoms were suggested as appropriate uses. Few workers had personal experience with antibiotic resistance at home or on the farm. Some displayed knowledge of the role of antibiotic stewardship in preventing the spread of ARG (“I guess all dairy farmers have a responsibility not to overdo it”). Others associated the risk of spread with the consumption of raw milk or meat from cows receiving antibiotics. Knowledge of personal protective equipment was stronger among workers who commonly reported glove use. Some perceived glove use to be mandatory, and others chose to wear gloves in the perceived absence of written rules. Some workers reported changing gloves numerous times throughout the day, and others did so less frequently or “only when they rip.” In general, hand hygiene practices are guided by individual knowledge of established rules, beliefs about risk, and personal discretion. Conclusions: Knowledge about mechanisms of spread of ARGs varies among workers on Wisconsin dairy farms and reflects a combination of farm-level rules, experience, individual knowledge, and beliefs. Applying knowledge from the healthcare setting to reduce ARG spread into agriculture is crucial to the tenets of One Health. Programs to reduce ARG spread on dairy farms should focus on proper hand hygiene and PPE use at the level of knowledge, beliefs, and practices.
Funding: Funding: was provided by the USDA-NIFA Food Safety Challenge (grant no. 2017-68003-26500).
A control volume based analytical method for calculating the efficiency $\eta$ of flapping foil power generators was developed for single and tandem foil configurations. Ignoring unsteady effects and non-uniform pressures resulted in theoretical limits identical to the Betz ($\eta =16/27$ for a single turbine) and Newman ($\eta =16/25$ for tandem turbines) limits. Inclusion of unsteady flow and non-uniform pressure distributions produced theoretical efficiency maxima in excess of these limits. Simulation of single and tandem foil cases to determine the magnitude of these effects showed that the Betz limit would not be exceeded by a single foil system in practice, but that it is conceivable that a tandem foil system could exceed the Newman limit due to the strong unsteady vortex wake of the upstream turbine entraining additional energy into the path of the downstream turbine and maintaining pressures in the wake below ambient.