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Progressive brain structural MRI changes are described in schizophrenia and have been ascribed to both illness progression and antipsychotic treatment. We investigated treatment effects, in terms of total cumulative antipsychotic dose, efficacy and tolerability, on brain structural changes over the first 24 months of treatment in schizophrenia.
A prospective, 24-month, single-site cohort study in 99 minimally treated patients with first-episode schizophrenia, schizophreniform and schizoaffective disorder, and 98 matched healthy controls. We treated the patients according to a fixed protocol with flupenthixol decanoate, a long-acting injectable antipsychotic. We assessed psychopathology, cognition, extrapyramidal symptoms and BMI, and acquired MRI scans at months 0, 12 and 24. We selected global cortical thickness, white matter volume and basal ganglia volume as the regions of interest.
The only significant group × time interaction was for basal ganglia volumes. However, patients, but not controls, displayed cortical thickness reductions and increases in white matter and basal ganglia volumes. Cortical thickness reductions were unrelated to treatment. White matter volume increases were associated with lower cumulative antipsychotic dose, greater improvements in psychopathology and cognition, and more extrapyramidal symptoms. Basal ganglia volume increases were associated with greater improvements in psychopathology, greater increases in BMI and more extrapyramidal symptoms.
We provide evidence for plasticity in white matter and basal ganglia associated with antipsychotic treatment in schizophrenia, most likely linked to the dopamine blocking actions of these agents. Cortical changes may be more closely related to the neurodevelopmental, non-dopaminergic aspects of the illness.
This consensus statement by the Society for Healthcare Epidemiology of America (SHEA) and the Society for Post-Acute and Long-Term Care Medicine (AMDA), the Association for Professionals in Epidemiology and Infection Control (APIC), the HIV Medicine Association (HIVMA), the Infectious Diseases Society of America (IDSA), the Pediatric Infectious Diseases Society (PIDS), and the Society of Infectious Diseases Pharmacists (SIDP) recommends that coronavirus disease 2019 (COVID-19) vaccination should be a condition of employment for all healthcare personnel in facilities in the United States. Exemptions from this policy apply to those with medical contraindications to all COVID-19 vaccines available in the United States and other exemptions as specified by federal or state law. The consensus statement also supports COVID-19 vaccination of nonemployees functioning at a healthcare facility (eg, students, contract workers, volunteers, etc).
In a multicenter cohort of 963 adults hospitalized due to coronavirus disease 2019 (COVID-19), 5% had a proven hospital-acquired infection (HAI) and 21% had a proven, probable, or possible HAI. Risk factors for proven or probable HAIs included intensive care unit admission, dexamethasone use, severe COVID-19, heart failure, and antibiotic exposure upon admission.
The worldwide production of in vitro-produced embryos in livestock species continues to grow. The current gold standard for selecting quality oocytes and embryos is morphologic assessment, yet this method is subjective and varies based on experience. There is a need for a non-invasive, objective method of selecting viable oocytes and embryos. The aim of this study was to determine if ooplasm area, diameter including zona pellucida (ZP), and ZP thickness of artificially activated oocytes and in vitro fertilized (IVF) zygotes are indicative of development success in vitro and correlated with embryo quality, as assessed by total blastomere number. Diameter affected the probability of development to the blastocyst stage in activated oocytes on day 7 (P < 0.01) and day 8 (P < 0.001), and had a tendency to affect IVF zygotes on day 8 (P = 0.08). Zona pellucida thickness affected the probability of development on day 7 (P < 0.01) and day 8 (P < 0.001) in activated oocytes, and day 8 for IVF zygotes (P < 0.05). An interaction between ZP thickness and diameter was observed on days 7 and 8 (P < 0.05) in IVF zygotes. Area did not significantly affect the probability of development, but was positively correlated with blastomere number on day 8 for IVF zygotes (P = 0.01, conditional R2 = 0.09). Physical parameters of bovine zygotes have the potential for use as a non-invasive, objective selection method. Upon further development, methods used in this study could be integrated into embryo production systems to improve IVF success.
Antibiotics are among the most common medications prescribed in nursing homes. The annual prevalence of antibiotic use in residents of nursing homes ranges from 47% to 79%, and more than half of antibiotic courses initiated in nursing-home settings are unnecessary or prescribed inappropriately (wrong drug, dose, or duration). Inappropriate antibiotic use is associated with a variety of negative consequences including Clostridioides difficile infection (CDI), adverse drug effects, drug–drug interactions, and antimicrobial resistance. In response to this problem, public health authorities have called for efforts to improve the quality of antibiotic prescribing in nursing homes.
Typical enteropathogenic Escherichia coli (tEPEC) infection is a major cause of diarrhoea and contributor to mortality in children <5 years old in developing countries. Data were analysed from the Global Enteric Multicenter Study examining children <5 years old seeking care for moderate-to-severe diarrhoea (MSD) in Kenya. Stool specimens were tested for enteric pathogens, including by multiplex polymerase chain reaction for gene targets of tEPEC. Demographic, clinical and anthropometric data were collected at enrolment and ~60-days later; multivariable logistic regressions were constructed. Of 1778 MSD cases enrolled from 2008 to 2012, 135 (7.6%) children tested positive for tEPEC. In a case-to-case comparison among MSD cases, tEPEC was independently associated with presentation at enrolment with a loss of skin turgor (adjusted odds ratio (aOR) 2.08, 95% confidence interval (CI) 1.37–3.17), and convulsions (aOR 2.83, 95% CI 1.12–7.14). At follow-up, infants with tEPEC compared to those without were associated with being underweight (OR 2.2, 95% CI 1.3–3.6) and wasted (OR 2.5, 95% CI 1.3–4.6). Among MSD cases, tEPEC was associated with mortality (aOR 2.85, 95% CI 1.47–5.55). This study suggests that tEPEC contributes to morbidity and mortality in children. Interventions aimed at defining and reducing the burden of tEPEC and its sequelae should be urgently investigated, prioritised and implemented.
Praziquantel (PZQ) is the drug of choice for schistosomiasis. The potential drug resistance necessitates the search for adjunct or alternative therapies to PZQ. Previous functional genomics has shown that RNAi inhibition of Ca2+/calmodulin-dependent protein kinase II (CaMKII) gene in Schistosoma adult worms significantly improved the effectiveness of PZQ. Here we tested the in vitro efficacy of 15 selective and non-selective CaMK inhibitors against Schistosoma mansoni and showed that PZQ efficacy was improved against refractory juvenile parasites when combined with these CaMK inhibitors. By measuring CaMK activity and the mobility of adult S. mansoni, we identified two non-selective CaMK inhibitors, Staurosporine (STSP) and 1Naphthyl PP1 (1NAPP1), as promising candidates for further study. The impact of STSP and 1NAPP1 was investigated in mice infected with S. mansoni in the presence or absence of a sub-lethal dose of PZQ against 2- and 7-day-old schistosomula and adults. Treatment with STSP/PZQ induced a significant (47–68%) liver egg burden reduction compared with mice treated with PZQ alone. The findings indicate that the combination of STSP and PZQ dosages significantly improved anti-schistosomal activity compared to PZQ alone, demonstrating the potential of selective and non-selective CaMK/kinase inhibitors as a combination therapy with PZQ in treating schistosomiasis.
The ‘jumping to conclusions’ (JTC) bias is associated with both psychosis and general cognition but their relationship is unclear. In this study, we set out to clarify the relationship between the JTC bias, IQ, psychosis and polygenic liability to schizophrenia and IQ.
A total of 817 first episode psychosis patients and 1294 population-based controls completed assessments of general intelligence (IQ), and JTC, and provided blood or saliva samples from which we extracted DNA and computed polygenic risk scores for IQ and schizophrenia.
The estimated proportion of the total effect of case/control differences on JTC mediated by IQ was 79%. Schizophrenia polygenic risk score was non-significantly associated with a higher number of beads drawn (B = 0.47, 95% CI −0.21 to 1.16, p = 0.17); whereas IQ PRS (B = 0.51, 95% CI 0.25–0.76, p < 0.001) significantly predicted the number of beads drawn, and was thus associated with reduced JTC bias. The JTC was more strongly associated with the higher level of psychotic-like experiences (PLEs) in controls, including after controlling for IQ (B = −1.7, 95% CI −2.8 to −0.5, p = 0.006), but did not relate to delusions in patients.
Our findings suggest that the JTC reasoning bias in psychosis might not be a specific cognitive deficit but rather a manifestation or consequence, of general cognitive impairment. Whereas, in the general population, the JTC bias is related to PLEs, independent of IQ. The work has the potential to inform interventions targeting cognitive biases in early psychosis.
The present study examined empathy deficits in toddlerhood (age 14 to 36 months) as predictors of antisocial personality disorder (ASPD) symptoms and psychopathy measured by the Levenson Self-Report Psychopathy scale (Levenson, Kiehl, & Fitzpatrick, 1995) in adulthood (age 23 years) in 956 individuals from the Colorado Longitudinal Twin Study. Consistent with the hypothesis that antisocial behavior is associated with “active” rather than “passive” empathy deficits, early disregard for others, not lack of concern for others, predicted later ASPD symptoms. Early disregard for others was also significantly associated with factor 1 of the Levenson Self-Report Psychopathy Scale, which includes items assessing interpersonal and affective deficits, but not with factor 2, which includes items assessing impulsivity and poor behavioral control. The association between early disregard for others and psychopathy factor 2 was near zero after controlling for the shared variance between psychopathy factors 1 and 2. These results suggest that there is a propensity toward adulthood ASPD symptoms and psychopathy factor 1 that can be assessed early in development, which may help identify individuals most at risk for stable antisocial outcomes.
A higher incidence of psychotic disorders has been consistently reported among black and other minority ethnic groups, particularly in northern Europe. It is unclear whether these rates have changed over time.
We identified all individuals with a first episode psychosis who presented to adult mental health services between 1 May 2010 and 30 April 2012 and who were resident in London boroughs of Lambeth and Southwark. We estimated age-and-gender standardised incidence rates overall and by ethnic group, then compared our findings to those reported in the Aetiology and Ethnicity of Schizophrenia and Other Psychoses (ÆSOP) study that we carried out in the same catchment area around 10 years earlier.
From 9109 clinical records we identified 558 patients with first episode psychosis. Compared with ÆSOP, the overall incidence rates of psychotic disorder in southeast London have increased from 49.4 (95% confidence interval (CI) 43.6–55.3) to 63.1 (95% CI 57.3–69.0) per 100 000 person-years at risk. However, the overall incidence rate ratios (IRR) were reduced in some ethnic groups: for example, IRR (95% CI) for the black Caribbean group reduced from 6.7 (5.4–8.3) to 2.8 (2.1–3.6) and the ‘mixed’ group from 2.7 (1.8–4.2) to 1.4 (0.9–2.1). In the black African group, there was a negligible difference from 4.1 (3.2–5.3) to 3.5 (2.8–4.5).
We found that incidence rates of psychosis have increased over time, and the IRR varied by the ethnic group. Future studies are needed to investigate more changes over time and determinants of change.
The Colorado Twin Registry (CTR) is a population-based registry formed from birth and school records including twins born between 1968 and the present. Two previous reports on the CTR [Rhea et al., (2006). Twin Research and Human Genetics, 9, 941–949; Rhea et al., (2013).Twin Research and Human Genetics, 16, 351–357] covered developments in the CTR through 2012. This report briefly summarizes previously presented material on ascertainment and recruitment and the relationships between samples and studies, discusses developments since 2012 for four previously described twin samples, describes two new samples and their complementary studies and expands on two subjects briefly mentioned in the last report: a history of genotyping efforts involving CTR samples, and a survey of collaborations and consortia in which CTR twins have been included. The CTR remains an active resource for both ongoing, longitudinal research and the recruitment of new twin samples for newly identified research opportunities.
In the present study, we aimed to compare anthropometric indicators as predictors of mortality in a community-based setting.
We conducted a population-based longitudinal study nested in a cluster-randomized trial. We assessed weight, height and mid-upper arm circumference (MUAC) on children 12 months after the trial began and used the trial’s annual census and monitoring visits to assess mortality over 2 years.
Children aged 6–60 months during the study.
Of 1023 children included in the study at baseline, height-for-age Z-score, weight-for-age Z-score, weight-for-height Z-score and MUAC classified 777 (76·0 %), 630 (61·6 %), 131 (12·9 %) and eighty (7·8 %) children as moderately to severely malnourished, respectively. Over the 2-year study period, fifty-eight children (5·7 %) died. MUAC had the greatest AUC (0·68, 95 % CI 0·61, 0·75) and had the strongest association with mortality in this sample (hazard ratio = 2·21, 95 % CI 1·26, 3·89, P = 0·006).
MUAC appears to be a better predictor of mortality than other anthropometric indicators in this community-based, high-malnutrition setting in Niger.
We examine the effects of a temporary suspension of short-sale price tests on the options market. Consistent with the notion that put option trading substitutes for short selling, we find a significant reduction in put option volume. In addition, pressure on put option prices significantly declines, violations of the put-call parity become significantly less frequent, and option volume becomes less informed. Our findings add clarity to a long-standing debate on whether investors use options to circumvent equity short-selling restrictions.
Extra-care housing (ECH) has been hailed as a potential solution to some of the problems associated with traditional forms of social care, since it allows older people to live independently, while also having access to care and support if required. However, little longitudinal research has focused on the experiences of residents living in ECH, particularly in recent years. This paper reports on a longitudinal study of four ECH schemes in the United Kingdom. Older residents living in ECH were interviewed four times over a two-year period to examine how changes in their care needs were encountered and negotiated by care workers, managers and residents themselves. This paper focuses on how residents managed their own changing care needs within the context of ECH. Drawing upon theories of the third and fourth age, the paper makes two arguments. First, that transitions across the boundary between the third and fourth age are not always straightforward or irreversible and, moreover, can sometimes be resisted, planned-for and managed by older people. Second, that operational practices within ECH schemes can function to facilitate or impede residents’ attempts to manage this boundary.
Magic squares have long been popular in recreational mathematics. Their potential for introducing students to ideas in linear algebra was recognised over forty years ago in  and later in . More recently they have proved to be a fascinating topic for undergraduate exploration, especially when students have access to a computer algebra package . Some results on powers of magic square matrices can be found in ,  and . (Readers who google the title ‘Odd magic powers’ of Thompson’s paper  will be treated to a wide variety of non-mathematical exotica!)
In the National Institutes of Health (NIH) Clinical Center, patients colonized or infected with vancomycin-resistant Enterococcus (VRE) are placed in contact isolation until they are deemed “decolonized,” defined as having 3 consecutive perirectal swabs negative for VRE. Some decolonized patients later develop recurrent growth of VRE from surveillance or clinical cultures (ie, “recolonized”), although that finding may represent recrudescence or new acquisition of VRE. We describe the dynamics of VRE colonization and infection and their relationship to receipt of antibiotics.
In this retrospective cohort study of patients at the National Institutes of Health Clinical Center, baseline characteristics were collected via chart review. Antibiotic exposure and hospital days were calculated as proportions of VRE decolonized days. Using survival analysis, we assessed the relationship between antibiotic exposure and time to VRE recolonization in a subcohort analysis of 72 decolonized patients.
In total, 350 patients were either colonized or infected with VRE. Among polymerase chain reaction (PCR)-positive, culture (Cx)-negative (PCR+/Cx−) patients, PCR had a 39% positive predictive value for colonization. Colonization with VRE was significantly associated with VRE infection. Among 72 patients who met decolonization criteria, 21 (29%) subsequently became recolonized. VRE recolonization was 4.3 (P = .001) and 2.0 (P = .22) times higher in patients with proportions of antibiotic days and antianaerobic antibiotic days above the median, respectively.
Colonization is associated with clinical VRE infection and increased mortality. Despite negative perirectal cultures, re-exposure to antibiotics increases the risk of VRE recolonization.
The Cottar Tribe, who are the Locusts of the Land … they comprise the indolent, uncivilised and pauperism of the Estate … His Grace of Argyll never speculated money to such advantage as to get rid of them by all possible speed.
I would watch them and all those who are not industrious would most assuredly be deprived of their possessions. Nothing but harshness and dread I find will do, they are so naturally slothful and indolent.
I have daily, numerous applications for food … unless they work they must just starve.
AT 1 P.M. ON a Saturday afternoon at the end of August 1872, on the island of Mull within a small, felt-roofed blackhouse in the Ardfenaig steading, a very tall and heavily built man who had been feared the length and breadth of the islands of Mull, Iona and Tiree, and who had lain stretched out on a bed for the previous two weeks, gasped his last breath and died, having collapsed earlier at the steading. So began the myth of a man still passionately spoken about today, 145 years after his death. Vivid oral traditions have survived about his life on Mull during his twenty-six years there and his eighteen years on Tiree as Chamberlain for the Duke of Argyll. He is regarded in oral tradition as being one of the most notorious chamberlains in Argyllshire, if not Scotland, during the nineteenth century. His name was John Campbell, a Gaelic speaker from the island of Islay (see Figure 8). He became Chamberlain of the Inner Hebridean islands of Mull, Iona and Tiree at the time the potato blight arrived in the 1840s, which had such devastating consequences for all who lived there.
Oral tradition relates that dogs howled all night the day before he died with a premonition of his imminent death and that maggots had infiltrated his body so that ‘he became alive like a maggoty sheep’. After he died, ‘animals broke their ties and the barking of the Ardfenaig dogs were heard in Ardtun’.
To determine the effectiveness of a workplace wellness programme intervention in improving participants’ behaviour towards choosing a healthy diet and the correlation with health indicators.
A retrospective cohort study.
Wellness programme in the Midwest, USA.
Employees (n 12 636) who participated in a wellness programme for three consecutive years during years 2004 to 2013 and who completed web-based health risk questionnaires. The wellness programme included annual health screening, laboratory measures, health risk questionnaire and personalized health-care programme. Participants’ food group intakes, BMI and health indicators were compared between the first and last year of participation. McNemar’s non-parametric test was used for paired nominal data. Pearson correlations were computed for paired food and health indicator measurements. Correlations between dietary intake and BMI, cholesterol and TAG were computed using Pearson correlations and McNemar’s test.
There were negative correlations between intakes of fruits, vegetables, grains, dairy, healthy eating pattern and health outcome indicators such as BMI and TAG levels. Additionally, the percentage of employees who increased their consumption of fruits (16·88 v. 12·08 %, P<0·001), vegetables (15·20 v. 11·44 %, P<0·001) and dark green leafy vegetables (12·03 v. 7·27 %, P 0·001) was significantly higher than the percentage of participants who decreased their intake of these food groups during the third-year follow-up.
The wellness programme improved some health indicator parameters and had a positive impact on increasing participants’ intakes of fruits, vegetables and whole grains at the third year of follow-up.