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Leptospira are bacteria that cause leptospirosis in both humans and animals. Human Leptospira infections in Uganda are suspected to arise from animal–human interactions. From a nationwide survey to determine Leptospira prevalence and circulating sequence types in Uganda, we tested 2030 livestock kidney samples, and 117 small mammals (rodents and shrews) using real-time PCR targeting the lipL32 gene. Pathogenic Leptospira species were detected in 45 livestock samples but not in the small mammals. The prevalence was 6.12% in sheep, 4.25% in cattle, 2.08% in goats, and 0.46% in pigs. Sequence typing revealed that Leptospira borgpetersenii, Leptospira kirschneri, and Leptospira interrogans are widespread across Uganda, with 13 novel sequence types identified. These findings enhance the East African MLST database and support the hypothesis that domesticated animals may be a source of human leptospirosis in Uganda, highlighting the need for increased awareness among those in close contact with livestock.
Dante Cicchetti, the architect of developmental psychopathology, has influenced so many of us in profound ways. One of his many contributions was in demonstrating the power of randomized controlled trials (RCTs) to study the effects of Child–Parent Psychotherapy (CPP). These RCTs have shed light on causal mechanisms in development. Following Cicchetti and colleagues’ work, we designed a brief home visiting program, Attachment and Biobehavioral Catch-up (ABC), to help parents respond in sensitive, nurturing ways, so as to enhance children’s attachment and self-regulatory capabilities. In the current study, we assessed adolescents’ reports of the closeness of their relationships with their mothers 12 years after their mothers completed the intervention. A total of 142 adolescents participated (47 randomized to ABC, 45 randomized to a control intervention, and 50 from a low-risk comparison group). Adolescents whose mothers had been randomized to ABC reported closer relationships with their mothers than adolescents randomized to the control condition, with significant differences seen on approval, support, companionship, and emotional support subscales. Consistent with Cicchetti et al.’s work, these results provide powerful evidence of the long-term effects of an early parenting intervention.
Using Otoplan software, it is possible to measure the cochlea before cochlear implant surgery. Until now, computed tomography (CT) of the cochlea has been necessary for this purpose. The aim of this study was to find out whether measuring the cochlea with magnetic resonance imaging (MRI) using Otoplan is possible with the same accuracy.
Methods
The cochlea of 44 patients of the local cochlear implant centre was measured by Otoplan using high-resolution CT-bone and MRI images, and the determined lengths were compared.
Results
No significant difference was found between the cochlear lengths measured, regardless of whether the length measurement was based on a CT or an MRI data set.
Conclusion
For the determination of cochlear length prior to cochlear implant surgery, MRI images are just as suitable as CT images, therefore CT is not mandatory for length measurement by Otoplan, which could reduce the patient's radiation exposure.
Helium or neopentane can be used as surrogate gas fill for deuterium (D2) or deuterium-tritium (DT) in laser-plasma interaction studies. Surrogates are convenient to avoid flammability hazards or the integration of cryogenics in an experiment. To test the degree of equivalency between deuterium and helium, experiments were conducted in the Pecos target chamber at Sandia National Laboratories. Observables such as laser propagation and signatures of laser-plasma instabilities (LPI) were recorded for multiple laser and target configurations. It was found that some observables can differ significantly despite the apparent similarity of the gases with respect to molecular charge and weight. While a qualitative behaviour of the interaction may very well be studied by finding a suitable compromise of laser absorption, electron density, and LPI cross sections, a quantitative investigation of expected values for deuterium fills at high laser intensities is not likely to succeed with surrogate gases.
Individuals with major depressive disorder (MDD) are observed to have reduced plasma nitrate levels and plasma nitric oxide (NO) metabolites (Chrapko et al., 2004; Garcia et al., 2011). Endothelial cell dependent dilation of vascular smooth muscle function has been observed to be blunted in adults with Major Depressive Disorder (MDD) and mediated by NO-dependent dilation (Greaney et al., 2019). Certain vegetables and fruits are particularly high in dietary nitrates, which is reduced to nitric oxide in the stomach, entering intravascular circulation, and acting as a potent dilator, blood pressure reducing, and vasoprotective substance (Webb et al., 2008). In older adults, dietary nitrates which are found in certain vegetables and fruits (e.g., green leafy vegetables) is shown to increase cerebral blood perfusion in frontal lobe white matter between the dorsolateral prefrontal and anterior cingulate cortex, regions particularly implicated in cognitive functioning (Presley et al., 2011). Recently, Morris et al. (2018) observed that in older adults from the Memory and Aging Project (MAP), the highest quintile of dietary nitrate intake was associated with slower cognitive decline than that of the lowest quintile of nitrate intake. Although viewing the extremes of dietary nitrate intake reveals valuable information, the present study investigated the association of all levels of dietary nitrate intake with cognition and depression among older adults in the same MAP dataset.
Participants and Methods:
The sample included 461 community dwelling older adults (Mage=80; Medu =14.9, 74% female) from the MAP study (Bennett et al., 2012). The measures used for the present study include: the Center for Epidemiological Studies Depression Scale (CESD, depression), a neuropsychological battery (global cognition, perceptual organization and semantic memory), and a dietary nutrient analysis of the food frequency questionnaire (FFQ, nitrate).
Results:
Using Pearson correlations we observed that increased dietary nitrate intake was associated with increased global cognition (r(458) = .100, p = .031), perceptual organization (r(448) = .095, p = .04) and semantic memory (r(453) = .142, p = .002). Furthermore, we observed that dietary nitrate intake was associated with lower depression severity (r(459) = -.132, p = .004).
Conclusions:
The present study’s results revealed that in a sample of community dwelling older adults, eating more nitrate rich foods is not only associated with improved cognition similar to findings of Morris et al. (2018), it is also associated with lower levels of depression. This further extends the Morris et al. (2018) study by suggesting that it is not only those older adults who eat the highest quantity of nitrate rich foods that can benefit from higher levels of nitrate intake. Overall, this study reveals that older adults who increase their dietary nitrate intake may improve their mood and thinking ability.
Our limited knowledge of the climate prevailing over Europe during former glaciations is the main obstacle to reconstruct the past evolution of the ice coverage over the Alps by numerical modelling. To address this challenge, we perform a two-step modelling approach: First, a regional climate model is used to downscale the time slice simulations of a global earth system model in high resolution, leading to climate snapshots during the Last Glacial Maximum (LGM) and the Marine Isotope Stage 4 (MIS4). Second, we combine these snapshots and a climate signal proxy to build a transient climate over the last glacial period and force the Parallel Ice Sheet Model to simulate the dynamical evolution of glaciers in the Alps. The results show that the extent of modelled glaciers during the LGM agrees with several independent key geological imprints, including moraine-based maximal reconstructed glacial extents, known ice transfluences and trajectories of erratic boulders of known origin and deposition. Our results highlight the benefit of multiphysical coupled climate and glacier transient modelling over simpler approaches to help reconstruct paleo glacier fluctuations in agreement with traces they have left on the landscape.
Valbenazine is a once-daily VMAT2 inhibitor approved for the treatment of tardive dyskinesia (TD), a persistent and potentially disabling movement disorder associated with prolonged exposure to antipsychotics, antiemetics, and other dopamine receptor blocking agents. The efficacy, safety, and tolerability of valbenazine has been established in several phase 3 trials, including a long-term study (KINECT 4 [NCT02405091]) in which participants received open-label valbenazine (40 or 80 mg) for 48 weeks. Post hoc analyses of KINECT 4 data were conducted to assess patterns of treatment response.
Methods
Data from KINECT 4 treatment completers (participants who reached the Week 48 visit and had the longest duration of treatment) were analyzed post hoc. TD was assessed using the Abnormal Involuntary Movement Scale (AIMS) total score (sum of items 1–7, as rated by the study investigator), the Clinical Global Impression of Change-Tardive Dyskinesia (CGI-TD), and the Patient Global Impression of Change (PGIC). Analyses were conducted at Week 8 (first study visit after the valbenazine dose-optimization period) and Week 48 using the following definitions of response: ≥50% and ≥70% improvement from baseline in AIMS total score; rating of “much improved” or “very much improved” (score ≤2) on the CGI-TD and PGIC.
Results
Of the 167 participants who entered KINECT 4, 103 (62%) were treatment completers and included for analysis. Of these 103 participants, 39% and 86% met the ≥50% AIMS response threshold at Weeks 8 and 48, respectively. The percentages of participants who met the highly rigorous AIMS ≥70% response threshold at Weeks 8 and 48 were 17% and 52%, respectively. Of the 40 participants with AIMS ≥50% total score improvement at Week 8, 95% also met this threshold at Week 48 (“sustained response”). Of the 63 participants with <50% AIMS improvement at Week 8, 81% achieved the ≥50% response threshold by end of treatment at Week 48. The proportion of participants meeting the threshold for CGI-TD response also increased over time, from 50% at Week 8 to 92% at Week 48. PGIC results were similar, with response rates of 53% and 88% at Weeks 8 and 48, respectively.
Conclusions
Post hoc analyses of data from a 48-week, open-label study of once-daily valbenazine showed that the proportion of participants meeting rigorous treatment response thresholds increased over time. By the end of treatment at Week 48, >80% of participants demonstrated robust improvements in TD, as assessed using the AIMS (≥50% improvement), CGI-TD (score ≤2), and PGIC (score ≤2).
The role of domestic public opinion is an important topic in research on international negotiations, yet we know little about how exactly it manifests itself. We focus on government rhetoric during negotiations and develop a conceptual distinction between implicit and explicit manifestations of public opinion. Drawing on a database of video recordings of negotiations of the Council of the European Union and a quantitative text analysis of government speeches, we find that public opinion matters implicitly, with the exact pattern depending on governments’ stance toward the EU. Pro-EU governments are responsive to public opinion in their support for compromises and attempts to stall negotiations, whereas Euroskeptic governments tend to remain silent when confronted with a public positively disposed toward the EU. Our results show that although governments implicitly represent public opinion, they do not systematically invoke their voters explicitly, suggesting the public matters but in different ways than often assumed.
Depression affects approximately 27% of adults with chronic kidney disease (CKD) and end-stage kidney failure (ESKF). Depression in this population is associated with impaired quality of life and increased mortality. The extent of inflammation and the impact on depression in CKD/ESKF is yet to be established. Through a systematic literature review and meta-analysis, we aim to understand the relationship between depression and inflammation in CKD/ESKF patients.
Methods
We searched nine electronic databases for published studies until January 2022. Titles and abstracts were screened against inclusion and exclusion criteria. Data extraction and study quality assessment was carried out independently by two reviewers. A meta-analysis was carried out where appropriate; otherwise a narrative review of studies was completed.
Results
Sixty studies met our inclusion criteria and entered the review (9481 patients included in meta-analysis). Meta-analysis of cross-sectional associations revealed significantly higher levels of pro-inflammatory biomarkers; C-reactive protein; Interleukin 6 (IL-6) and tumour necrosis factor-alpha in patients with depressive symptoms (DS) compared to patients without DS. Significantly lower levels of anti-inflammatory cytokine IL-10 were found in patients with DS compared to patients without DS. Considerable heterogeneity was detected in the analysis for most inflammatory markers.
Conclusion
We found evidence for an association of higher levels of pro-inflammatory and lower anti-inflammatory cytokines and DS in patients with CKD/ESKF. Clinical trials are needed to investigate whether anti-inflammatory therapies will be effective in the prevention and treatment of DS in these patients with multiple comorbidities.
Recently, the existence of so-called granular bubbles and droplets has been demonstrated experimentally. Granular bubbles and droplets are clusters of particles that respectively rise and sink if submerged in an aerated and vibrated bed of another granular material of different size and/or density. However, currently, there is no model that explains the coherent motion of these clusters and predicts the transition between a rising and sinking motion. Here, we propose an analytical model predicting accurately the neutral buoyancy limit of a granular bubble/droplet. This model allows the compilation of a regime map identifying five distinct regimes of granular bubble/droplet motion.
The dating of pollen grains is emerging as the method of choice for lacustrine climate archives that contain few datable macrofossils. Due to the need for high-purity pollen concentrates, new methods are constantly being developed to precisely separate pollen grains. Flow cytometry represents a promising alternative to conventional approaches, enabling the identification of pollen grains through fluorescence and rapid separation for radiocarbon analysis using accelerator mass spectrometry, which has so far been limited to sediments with a high proportion of conifer pollen. We present a revised method for processing large sediment samples, resulting in high-purity pollen and spore concentrates. Using this approach small- to medium-sized pollen and bryophyte spores were isolated from Lake Van sediment samples (Eastern Anatolia, Turkey) in sufficient purity for radiocarbon dating. However, a systematic age discrepancy between pollen and bryophyte spore concentrates was noted. By adapting the chemical and cytometric methods, pure pollen concentrates can be created for sediments with low organic content enabling age determination of climate archives with a low proportion of large pollen or low pollen concentration.
Expressive writing about a traumatic event is promising in treating posttraumatic stress disorder (PTSD) symptoms in adult trauma survivors. To date, the comparative efficacy and acceptability of this approach is uncertain. Therefore, we aimed to examine the comparative efficacy and acceptability of expressive writing treatments.
Methods
We included 44 RCTs with 7724 participants contributing 54 direct comparisons between expressive writing (EW), enhanced writing (i.e. including additional therapist contact or individualized writing assignments; EW+), PTSD psychotherapies (PT), neutral writing (NW), and waiting-list control (WL).
Results
EW, EW+, PT, and NW were statistically significantly more efficacious than WL at the longest available follow-up, with SMDs (95% CI) of −0.78 (−1.10 to −0.46) for PT, −0.81 (−1.02 to −0.61) for EW+ , −0.43 (−0.65 to −0.21) for EW, and −0.37 (−0.61 to −0.14) for NW. We found small to moderate differences between the active treatments. At baseline mean PTSD severity was significantly lower in EW+ compared with WL. We found considerable heterogeneity and inconsistency and we found elevated risk of bias in at least one of the bias dimensions in all studies. When EW+-WL comparisons were excluded from the analyses EW+ was no longer superior compared with EW.
Conclusions
The summarized evidence confirms that writing treatments may contribute to improving PTSD symptoms in medium to long-term. Methodological issues in the available evidence hamper definite conclusions regarding the comparative efficacy and acceptability of writing treatments. Adequately sized comparative randomized controlled trials preferably including all four active treatment approaches, reporting long-term data, and including researchers with balanced preferences are needed.
Despite the importance of wine in the Iron Age Mediterranean, known structures associated with its production are rare. Recent excavations at Phoenician Tell el-Burak have now revealed the first Iron Age wine press in Lebanon. Its remarkable state of preservation enables a systematic study of its plaster to be made as well as a comparison with two other plastered installations at the site. Archaeometric analyses offer new data concerning the composition and technology of Iron Age lime-plaster production, confirming the existence of a local and innovative tradition of plaster production in southern Phoenicia. These results contribute to the wider discussion of Phoenician technology in the broader Iron Age Mediterranean.
The typical onset of schizophrenia coincides with the maturational peak in cognition; however, for a significant proportion of patients the onset is before age 18 and after age 30 years. While cognitive deficits are considered core features of schizophrenia, few studies have directly examined the impact of age of illness onset on cognition.
Methods
The aim of the study was to examine if the effects of age on cognition differ between healthy controls (HCs) and patients with schizophrenia at illness onset. We examined 156 first-episode antipsychotic-naïve patients across a wide age span (12–43 years), and 161 age- and sex-matched HCs. Diagnoses were made according to ICD-10 criteria. Cognition was assessed using the Brief Assessment of Cognition in Schizophrenia (BACS), and IQ was estimated using subtests from the Wechsler adult- or child-intelligence scales. Multivariate analysis of covariance (MANCOVA) was used to examine linear and quadratic effects of age on cognitive scores and interactions by group, including sex and parental socioeconomic status as covariates.
Results
There was a significant overall effect of age on BACS and IQ (p < 0.001). Significant group-by-age interactions for verbal memory (for age-squared, p = 0.009), and digit sequencing (for age, p = 0.01; age-squared, p < 0.001), indicated differential age-related trajectories between patients and HCs.
Conclusions
Cognitive functions showing protracted maturation into adulthood, such as verbal memory and verbal working memory, may be particularly impaired in both early- and late-schizophrenia onset. Our findings indicate a potential interaction between the timing of neurodevelopmental maturation and a possible premature age effect in late-onset schizophrenia.
Weight gain among psychiatric inpatients is a widespread phenomenon. This change in body mass index (BMI) can be caused by several factors. Based on recent research, we assume the following factors are related to weight gain during psychiatric inpatient treatment: psychiatric medication, psychiatric diagnosis, sex, age, weight on admission and geographic region of treatment.
876 of originally recruited 2328 patients met the criteria for our analysis. Patients were recruited and examined in mental health care centres in Nigeria (N=265), Japan (N=145) and Western-Europe (Denmark, Germany and Switzerland; N=466).
There was a significant effect of psychiatric medication, psychiatric diagnoses and geographic region, but not age and sex, on BMI changes. Geographic region had a significant effect on BMI change, with Nigerian patients gaining significantly more weight than Japanese and Western European patients. Moreover, geographic region influenced the type of psychiatric medication prescribed and the psychiatric diagnoses. The diagnoses and psychiatric medication prescribed had a significant effect on BMI change.
In conclusion, we consider weight gain as a multifactorial phenomenon that is influenced by several factors. One can discuss a number of explanations for our findings, such as different clinical practices in the geographical regions (prescribing or admission strategies and access-to-care aspects), as well as socio-economic and cultural differences.
In the 2015 review paper ‘Petawatt Class Lasers Worldwide’ a comprehensive overview of the current status of high-power facilities of ${>}200~\text{TW}$ was presented. This was largely based on facility specifications, with some description of their uses, for instance in fundamental ultra-high-intensity interactions, secondary source generation, and inertial confinement fusion (ICF). With the 2018 Nobel Prize in Physics being awarded to Professors Donna Strickland and Gerard Mourou for the development of the technique of chirped pulse amplification (CPA), which made these lasers possible, we celebrate by providing a comprehensive update of the current status of ultra-high-power lasers and demonstrate how the technology has developed. We are now in the era of multi-petawatt facilities coming online, with 100 PW lasers being proposed and even under construction. In addition to this there is a pull towards development of industrial and multi-disciplinary applications, which demands much higher repetition rates, delivering high-average powers with higher efficiencies and the use of alternative wavelengths: mid-IR facilities. So apart from a comprehensive update of the current global status, we want to look at what technologies are to be deployed to get to these new regimes, and some of the critical issues facing their development.
The analysis of political texts from parliamentary speeches, party manifestos, social media, or press releases forms the basis of major and growing fields in political science, not least since advances in “text-as-data” methods have rendered the analysis of large text corpora straightforward. However, a lot of sources of political speech are not regularly transcribed, and their on-demand transcription by humans is prohibitively expensive for research purposes. This class includes political speech in certain legislatures, during political party conferences as well as television interviews and talk shows. We showcase how scholars can use automatic speech recognition systems to analyze such speech with quantitative text analysis models of the “bag-of-words” variety. To probe results for robustness to transcription error, we present an original “word error rate simulation” (WERSIM) procedure implemented in $R$. We demonstrate the potential of automatic speech recognition to address open questions in political science with two substantive applications and discuss its limitations and practical challenges.
To assess the prevalence of prediabetes and metabolic abnormalities among overweight or obese clozapine- or olanzapine-treated schizophrenia patients, and to identify characteristics of the schizophrenia group with prediabetes.
Methods
A cross-sectional study assessing the presence of prediabetes and metabolic abnormalities in schizophrenia clozapine- or olanzapine-treated patients with a body mass index (BMI) ≥27 kg/m2. Procedures were part of the screening process for a randomized, placebo-controlled trial evaluating liraglutide vs placebo for improving glucose tolerance. For comparison, an age-, sex-, and BMI-matched healthy control group without psychiatric illness and prediabetes was included. Prediabetes was defined as elevated fasting plasma glucose and/or impaired glucose tolerance and/or elevated glycated hemoglobin A1c.
Results
Among 145 schizophrenia patients (age = 42.1 years; males = 59.3%) on clozapine or olanzapine (clozapine/olanzapine/both: 73.8%/24.1%/2.1%), prediabetes was present in 69.7% (101 out of 145). While schizophrenia patients with and without prediabetes did not differ regarding demographic, illness, or antipsychotic treatment variables, metabolic abnormalities (waist circumference: 116.7±13.7 vs 110.1±13.6 cm, P = 0.007; triglycerides: 2.3±1.4 vs 1.6±0.9 mmol/L, P = 0.0004) and metabolic syndrome (76.2% vs 40.9%, P<0.0001) were significantly more pronounced in schizophrenia patients with vs without prediabetes. The age-, sex-, and BMI-matched healthy controls had significantly better glucose tolerance compared to both groups of patients with schizophrenia. The healthy controls also had higher levels of high-density lipoprotein compared to patients with schizophrenia and prediabetes.
Conclusion
Prediabetes and metabolic abnormalities were highly prevalent among the clozapine- and olanzapine-treated patients with schizophrenia, putting these patients at great risk for later type 2 diabetes and cardiovascular disease. These results stress the importance of identifying and adequately treating prediabetes and metabolic abnormalities among clozapine- and olanzapine-treated patients with schizophrenia.
The deep subsurface of other planetary bodies is of special interest for robotic and human exploration. The subsurface provides access to planetary interior processes, thus yielding insights into planetary formation and evolution. On Mars, the subsurface might harbour the most habitable conditions. In the context of human exploration, the subsurface can provide refugia for habitation from extreme surface conditions. We describe the fifth Mine Analogue Research (MINAR 5) programme at 1 km depth in the Boulby Mine, UK in collaboration with Spaceward Bound NASA and the Kalam Centre, India, to test instruments and methods for the robotic and human exploration of deep environments on the Moon and Mars. The geological context in Permian evaporites provides an analogue to evaporitic materials on other planetary bodies such as Mars. A wide range of sample acquisition instruments (NASA drills, Small Planetary Impulse Tool (SPLIT) robotic hammer, universal sampling bags), analytical instruments (Raman spectroscopy, Close-Up Imager, Minion DNA sequencing technology, methane stable isotope analysis, biomolecule and metabolic life detection instruments) and environmental monitoring equipment (passive air particle sampler, particle detectors and environmental monitoring equipment) was deployed in an integrated campaign. Investigations included studying the geochemical signatures of chloride and sulphate evaporitic minerals, testing methods for life detection and planetary protection around human-tended operations, and investigations on the radiation environment of the deep subsurface. The MINAR analogue activity occurs in an active mine, showing how the development of space exploration technology can be used to contribute to addressing immediate Earth-based challenges. During the campaign, in collaboration with European Space Agency (ESA), MINAR was used for astronaut familiarization with future exploration tools and techniques. The campaign was used to develop primary and secondary school and primary to secondary transition curriculum materials on-site during the campaign which was focused on a classroom extra vehicular activity simulation.