Discrimination of constructed air samples using multivariate analysis of full scan membrane introduction mass spectrometry (MIMS) data.

RATIONALE: Volatile and semi-volatile organic compounds (S/VOCs) are important atmospheric pollutants affecting both human and environmental health. They are directly measured as an unresolved mixture using membrane introduction mass spectrometry (MIMS). We apply chemometric techniques to discriminate, classify, and apportion air samples from a variety of sources. METHODS: Full scan mass spectra of lab-constructed air samples were obtained using a polydimethylsiloxane membrane interface and an electron ionization ion trap mass spectrometer. Normalized full scan spectra were analyzed using principal component analysis (PCA), cluster analysis, and k-nearest neighbours (kNN) for sample discrimination and classification. Multivariate curve resolution (MCR) was used to extract pure component contributions. Similar techniques were applied to VOC mixtures sampled from different woodsmoke emissions and from the headspace above aqueous hydrocarbon solutions. RESULTS: PCA successfully discriminated 32 constructed VOC mixtures from nearly 300 air samples, with cluster analysis showing similar results. Further, kNN classification (k = 1) correctly classified all but one test set sample, and MCR successfully identified the pure compounds used to construct the VOC mixtures. Real-world samples resulting from the combustion of different wood species and those associated with water contaminated with different commercial hydrocarbon products were similarly discriminated by PCA. CONCLUSIONS: Chemometric techniques have been evaluated using full scan MIMS spectra with a series of VOC mixtures of known composition containing known compounds, and successfully applied to samples with known sources, but unknown molecular composition. These techniques have application to source identification and apportionment in real-world environmental samples impacted by atmospheric pollutants.

Who's challenging who training for staff empathy towards adults with challenging behaviour: cluster randomised controlled trial.

BACKGROUND: One in five adults with intellectual disabilities (ID) known to services display challenging behaviours (CBs), and these individuals are at risk for restrictive practices and poor care. Staff attitudes may contribute to the development and/or maintenance of CBs. We investigated the effectiveness of co-produced Who's Challenging Who? training delivered by people with ID to staff. METHOD: This study involved a cluster randomised controlled trial (RCT) of Who's Challenging Who? training with follow-up at six and 20 weeks post-randomisation. PARTICIPANTS: two staff from each of 118 residential care settings for adults with ID at least one of whom displayed aggressive CB. PRIMARY OUTCOME: Self-reported Staff Empathy for people with Challenging Behaviour Questionnaire. ANALYSIS: intention to treat of all randomised settings. ISCRTN registration: ISRCTN53763600. RESULTS: 118 residential settings (including 236 staff) were randomised to either receive training (59 settings) or to receive training after a delay (59 settings). The primary analysis included data from 121 staff in 76 settings (51% of staff, 64% of settings). The adjusted mean difference on the transformed (cubed) Staff Empathy for people with Challenging Behaviour Questionnaire score at the primary end point was 1073.2 (95% CI: -938.1 to 3084.5, P = 0.296) in favour of the intervention group (effect size Cohen's d = .19). CONCLUSIONS: This is the first large-scale RCT of a co-produced training course delivered by people with ID. Findings indicated a small positive (but statistically non-significant) effect on increased staff empathy at 20 weeks, and small to moderate effects for staff reported secondary outcomes in favour of the intervention group.

Endodontic regeneration and tooth revitalization in immature infected sheep teeth.

AIM: To examine the response of immature sheep teeth with infected root canal systems to a commonly used pulp regeneration/revitalization protocol. METHODOLOGY: Immature mandibular right first incisors in four sheep were mechanically exposed and the pulps infected. The mandibular left first incisors remained intact as controls. Five weeks later, the experimental root canals were chemo-mechanically cleaned and dressed with a triple-antibiotic paste for 4 weeks, before bleeding was induced inside the canal by mechanically irritating the periapical tissues. A collagen dressing was packed coronally onto the blood clot and the canal orifice sealed with mineral trioxide aggregate and glass ionomer cement. Six months later, the mandibles were collected and the teeth with associated periapical tissues were analysed radiographically, with CT scanning, and by histology. The changes in root length, dentine thickness in the apical third (mesially and distally), and apical diameter were analysed using Student's t-test. RESULTS: Radiographs revealed significant increases in root length, root wall thickness and narrowing of the apical diameter of the canals after treatment (P < 0.05), with no significant differences in root diameters found between the experimental and the control teeth (P > 0.05) on both radiographic and CT results. Root maturation and thickening of the walls due to hard tissue deposition was confirmed by histology in all experimental teeth. Hard tissues in the apical portion of the root were more developed than in the coronal portion. CONCLUSION: Endodontic regeneration and tooth revitalization procedures in immature infected sheep teeth showed positive outcomes with similar increases in root length and development to the control teeth.

Treatment of two patients with generalized pustular psoriasis with the interleukin-1ß inhibitor gevokizumab.

Generalized pustular psoriasis (GPP) is a severe, potentially life-threatening inflammatory dermatosis, which is traditionally difficult to manage. Recent evidence suggests that interleukin (IL)-1 plays a central role in the disease pathogenesis, and thus makes the use of IL-1 inhibitors potentially effective. Two patients with severe, recalcitrant GPP were enrolled in an open-label, expanded access study to receive a new IL-1ß inhibitor, gevokizumab. The two patients had a respective 79% and 65% reduction in GPP area and severity index scores at weeks 4 and 12, with some improvements in quality-of-life instruments. There were no significant adverse events related to the study medication, although one patient developed an abscess in a haematoma secondary to an injury. Both patients showed substantial initial clinical response to gevokizumab, with no significant laboratory abnormalities noted. These cases illustrate the growing need for targeted, efficacious therapies for this severe, debilitating disease. Prospective randomized control studies are required to further assess the safety and efficacy of IL-1ß inhibitors for the treatment of GPP.

A new cytotype of the African pygmy mouse Mus minutoides in Eastern Africa. Implications for the evolution of sex-autosome translocations.

The African pygmy mice (genus Mus, subgenus Nannomys) are recognized for their highly conserved morphology but extensive chromosomal diversity, particularly involving sex-autosome translocations, one of the rarest chromosomal rearrangements among mammals. It has been shown that in the absence of unambiguous diagnostic morphological traits, sex-autosome translocations offer accurate taxonomic markers. For example, in Mus minutoides, irrespective of the diploid number (which ranges from 2n = 18 to 34), all specimens possess the sex-autosome translocations (X.1) and (Y.1) that are unique to this species. In this study, we describe a new cytotype that challenges this view. Males are characterized by the translocation (Y.1) only, while females carry no sex-autosome translocation, the X chromosome being acrocentric. Hence, although sex-autosome translocations (X.1) and (Y.1) are still diagnostic when one or both are present, their absence does not rule out M. minutoides. This cytotype has a large distribution, with specimens found in Tanzania and in the eastern part of South Africa. The nonpervasive distribution of Rb(X.1) provides an opportunity to investigate different evolutionary scenarios of sex-autosome translocations using a phylogenetic framework and the distribution of telomeric repeats. The results tend to support a scenario involving a reversal event, i.e., fusion then fission of Rb(X.1), and highlighted the existence of a new X1X1X2X2/X1X2Y sex chromosome system, confirming the remarkable diversity of neo-sex chromosomes and sex determination systems in the African pygmy mice.

Missed rifampicin and isoniazid resistance by commercial molecular assays.

Drug-resistant tuberculosis (TB) has poor outcomes unless resistance is detected early, ideally by commercially available molecular tests. We present a case of occult multidrug-resistant TB where both rifampicin and isoniazid resistance were missed by molecular testing and were only identified by phenotypic testing.

A prospective bacterial whole-genome-sequencing-based surveillance programme for comprehensive early detection of healthcare-associated infection transmission in paediatric oncology patients.

BACKGROUND: Bacterial whole-genome sequencing (WGS) and determination of genetic relatedness is an important tool for investigation of epidemiologically suspected outbreaks. AIM: This prospective cohort study evaluated a comprehensive, prospective bacterial WGS-based surveillance programme for early detection of transmission of most bacterial pathogens among patients at a paediatric oncology hospital. METHODS: Cultured bacterial isolates from clinical diagnostic specimens collected prospectively from both inpatient and outpatient encounters between January 2019 and December 2021 underwent routine WGS and core genome multi-locus sequence typing to determine isolates' relatedness. Previously collected isolates from January to December 2018 were retrospectively analysed for identification of prior or ongoing transmission. Multi-patient clusters were investigated to identify potential transmission events based on temporal and spatial epidemiological links and interventions were introduced. FINDINGS: A total of 1497 bacterial isolates from 1025 patients underwent WGS. A total of 259 genetically related clusters were detected, of which 18 (6.9%) multi-patient clusters involving 38 (3.7%) patients were identified. Sixteen clusters involved two patients each, and two clusters involved three patients. Following investigation, epidemiologically plausible transmission links were identified in five (27.8%) multi-patient clusters. None of the multi-patient clusters were suspected by conventional epidemiological surveillance. CONCLUSION: Bacterial WGS-based surveillance for early detection of hospital transmission detected several limited multi-patient clusters that were unrecognized by conventional epidemiological methods. Genomic surveillance helped efficiently focus interventions while reducing unnecessary investigations.

Behavior Sequence Analysis of Victims' Accounts of Intimate Partner Violence.

Intimate partner violence (IPV) relates not only to physical forms of abuse, but also psychological, emotional, economic, and financial controlling behaviors. IPV is a dynamic, complex phenomenon that occurs over a relatively long period of time. While several measures of IPV exist, a method that can track the progression and escalation of such behaviors in relationships could offer more understanding and highlight key intervention points for individuals in such relationships. Behavior Sequence Analysis is used in the current research to map the chain and progression of behaviors in multiple real-world cases of IPV. Results indicate clear sequential clusters of behaviors such as physical and psychological abuse, and coercive controlling behaviors such as gaslighting, restricting movement, and removing freedoms. Overall, this research stands as a foundation framework to build a greater understanding of the processes and pathways of IPV, and offers workers in the field a novel method to assist with interviewing and intervening in such cases.

Hydrochemical characterization, spatial distribution, and geochemical controls on arsenic and boron in waters from arid Arica and Parinacota, northern Chile.

The livelihood of inhabitants from rural agricultural valleys in the arid Arica and Parinacota Region, northernmost Chile, strongly depends on water from high altitude rainfall and runoff to lower elevation areas. However, elevated arsenic, boron, and other potentially harmful elements compromise water quality, especially in rural areas. Samples (n = 90) of surface, underground, cold, geothermal springs, and treated and raw tap water were studied to assess water quality and to determine the main geochemical controls on water composition, origin, and geochemical evolution along dominant flowpaths. Water from major river basins across the region (Lluta, San Jose, Codpa-Chaca, Camarones and Altiplanicas) were collected for hydrogeochemical analysis of a suite of major and trace elements, δD and δ18O. Our new dataset was supplemented by hydrochemical data (n > 1500 data points) from secondary sources. Results show that 72% of the collected samples had As >10 µg/L (WHO drinking water provisional guideline) and affected 44% of the studied waters used for drinking (n = 32). Based on Chilean irrigation guidelines, elevated salinity (EC > 0.75 mS/cm) affected 80% of sampled waters, which were also impacted by high B (89% > 0.75 mg/L), and As (31% > 50 µg/L). Water composition was strongly controlled by geothermal water and freshwater mixing in high altitude areas. Magnitude and fate of As and B concentration was determined by the geothermal input type. Highest As (~21 mg/L) was associated with circum-neutral Na-Cl waters in Camarones basin, while lower As (~5 mg/L) with acid SO4 waters in Lluta basin. Additionally, evaporative concentration and sediment-water interactions were shown to control the level of As in surface and groundwaters downstream. This works provides a comprehensive analysis and a conceptual model of geochemical controls on regional water compositions, contributing to better understanding the geochemical processes underpinning the water quality challenges in northern Chile.

Beyond Diffusion Tensor MRI Methods for Improved Characterization of the Brain after Ischemic Stroke: A Review.

Ischemic stroke is a worldwide problem, with 15 million people experiencing a stroke annually. MR imaging is a valuable tool for understanding and assessing brain changes after stroke and predicting recovery. Of particular interest is the use of diffusion MR imaging in the nonacute stage 1-30 days poststroke. Thousands of articles have been published on the use of diffusion MR imaging in stroke, including several recent articles reviewing the use of DTI for stroke. The goal of this work was to survey and put into context the recent use of diffusion MR imaging methods beyond DTI, including diffusional kurtosis, generalized fractional anisotropy, spherical harmonics methods, and neurite orientation and dispersion models, in patients poststroke. Early studies report that these types of beyond-DTI methods outperform DTI metrics either in being more sensitive to poststroke changes or by better predicting outcome motor scores. More and larger studies are needed to confirm the improved prediction of stroke recovery with the beyond-DTI methods.

The effect of pre-analytical variables on downstream application and data analysis of human endometrial biopsies.

STUDY QUESTION: What are the effects of pre-analytical variables on the downstream analysis of patient-derived endometrial biopsies? SUMMARY ANSWER: There are distinct differences in the protein levels of the master regulator of oxygen homeostasis, hypoxia-inducible factor-1-alpha (HIF1α), and the protein and mRNA levels of three related genes, carbonic anhydrase 9 (CA9), vascular endothelial growth factor A (VEGFA) and progesterone receptor (PR) in human endometrial biopsies, depending on the pre-analytical variables: disease status (cancer vs benign), timing of biopsy (pre- vs post-hysterectomy) and type of biopsy (pipelle vs full-thickness). WHAT IS KNOWN ALREADY: Patient-derived biopsies are vital to endometrial research, but pre-analytical variables relating to their collection may affect downstream analysis, as is evident in other tissues. STUDY DESIGN SIZE DURATION: A prospective observational study including patients undergoing hysterectomy for endometrial cancer (EC) or benign indications was conducted at a large tertiary gynaecological unit in the UK. Endometrial biopsies were obtained at different time points (pre- or post-hysterectomy) using either a pipelle endometrial sampler or as a full-thickness wedge biopsy. PARTICIPANTS/MATERIALS SETTING METHODS: The changes in HIF1α, CA9, VEGFA and PR protein levels were measured by semi-quantitative analysis of immunostaining, and the expression levels of three genes (CA9, VEGFA and PR) were investigated by quantitative real-time PCR, in endometrial biopsies from 43 patients undergoing hysterectomy for EC (n = 22) or benign gynaecological indications (n = 21). MAIN RESULTS AND THE ROLE OF CHANCE: An increase in HIF1α immunostaining was observed in EC versus benign endometrium (functionalis glands) obtained pre-hysterectomy (P < 0.001). An increase in CA9 immunostaining was observed in EC versus benign endometrial functionalis glands at both pre- and post-hysterectomy time points (P = 0.03 and P = 0.003, respectively). Compared with benign endometrial pipelle samples, EC samples demonstrated increased mRNA expression of CA9 (pre-hysterectomy P < 0.001, post-hysterectomy P = 0.008) and VEGFA (pre-hysterectomy P = 0.004, post-hysterectomy P = 0.002). In benign uteri, HIF1α immunoscores (functionalis glands, P = 0.03 and stroma, P = 0.009), VEGFA immunoscores (functionalis glands, P = 0.03 and stroma, P = 0.01) and VEGFA mRNA levels (P = 0.008) were increased in matched post-hysterectomy versus pre-hysterectomy samples. Similarly, in EC, an increase in VEGFA immunoscores (epithelial and stromal) and VEGFA mRNA expression was observed in the matched post-hysterectomy versus pre-hysterectomy biopsies (P = 0.008, P = 0.004 and P = 0.018, respectively). Full-thickness benign post-hysterectomy endometrial biopsies displayed increased VEGFA (P = 0.011) and PR (P = 0.006) mRNA expression compared with time-matched pipelle biopsies. LARGE SCALE DATA: N/A. LIMITATIONS REASONS FOR CAUTION: This descriptive study explores the effect of pre-analytical variables on the expression of four proteins and three hypoxia-related genes in a limited number of endometrial biopsies from patients with EC and benign controls. Due to the small number, it was not possible to investigate other potential variables such as menstrual cycle phase, region-specific differences within the endometrium, grade and stage of cancer, and surgical technicalities. WIDER IMPLICATIONS OF THE FINDINGS: Careful consideration of the effects of these pre-analytical variables is essential when interpreting data relating to human endometrial biopsies. A standardized approach to endometrial tissue collection is essential to ensure accurate and clinically transferrable data. STUDY FUNDING/COMPETING INTERESTS: The authors have no conflicts of interest to declare. The work included in this manuscript was funded by Wellbeing of Women project grants RG1073 and RG2137 (D.K.H.), Wellbeing of Women Entry-Level Scholarship ELS706 and Medical Research Council MR/V007238/1 (A.M./D.K.H.), Liverpool Women's Hospital Cancer Charity (M.A.) and University of Liverpool (L.B., L.R. and E.N.).

The pharmacokinetics and safety of desvenlafaxine in subjects with chronic renal impairment.

BACKGROUND: Desvenlafaxine (administered as desvenlafaxine succinate), the major active metabolite of venlafaxine, is a new serotonin-norepinephrine reuptake inhibitor (SNRI) approved for the treatment of major depressive disorder (MDD). OBJECTIVE: To assess the pharmacokinetics, safety, and tolerability of desvenlafaxine in healthy volunteers vs. those with renal impairment. MATERIALS AND METHODS: A single, oral, 100 mg dose of desvenlafaxine was administered to healthy subjects (n = 8) and subjects with mild (n = 9), moderate (n = 9), or severe (n = 7) renal impairment (24-h creatinine clearance, ml/min: 50 - 80, 30 - 50, or < 30 ml/min, respectively) or end-stage renal disease (ESRD; on dialysis.

A randomised controlled masked clinical trial of two treatments for osteoarthritis in dogs.

The product 4CYTE™ Canine (Interpath Pty Ltd., Ballarat, Victoria, Australia) contains four active ingredients: three marine-derived ingredients and Epiitalis®, which is extracted from the seed of the plant Biota orientalis. Carprofen is a non-steroidal anti-inflammatory drug (NSAID) licensed for the treatment of osteoarthritis in dogs and is the active ingredient in several licensed products. This study aimed to compare the efficacy of 4CYTE Canine with carprofen for the treatment of pain from osteoarthritis. The trial was a randomised, masked, parallel group trial in dogs with naturally occurring osteoarthritis. Sixty-nine dogs with body weight of between 10 and 50 kg were enrolled in the study, of which 66 (95.7%) completed the study. The 4CYTE Canine was administered at 60 mg active/kg daily and carprofen at 2-4 mg/kg daily, with a loading dose of up to 4 mg/kg on the first day. The trial duration was 28 days. The primary outcome was defined as improvement in Owner Lameness Score at Day 28 compared with Day 0. Other outcomes measured included Veterinary Lameness Scores and the Owner Mobility Scores. At Day 28, 14 of 29 (48.3%) dogs that received 4CYTE Canine and 13 of 37 (35.1%) dogs that received carprofen had improved. The 4CYTE Canine was found to be non-inferior to carprofen at Day 14 for the Owner Mobility Score and at Day 28 for all three outcomes. This response pattern suggests that improvement in response to 4CYTE Canine continued between Days 14 and 28. These results support the conclusion that 4CYTE Canine is not inferior to carprofen by end-point clinical efficacy.

How decision-making about euthanasia for animals is taught to Australasian veterinary students.

This study set out to explore how euthanasia decision-making for animals was taught to students in eight Australasian veterinary schools. A questionnaire-style interview guide was used by a representative at each university to interview educators. Educators were interviewed about their teaching of euthanasia decision-making for four categories of animals: livestock, equine, companion and avian/wildlife. Using thematic analysis, the terms provided by participants to describe how (mode of teaching) and what (specific content) they taught to students were categorised. Information about content was categorised into human-centred factors that influence decision-making, and animal-based indicators used to directly inform decision-making. All eight representatives reported some teaching relevant to euthanasia decision-making at their university for livestock, companion animal and avian/wildlife. One representative reported no such teaching for equid animals at their university. Observation of a euthanasia case was rarely reported as a teaching method. Five universities reported multiple modes of teaching relevant information, while two universities made use of modalities that could be described as opportunistic teaching (e.g., 'Discussion of clinical cases'). Factors taught at most universities included financial considerations, and that it is the owner's decision to make, while animal-based indicators taught included QoL/animal welfare, prognosis and behaviour change. Overall, most universities used a variety of methods to cover relevant material, usually including lectures and several other approaches for all animal types. However, because two universities relied on presentation of clinical cases, not all students at these veterinary schools will be exposed to make, or assist in making, euthanasia decisions.

Perceptions of registered nurses in four state health insititutions on continuing formal education.

This study investigated registered nurses in four selected state health institutions' perceptions with regard to continuing formal education. The relevance of continuing formal education is being emphasised globally by the increasing quest for quality assurance and quality management systems within an ethos of continuous improvement. According to Tlholoe (2006:5), it is important to be committed to continual learning, as people's knowledge become less relevant because skills gained early in a career are insufficient to avoid costly mistakes made through ignorance. Continuing formal education in nursing is a key element to the maintenance of quality in health care delivery. The study described: registered nurses' views on continuing formal education. Registered nurses' perceived barriers to continuing formal education. A quantitative descriptive survey design was chosen using a questionnaire for data collection. The sample consisted of 40 registered nurses working at four state health institutions in the Western Cape Province, South Africa. Convenience sampling was selected to include registered nurses who were on duty on the days during which the researcher visited the health institutions to distribute the questionnaires. The questionnaire contained mainly closed-ended and a few open-ended questions. Content validity of the instrument was ensured by doing a thorough literature review before construction of items and a pretest. Reliability was established by the pretest and providing the same information to all respondents before completion of the questionnaires. The ethical considerations of informed consent, anonymity and confidentiality were adhered to and consent to conduct the study was obtained from relevant authorities. Descriptive statistics, based on calculations using the Microsoft (MS) Excel (for Windows 2000) programme, were used to summarise and describe the research results. The research results indicated that most registered nurses perceive continuing formal education as beneficial to their personal and professional growth and that it could lead towards improving the quality of patient/client care, but barriers exist which prevent or deter them from undertaking continuing formal education programmes. The main structural barriers included lack of funding and lack of coherent staff development planning and physical barriers including job and family responsibilities.

Discrimination and geo-spatial mapping of atmospheric VOC sources using full scan direct mass spectral data collected from a moving vehicle.

Volatile and semi-volatile organic compounds (S/VOCs) are ubiquitous in the environment, come from a wide variety of anthropogenic and biogenic sources, and are important determinants of environmental and human health due to their impacts on air quality. They can be continuously measured by direct mass spectrometry techniques without chromatographic separation by membrane introduction mass spectrometry (MIMS) and proton-transfer reaction time-of-flight mass spectrometry (PTR-ToF-MS). We report the operation of these instruments in a moving vehicle, producing full scan mass spectral data to fingerprint ambient S/VOC mixtures with high temporal and spatial resolution. We describe two field campaigns in which chemometric techniques are applied to the full scan MIMS and PTR-ToF-MS data collected with a mobile mass spectrometry lab. Principal Component Analysis (PCA) has been successfully employed in a supervised analysis to discriminate VOC samples collected near known VOC sources including internal combustion engines, sawmill operations, composting facilities, and pulp mills. A Gaussian mixture model and a density-based spatial clustering of application with noise (DBSCAN) algorithm have been used to identify sample clusters within the full time series dataset collected and we present geospatial maps to visualize the distribution of VOC sources measured by PTR-ToF-MS.

How management of grief associated with ending the life of an animal is taught to Australasian veterinary students.

OBJECTIVE: Veterinarians have an important role in supporting and understanding their clients' grief. Veterinary schools have a duty to teach students how best to manage grief - both that of the students/future veterinarians and the clients. This study explores how grief management, associated with ending the life of an animal, was taught to students in eight Australasian veterinary schools. METHODS: A questionnaire-style interview guide was used by a representative at each university to conduct structured interviews with educators in a snowball sampling approach. Educators were interviewed about the teaching of grief management for four categories of animals: livestock, equine, companion and avian/wildlife. The terms used by participants to describe what they taught were grouped into common themes. Teaching was defined by individual participants and included structured and unstructured approaches. The stage in the degree (preclinical or clinical years) that grief management was taught in the veterinary curriculum and by whom (e.g. clinicians or psychologists) is also described. RESULTS: Grief management was taught more in preclinical than clinical years. However, due to how grief was characterised, much of this teaching was general 'nonspecific' teaching that included all categories of animals. Client grief was taught more generically, whereas, grief of veterinarians was taught using specific examples given by clinicians. CONCLUSION: A more robust end-of-life (EoL) management curriculum that includes all aspects of grief management is likely to increase job satisfaction, client happiness and professional satisfaction.