Acceptance and Commitment Therapy plus usual care for improving quality of life in people with motor neuron disease (COMMEND): a multicentre, parallel, randomised controlled trial in the UK.

BACKGROUND: Motor neuron disease is a progressive, fatal neurodegenerative disease for which there is no cure. Acceptance and Commitment Therapy (ACT) is a psychological therapy incorporating acceptance, mindfulness, and behaviour change techniques. We aimed to evaluate the effectiveness of ACT plus usual care, compared with usual care alone, for improving quality of life in people with motor neuron disease. METHODS: We conducted a parallel, multicentre, two-arm randomised controlled trial in 16 UK motor neuron disease care centres or clinics. Eligible participants were aged 18 years or older with a diagnosis of definite or laboratory-supported probable, clinically probable, or possible familial or sporadic amyotrophic lateral sclerosis; progressive muscular atrophy; or primary lateral sclerosis; which met the World Federation of Neurology's El Escorial diagnostic criteria. Participants were randomly assigned (1:1) to receive up to eight sessions of ACT adapted for people with motor neuron disease plus usual care or usual care alone by a web-based system, stratified by site. Participants were followed up at 6 months and 9 months post-randomisation. Outcome assessors and trial statisticians were masked to treatment allocation. The primary outcome was quality of life using the McGill Quality of Life Questionnaire-Revised (MQOL-R) at 6 months post-randomisation. Primary analyses were multi-level modelling and modified intention to treat among participants with available data. This trial was pre-registered with the ISRCTN Registry (ISRCTN12655391). FINDINGS: Between Sept 18, 2019, and Aug 31, 2022, 435 people with motor neuron disease were approached for the study, of whom 206 (47%) were assessed for eligibility, and 191 were recruited. 97 (51%) participants were randomly assigned to ACT plus usual care and 94 (49%) were assigned to usual care alone. 80 (42%) of 191 participants were female and 111 (58%) were male, and the mean age was 63·1 years (SD 11·0). 155 (81%) participants had primary outcome data at 6 months post-randomisation. After controlling for baseline scores, age, sex, and therapist clustering, ACT plus usual care was superior to usual care alone for quality of life at 6 months (adjusted mean difference on the MQOL-R of 0·66 [95% CI 0·22-1·10]; d=0·46 [0·16-0·77]; p=0·0031). Moderate effect sizes were clinically meaningful. 75 adverse events were reported, 38 of which were serious, but no adverse events were deemed to be associated with the intervention. INTERPRETATION: ACT plus usual care is clinically effective for maintaining or improving quality of life in people with motor neuron disease. As further evidence emerges confirming these findings, health-care providers should consider how access to ACT, adapted for the specific needs of people with motor neuron disease, could be provided within motor neuron disease clinical services. FUNDING: National Institute for Health and Care Research Health Technology Assessment and Motor Neurone Disease Association.

Nomadic ecology shaped the highland geography of Asia's Silk Roads.

There are many unanswered questions about the evolution of the ancient 'Silk Roads' across Asia. This is especially the case in their mountainous stretches, where harsh terrain is seen as an impediment to travel. Considering the ecology and mobility of inner Asian mountain pastoralists, we use 'flow accumulation' modelling to calculate the annual routes of nomadic societies (from 750 m to 4,000 m elevation). Aggregating 500 iterations of the model reveals a high-resolution flow network that simulates how centuries of seasonal nomadic herding could shape discrete routes of connectivity across the mountains of Asia. We then compare the locations of known high-elevation Silk Road sites with the geography of these optimized herding flows, and find a significant correspondence in mountainous regions. Thus, we argue that highland Silk Road networks (from 750 m to 4,000 m) emerged slowly in relation to long-established mobility patterns of nomadic herders in the mountains of inner Asia.

Quality of rheumatoid arthritis recording in United Kingdom Clinical Practice Research Datalink Aurum.

PURPOSE: While several studies have assessed quality and completeness of recording acute medical events in Clinical Practice Research Datalink (CPRD) Aurum, evaluation of additional chronic conditions is warranted. METHODS: We selected patients with a first diagnosis of rheumatoid arthritis (RA) coded in their CPRD Aurum record between 2005 and 2019. We assessed quality of RA diagnosis by evaluating additional information in the patient record that would corroborate the diagnosis. We report recording of diagnoses, prescriptions, labs, and referrals expected to be present based on NICE guidelines for RA management. RESULTS: There were 53 083 patients with a first recorded RA diagnosis during the study period: 43606 (82%) patients had RA drug treatments in their record, 7596 (14%) had supporting codes without drug treatment, and 1881 (4%) patients had only a RA diagnoses recorded in their medical record with no supporting codes or RA treatments. Patients with RA diagnosis only were more likely to be first diagnosed in the earliest time period of study. Labs for diagnosing and monitoring RA were most common among patients with RA treatment. Analgesic and glucocorticoid prescriptions were common in all study patients but were highest among patients with RA treatment. Among patients with RA diagnosis only, the overwhelming majority had only one RA diagnosis recorded (76%). CONCLUSIONS: Our findings suggest that codes expected for monitoring and treatment of RA are routinely recorded in CPRD Aurum. These results support previous assessments, which found data recorded in CPRD Aurum to be of good quality for use in research.

The ultrasonographic appearance of renal medullary striations and their association with renal disease and renal histopathology in domestic cats.

Medullary striations (MS) have been anecdotally observed on ultrasound of feline kidneys; however, their significance is unknown. Aims of this retrospective, case control, pilot study were to describe the appearance, prevalence, and clinicopathological correlates of MS in a referral feline population. Still images from 1247 feline abdominal ultrasound studies performed between 2011 and 2021 were reviewed. Cats with MS were identified and compared with age-matched controls. Serum urea, creatinine, calcium, phosphate, and calcium-phosphate-product, plus urine specific gravity, urine protein: creatinine ratio (UPC), prevalence of active sediment (defined as > 5 red (RBC) or white blood cells (WBC) per high-power field) and prevalence of positive urine culture were compared between MS and control groups using the Mann-Whitney U test or Fisher's Exact test. Data are presented as median [range]. 27 cats were identified as having MS, giving a prevalence of 2.2% with a significantly higher proportion being seen in males (P = 0.018). Medullary striation cats had significantly higher UPC values than controls (0.46 [0.16-7.57] vs. 0.16 [0.07-2.27]; P = 0.006). Cats with MS were more likely to have active urinary sediments (39% vs 8%, P = 0.023), but no difference in prevalence of positive urinary cultures was observed between groups. There was no significant difference in other parameters between MS and control cats. Renal histopathology performed in three MS cats revealed focal regions of linear medullary fibrosis. Medullary striations are associated with proteinuria and urinary tract inflammation in cats, which may reflect renal tubular dysfunction and/or inflammation. Hence identification might allow for earlier detection of renal pathology.

Why has farming in Europe changed? A farmers' perspective on the development since the 1960s.

Farming in Europe has been the scene of several important socio-economic and environmental developments and crises throughout the last century. Therefore, an understanding of the historical driving forces of farm change helps identifying potentials for navigating future pathways of agricultural development. However, long-term driving forces have so far been studied, e.g. in anecdotal local case studies or in systematic literature reviews, which often lack context dependency. In this study, we bridged local and continental scales by conducting 123 oral history interviews (OHIs) with elderly farmers across 13 study sites in 10 European countries. We applied a driving forces framework to systematically analyse the OHIs. We find that the most prevalent driving forces were the introduction of new technologies, developments in agricultural markets that pushed farmers for farm size enlargement and technological optimisation, agricultural policies, but also cultural aspects such as cooperation and intergenerational arrangements. However, we find considerable heterogeneity in the specific influence of individual driving forces across the study sites, implying that generic assumptions about the dynamics and impacts of European agricultural change drivers hold limited explanatory power on the local scale. Our results suggest that site-specific factors and their historical development will need to be considered when addressing the future of agriculture in Europe in a scientific or policy context. Supplementary Information: The online version contains supplementary material available at 10.1007/s10113-023-02150-y.

Farmer surveys in Europe suggest that specialized, intensive farms were more likely to perceive negative impacts from COVID-19.

It has been shown that the COVID-19 pandemic affected some agricultural systems more than others, and even within geographic regions, not all farms were affected to the same extent. To build resilience of agricultural systems to future shocks, it is key to understand which farms were affected and why. In this study, we examined farmers' perceived robustness to COVID-19, a key resilience capacity. We conducted standardized farmer interviews (n = 257) in 15 case study areas across Europe, covering a large range of socio-ecological contexts and farm types. Interviews targeted perceived livelihood impacts of the COVID-19 pandemic on productivity, sales, price, labor availability, and supply chains in 2020, as well as farm(er) characteristics and farm management. Our study corroborates earlier evidence that most farms were not or only slightly affected by the first wave(s) of the pandemic in 2020, and that impacts varied widely by study region. However, a significant minority of farmers across Europe reported that the pandemic was "the worst crisis in a lifetime" (3%) or "the worst crisis in a decade" (7%). Statistical analysis showed that more specialized and intensive farms were more likely to have perceived negative impacts. From a societal perspective, this suggests that highly specialized, intensive farms face higher vulnerability to shocks that affect regional to global supply chains. Supporting farmers in the diversification of their production systems while decreasing dependence on service suppliers and supply chain actors may increase their robustness to future disruptions. Supplementary Information: The online version contains supplementary material available at 10.1007/s13593-022-00820-5.

Size-Exclusion Chromatography Separation Reveals That Vesicular and Non-Vesicular Small RNA Profiles Differ in Cell Free Urine.

Urinary extracellular vesicles (EVs) and their RNA cargo are a novel source of biomarkers for various diseases. We aimed to identify the optimal method for isolating small (<200 nm) EVs from human urine prior to small RNA analysis. EVs from filtered healthy volunteer urine were concentrated using three methods: ultracentrifugation (UC); a precipitation-based kit (PR); and ultrafiltration (UF). EVs were further purified by size-exclusion chromatography (SEC). EV preparations were analysed with transmission electron microscopy (TEM), Western blotting, nanoparticle tracking analysis (NTA) and an Agilent Bioanalyzer Small RNA kit. UF yielded the highest number of particles both before and after SEC. Small RNA analysis from UF-concentrated urine identified two major peaks at 10-40 nucleotides (nt) and 40-80 nt. In contrast, EV preparations obtained after UC, PR or SEC combined with any concentrating method, contained predominantly 40-80 nt sized small RNA. Protein fractions from UF+SEC contained small RNA of 10-40 nt in size (consistent with miRNAs). These data indicate that most of the microRNA-sized RNAs in filtered urine are not associated with small-sized EVs, and highlights the importance of removing non-vesicular proteins and RNA from urine EV preparations prior to small RNA analysis.

Quality and completeness of diagnoses recorded in the new CPRD Aurum Database: evaluation of pulmonary embolism.

PURPOSE: The Clinical Practice Research Datalink (CPRD) now provides a new medical record database, CPRD Aurum. This is the first of several studies being undertaken to assess the quality and completeness of CPRD Aurum data for research endeavors. METHODS: We identified patients with a pulmonary embolism (PE) diagnosis from a random sample of 50 000 patients in CPRD Aurum and compared the diagnoses using data from Hospital Episode Statistics (HES). We calculated the proportion of PE cases recorded in CPRD Aurum who also had a PE diagnosis recorded in HES. We also evaluated completeness by identifying all PE diagnoses in HES and calculating the proportion also present in CPRD Aurum. RESULTS: The study included 781 PE patients: 580 had a PE in CPRD Aurum, 632 had a PE in HES, and 431 had a PE in both. The proportion of patients with anticoagulated PE in CPRD Aurum confirmed by HES was 76.8%. The completeness of primary hospitalized PE HES events compared to CPRD Aurum was 79.1%. In most instances, there was a plausible explanation for the presence of a PE in only one of the two data sources. CONCLUSIONS: The results of this study are reassuring and suggest that the correctness (eg, quality, accuracy) and completeness of diagnosis information in CPRD Aurum are promising with respect to serious acute conditions that require medical attention. Evaluation of other data elements will provide additional insight into this new data resource and its utility for medical research.

CPRD Aurum database: Assessment of data quality and completeness of three important comorbidities.

PURPOSE: The Clinical Practice Research Datalink (CPRD) now provides a new medical record database, CPRD Aurum. This is the second of several studies being undertaken to assess the quality of CPRD Aurum data for research. METHODS: We included patients aged 20+, with at least one lab test result of any type from a random sample of 50 000 patients in CPRD Aurum. We assessed whether diagnosis codes for type 2 diabetes, hyperlipidemia, and iron deficiency or unspecified anemia were accompanied by supporting codes including lab results and treatments (correctness) and whether lab results, treatments, or other codes indicate a missing diagnosis record (completeness). RESULTS: Among 37 502 patients in CPRD Aurum, correctness of type 2 diabetes, hyperlipidemia, and anemia diagnoses was high (99%, 93%, and 97%, respectively). Completeness was only high for type 2 diabetes (94%-98%); completeness for hypercholesterolemia and anemia diagnoses was modest even when the presence of treatments and lab results indicated the conditions were likely present (51%-59% and 58%-70%, respectively). CONCLUSIONS: Our findings indicate that for studies of type 2 diabetes, hyperlipidemia, and iron deficiency or unspecified anemia, the diagnosis code is likely to be correct where present. However, a significant proportion of cases of hyperlipidemia or anemia will be missed if only diagnosis codes are used to select patients with these conditions. Researchers should consider using treatments, supporting codes, and, when available, lab data to supplement diagnosis codes and enhance case capture when including these conditions in studies using CPRD Aurum.

Neural correlates of the LSD experience revealed by multimodal neuroimaging.

Lysergic acid diethylamide (LSD) is the prototypical psychedelic drug, but its effects on the human brain have never been studied before with modern neuroimaging. Here, three complementary neuroimaging techniques: arterial spin labeling (ASL), blood oxygen level-dependent (BOLD) measures, and magnetoencephalography (MEG), implemented during resting state conditions, revealed marked changes in brain activity after LSD that correlated strongly with its characteristic psychological effects. Increased visual cortex cerebral blood flow (CBF), decreased visual cortex alpha power, and a greatly expanded primary visual cortex (V1) functional connectivity profile correlated strongly with ratings of visual hallucinations, implying that intrinsic brain activity exerts greater influence on visual processing in the psychedelic state, thereby defining its hallucinatory quality. LSD's marked effects on the visual cortex did not significantly correlate with the drug's other characteristic effects on consciousness, however. Rather, decreased connectivity between the parahippocampus and retrosplenial cortex (RSC) correlated strongly with ratings of "ego-dissolution" and "altered meaning," implying the importance of this particular circuit for the maintenance of "self" or "ego" and its processing of "meaning." Strong relationships were also found between the different imaging metrics, enabling firmer inferences to be made about their functional significance. This uniquely comprehensive examination of the LSD state represents an important advance in scientific research with psychedelic drugs at a time of growing interest in their scientific and therapeutic value. The present results contribute important new insights into the characteristic hallucinatory and consciousness-altering properties of psychedelics that inform on how they can model certain pathological states and potentially treat others.

Development and Validation of the Morphing Fear Questionnaire (MFQ).

Morphing fears (also called transformation obsessions) involve concerns that a person may become contaminated by and acquire undesirable characteristics of others. These symptoms are found in patients with obsessive-compulsive disorder (OCD) and are thought to be related to mental contamination. Given the high levels of distress and interference morphing fears can cause, a reliable and valid assessment measure is needed. This article describes the development and evaluation of the Morphing Fear Questionnaire (MFQ), a 13-item measure designed to assess for the presence and severity of morphing fears. A sample of 900 participants took part in the research. Of these, 140 reported having a current diagnosis of OCD (SR-OCD) and 760 reported never having had OCD (N-OCD; of whom 24 reported a diagnosis of an anxiety disorder and 23 reported a diagnosis of depression). Factor structure, reliability and construct and criterion-related validity were investigated. Exploratory and confirmatory factor analyses supported a one-factor structure replicable across the N-OCD and SR-OCD group. The MFQ was found to have high internal consistency and good temporal stability and showed significantly greater associations with convergent measures (assessing obsessive-compulsive symptoms, mental contamination, thought-action fusion and magical thinking) than with divergent measures (assessing depression and anxiety). Moreover, the MFQ successfully discriminated between the SR-OCD sample and the N-OCD group, anxiety disorder sample and depression sample. These findings suggest that the MFQ has sound psychometric properties and that it can be used to assess morphing fear. Clinical implications are discussed. Copyright © 2015 John Wiley & Sons, Ltd. KEY PRACTITIONER MESSAGE: Little remains known about morphing fears, but it is an important area of investigation due to symptoms being highly distressing and often debilitating Because morphing fears commonly present as obscure symptoms, they may not be recognized as a type of OCD The MFQ is a robust measure with clinical utility; it can facilitate recognition and assessment of morphing fears The MFQ will allow for further investigations of the prevalence, correlates and treatment outcomes of morphing fears.

Molecular basis of carcinogenicity of tungsten alloy particles.

The tungsten alloy of 91% tungsten, 6% nickel and 3% cobalt (WNC 91-6-3) induces rhabdomyosarcoma when implanted into a rat thigh muscle. To investigate whether this effect is species-specific human HSkMc primary muscle cells were exposed to WNC 91-6-3 particles and responses were compared with those from a rat skeletal muscle cell line (L6-C11). Toxicity was assessed by the adenylate kinase assay and microscopy, DNA damage by the Comet assay. Caspase 3 enzyme activity was measured and oligonucleotide microarrays were used for transcriptional profiling. WNC 91-6-3 particles caused toxicity in cells adjacent to the particles and also increased DNA strand breaks. Inhibition of caspase 3 by WNC 91-6-3 occurred in rat but not in human cells. In both rat and human cells, the transcriptional response to WNC 91-6-3 showed repression of transcripts encoding muscle-specific proteins with induction of glycolysis, hypoxia, stress responses and transcripts associated with DNA damage and cell death. In human cells, genes encoding metallothioneins were also induced, together with genes related to angiogenesis, dysregulation of apoptosis and proliferation consistent with pre-neoplastic changes. An alloy containing iron, WNF 97-2-1, which is non-carcinogenic in vivo in rats, did not show these transcriptional changes in vitro in either species while the corresponding cobalt-containing alloy, WNC 97-2-1 elicited similar responses to WNC 91-6-3. Tungsten alloys containing both nickel and cobalt therefore have the potential to be carcinogenic in man and in vitro assays coupled with transcriptomics can be used to identify alloys, which may lead to tumour formation, by dysregulation of biochemical processes.

Neural correlates of the psychedelic state as determined by fMRI studies with psilocybin.

Psychedelic drugs have a long history of use in healing ceremonies, but despite renewed interest in their therapeutic potential, we continue to know very little about how they work in the brain. Here we used psilocybin, a classic psychedelic found in magic mushrooms, and a task-free functional MRI (fMRI) protocol designed to capture the transition from normal waking consciousness to the psychedelic state. Arterial spin labeling perfusion and blood-oxygen level-dependent (BOLD) fMRI were used to map cerebral blood flow and changes in venous oxygenation before and after intravenous infusions of placebo and psilocybin. Fifteen healthy volunteers were scanned with arterial spin labeling and a separate 15 with BOLD. As predicted, profound changes in consciousness were observed after psilocybin, but surprisingly, only decreases in cerebral blood flow and BOLD signal were seen, and these were maximal in hub regions, such as the thalamus and anterior and posterior cingulate cortex (ACC and PCC). Decreased activity in the ACC/medial prefrontal cortex (mPFC) was a consistent finding and the magnitude of this decrease predicted the intensity of the subjective effects. Based on these results, a seed-based pharmaco-physiological interaction/functional connectivity analysis was performed using a medial prefrontal seed. Psilocybin caused a significant decrease in the positive coupling between the mPFC and PCC. These results strongly imply that the subjective effects of psychedelic drugs are caused by decreased activity and connectivity in the brain's key connector hubs, enabling a state of unconstrained cognition.

Broadband cortical desynchronization underlies the human psychedelic state.

Psychedelic drugs produce profound changes in consciousness, but the underlying neurobiological mechanisms for this remain unclear. Spontaneous and induced oscillatory activity was recorded in healthy human participants with magnetoencephalography after intravenous infusion of psilocybin--prodrug of the nonselective serotonin 2A receptor agonist and classic psychedelic psilocin. Psilocybin reduced spontaneous cortical oscillatory power from 1 to 50 Hz in posterior association cortices, and from 8 to 100 Hz in frontal association cortices. Large decreases in oscillatory power were seen in areas of the default-mode network. Independent component analysis was used to identify a number of resting-state networks, and activity in these was similarly decreased after psilocybin. Psilocybin had no effect on low-level visually induced and motor-induced gamma-band oscillations, suggesting that some basic elements of oscillatory brain activity are relatively preserved during the psychedelic experience. Dynamic causal modeling revealed that posterior cingulate cortex desynchronization can be explained by increased excitability of deep-layer pyramidal neurons, which are known to be rich in 5-HT2A receptors. These findings suggest that the subjective effects of psychedelics result from a desynchronization of ongoing oscillatory rhythms in the cortex, likely triggered by 5-HT2A receptor-mediated excitation of deep pyramidal cells.

Transition and stability of copolymer adsorption morphologies on the surface of carbon nanotubes and implications on their dispersion.

In this study, the adsorption morphologies as well as stability and transitions of a commercial dispersant copolymer (BYK 9076) on the surface of multiwalled carbon nanotubes (MWCNTs) were studied using Fourier transform infrared and UV-vis spectroscopy, dynamic light scattering, and electron microscopy techniques. The results show that the dispersion of carbon nanotubes in ethanol does not increase continuously with increasing copolymer/CNT ratio, which is correlated with the adsorption morphologies of the copolymer on the CNT surface. At a ratio of copolymer/CNT below 0.5, the morphology is random, shifting to a hemimicelle structure at a ratio from 0.5 to 1.0 while at ratios above 1.0, a cylindrical pattern is seen. The hemimicelle morphology is able to prevent the agglomeration of CNTs when the CNT concentration increases to 8.7 mg/mL, while cylindrical morphology is more efficient and stable to provide dispersion of CNTs at higher concentrations of CNTs.

Potentially inappropriate prescribing among older people in the United Kingdom.

BACKGROUND: Potentially inappropriate prescribing (PIP) in older people is associated with increases in morbidity, hospitalisation and mortality. The objective of this study was to estimate the prevalence of and factors associated with PIP, among those aged ≥70 years, in the United Kingdom, using a comprehensive set of prescribing indicators and comparing these to estimates obtained from a truncated set of the same indicators. METHODS: A retrospective cross-sectional study was carried out in the UK Clinical Practice Research Datalink (CPRD), in 2007. Participants included those aged ≥ 70 years, in CPRD. Fifty-two PIP indicators from the Screening Tool of Older Persons Potentially Inappropriate Prescriptions (STOPP) criteria were applied to data on prescribed drugs and clinical diagnoses. Overall prevalence of PIP and prevalence according to individual STOPP criteria were estimated. The relationship between PIP and polypharmacy (≥4 medications), comorbidity, age, and gender was examined. A truncated, subset of 28 STOPP criteria that were used in two previous studies, were further applied to the data to facilitate comparison. RESULTS: Using 52 indicators, the overall prevalence of PIP in the study population (n = 1,019,491) was 29%. The most common examples of PIP were therapeutic duplication (11.9%), followed by use of aspirin with no indication (11.3%) and inappropriate use of proton pump inhibitors (PPIs) (3.7%). PIP was strongly associated with polypharmacy (Odds Ratio 18.2, 95% Confidence Intervals, 18.0-18.4, P < 0.05). PIP was more common in those aged 70-74 years vs. 85 years or more and in males. Application of the smaller subset of the STOPP criteria resulted in a lower PIP prevalence at 14.9% (95% CIs 14.8-14.9%) (n = 151,598). The most common PIP issues identified with this subset were use of PPIs at maximum dose for > 8 weeks, NSAIDs for > 3 months, and use of long-term neuroleptics. CONCLUSIONS: PIP was prevalent in the UK and increased with polypharmacy. Application of the comprehensive set of STOPP criteria allowed more accurate estimation of PIP compared to the subset of criteria used in previous studies. These findings may provide a focus for targeted interventions to reduce PIP.

Thromboelastography in healthy dairy cows.

Thromboelastography is a whole blood-based coagulation assay that can be used to investigate hypocoagulability and hypercoagulability, as seen with thromboembolic diseases and disseminated intravascular coagulation. Numerous coagulopathies due to different causes are reported in cows. The objective was to establish reference intervals for thromboelastography using the TEG 5000 (Haemonetics GmbH, Munich, Germany) with citrated whole blood samples and kaolin activation in dairy cows and to investigate possible thromboelastographic changes between cows in different lactation periods. An additional objective was to test the stability of samples for up to 100h. Sixty blood samples from healthy Holstein-Friesian cows were examined. The samples were allocated to 3 different lactation groups (≤30 d postcalving, 31-99 d postcalving, ≥100 d postcalving). Thromboelastography was performed by using the TEG 5000 analyzer with citrated whole blood samples with kaolin activation. The calculated reference intervals were as follows: reaction time=2.2 to 6.2min, coagulation time=0.8 to 2.0min, angle α=58.2 to 81.8°, maximum amplitude=64.3 to 89.2mm, and clot rigidity=9.2 to 41.2 dyn/cm(2). The 3 different lactation groups showed no significant differences in TEG parameters. No significant difference was seen in samples stored for up to 48h at room temperature, which indicates that delays in processing samples, such as those arising during transit, are not an issue.

Declining genital Warts in young women in england associated with HPV 16/18 vaccination: an ecological study.

BACKGROUND: Diagnoses of genital warts (GW) in genitourinary medicine (GUM) clinics have been increasing in England for many years. In 2008, an HPV immunization program began with a bivalent vaccine (Cervarix). This was expected to markedly reduce infections and disease due to human papillomavirus (HPV) 16/18 but not HPV 6/11 infections or disease. However, from 2009 to 2011 there were decreases in reported diagnoses of GW in young females at GUM clinics. METHODS: Using data from GUM clinics and a sample of general practices (GPs) throughout England, we analyzed rates of GW diagnoses by age, year of diagnosis, and estimated immunization coverage. RESULTS: The overall reduction in GW diagnoses at GUM clinics between 2008 and 2011 was 13.3% among 16- to 19-year-old females, with the greatest decline of 20.8% in 17-year-olds. Declines were positively associated with estimated immunization coverage. A similar pattern was seen in GP diagnoses, but not among older women, and for other GUM consultations. CONCLUSIONS: Several factors might contribute to declines in GW. However, the size and pattern of the declines strongly suggest that we are observing an unexpected, moderately protective effect of HPV 16/18 vaccination against GW.

Vinblastine/prednisolone chemotherapy leads to hematological toxicity in dogs with high-grade or metastatic mast cell tumors.

OBJECTIVE: To determine the myelosuppressive effects/hematological toxicities, other general toxicities, and when these occur during vinblastine/prednisolone chemotherapy in dogs bearing high-grade or metastatic cutaneous/subcutaneous mast cell tumors (MCTs). METHODS: Medical records were retrospectively reviewed between November 1, 2016, and March 1, 2023. Thirty client-owned dogs with histopathologically confirmed cutaneous high-grade MCTs/metastatic subcutaneous MCTs and that subsequently completed a 12-week vinblastine/prednisolone chemotherapy protocol were included. Hematology was assessed before commencing chemotherapy and before each vinblastine treatment. The effect of each treatment upon hematological values was evaluated. Measured outcomes included the type, frequency, and severity of hematological and other more general toxicities. RESULTS: 24 of 30 dogs experienced at least 1 hematological toxicity, 6 experienced gastrointestinal toxicity, and 4 experienced lethargy. The most common toxicity was anemia (15/30 [50%]), with 93.3% (14/15 dogs) classified as Veterinary Cooperative Oncology Group-Common Terminology Criteria for Adverse Events grade I and 6.6% (1/15) classified as grade II. The second most common toxicity was neutropenia (14/30 [46.6%]), with 71.4% (10/14) classified as grade I and 28.6% (4/14) as grade III. The least common hematological toxicity was thrombocytopenia (4/30 [13%]), all grade I. Neutropenia mainly occurred during weeks 2 and 3; however, there was no significant decrease in neutrophil count relative to baseline. Neutrophil count increased and Hct decreased during weeks 6 to 12 of treatment when compared to baseline. No change in platelet count was observed. CLINICAL RELEVANCE: Vinblastine/prednisolone chemotherapy leads to hematological toxicity; however, this was mostly low-grade and did not require major intervention. Vinblastine/prednisolone chemotherapy is well tolerated in dogs bearing high-grade or metastatic MCTs.

Using music to assist language learning in autistic children with minimal verbal language: The MAP feasibility RCT.

LAY ABSTRACT: Research has shown that autistic individuals often have unusually good musical skills and that combining words and music helps autistic individuals to focus on spoken words. This study tests the idea that music will help with early language learning of preschool autistic children. The results show that when caregivers sing words to autistic children, the children pay more attention to the caregiver than when the words are spoken and that they learn word combinations more easily.