Gambling and the Role of Resilience in an International Online Sample of Current and Ex-serving Military Personnel as Compared to the General Population.

Compared to the general population, military personnel are particularly vulnerable to developing gambling problems. The present study examined the presentation of gambling-including gambling frequency, personal thoughts on reducing gambling and recommendations from others to reduce gambling-across these populations. Additionally, the study measured the association between gambling and various psychosocial risk and protective factors-including psychological distress, suicidal ideation, external encouragement to reduce substance use, days out of role, personal wellbeing, resilience, social support and intimate bonds. Data was extracted from the Global Health & Wellbeing Survey, an online self-report survey conducted in Australia, Canada, New Zealand, the United Kingdom and the United States. Of the 10,765 eligible respondents, 394 were military veterans and 337 were active military personnel. Consistent with previous research, a higher proportion of gambling behaviours were observed in both current and ex-serving military samples, compared to the general population. To varying degrees, significant associations were found between the different gambling items and all psychosocial risk and protective factors in the general population sample. However, the military sample yielded only one significant association between gambling frequency and the protective factor 'resilience'. A post hoc stepwise linear regression analysis demonstrated the possible mediating role resilience plays between gambling frequency and other psychosocial risk (psychological distress, and suicidal thoughts and behaviour) and protective factors (personal wellbeing) for the military sample. Given the findings, it is recommended that routine screening tools identifying problem gambling are used within the military, and subsequent resilience focused interventions are offered to at risk personnel.

Diversity in species composition and fungicide resistance profiles in Colletotrichum isolates from apples.

Outbreaks of bitter rot were observed in three commercial apple orchards in Illinois despite best management efforts during the 2018 production season. Three isolates from symptomatic fruit from these orchards and two isolates from an orchard in South Carolina were identified to the species level using morphological tools and calmodulin, glyceraldehyde-3-phosphate dehydrogenase, and beta-tubulin gene sequences. The isolates from Illinois were identified as Colletotrichum siamense of the Colletotrichum gloeosporioides species complex and the ones from South Carolina as Colletotrichum fioriniae and Colletotrichum fructicola of the Colletotrichum acutatum and the C. gloeosporioides species complex, respectively. Two of the three C. siamense isolates from Illinois were resistant to azoxystrobin and thiophanate-methyl as determined in mycelial growth tests in vitro. EC50 values were >100 µg/ml for both fungicides. One isolate was only resistant to azoxystrobin. None of the isolates from South Carolina was resistant to either of the two compounds. All five isolates were sensitive to fludioxonil (EC50 values <0.1 µg/ml), propiconazole (EC50 values ranged from 0.15 to 0.36 µg/ml), and benzovindiflupyr (EC50 values ranged from <0.1 to 0.33 µg/ml). Resistance in C. siamense to azoxystrobin and thiophanate-methyl was confirmed in detached fruit studies using apples treated with label rates of registered product. Resistance to thiophanate-methyl in C. siamense was based on E198A mutation in b-tubulin gene, whereas resistance to azoxystrobin was based on G143A in cytochrome b (CYTB). One isolate resistant to azoxystrobin possessed no amino acid variation in CYTB. This study shows that quinone outside inhibitor fungicide resistance in Colletotrichum from apple has emerged and is being selected for in Illinois apple orchards by current spray strategies. Resistance monitoring may alert growers to potential threats, but the employment of molecular tools based on current knowledge of resistance mechanisms will provide incomplete results.

Neurologic complications after allogeneic hematopoietic stem cell transplantation: risk factors and impact.

Neurologic complications (NCs) may be a significant source of morbidity and mortality after hematopoietic cell transplantation (HCT). We performed a retrospective study of 263 consecutive patients undergoing allogeneic HCT for hematological malignancies to determine the incidence, risk factors and clinical impact of NCs in the first 5 years after HCT. We determined the incidence of central nervous system (CNS) infection, intracranial hemorrhage, ischemic stroke, metabolic encephalopathy, posterior reversal encephalopathy syndrome, seizure and peripheral neuropathy. In all, 50 patients experienced 63 NCs-37 early (⩽day +100), 21 late (day +101 to 2 years) and 5 very late (2 to 5 years). The 1- and 5-year cumulative incidences of all NCs were 15.6% and 19.2%, respectively, and of CNS complication (CNSC; all of the above complications except peripheral neuropathy) were 12.2 and 14.5%. Risk factors for CNSC were age (hazard ratio (HR)=1.06 per year, P=0.0034), development of acute GvHD grade III-IV (HR=2.78, P=0.041), transfusion-dependent thrombocytopenia (HR=3.07, P=0.025) and delayed platelet engraftment (>90th centile; HR=2.77, P=0.043). CNSCs negatively impacted progression-free survival (HR=2.29, P=0.0001), overall survival (HR=2.63, P<0.0001) and non-relapse mortality (HR=8.51, P<0.0001). NCs after HCT are associated with poor outcomes, and usually occur early after HCT.

Small structural changes of the imidazopyridine diacylglycerol acyltransferase 2 (DGAT2) inhibitors produce an improved safety profile.

Small molecule DGAT2 inhibitors have shown promise for the treatment of metabolic diseases in preclinical models. Herein, we report the first toxicological evaluation of imidazopyridine-based DGAT2 inhibitors and show that the arteriopathy associated with imidazopyridine 1 can be mitigated with small structural modifications, and is thus not mechanism related.

Regulation of platelet lifespan in the presence and absence of thrombopoietin signaling.

UNLABELLED: Essentials We examined platelet survival in models of absent or enhanced thrombopoietin (TPO) signaling. Platelet lifespan is normal in transgenic mice with chronically enhanced TPO signaling. Mpl deficiency does not negatively affect platelet lifespan in the absence of thrombocytopenia. We conclude that TPO and its receptor Mpl are dispensable for platelet survival in adult mice. SUMMARY: Background It is well established that thrombopoietin (TPO), acting via its receptor Mpl, is the major cytokine regulator of platelet biogenesis. The primary mechanism by which TPO signaling stimulates thrombopoiesis is via stimulation of Mpl-expressing hematopoietic progenitors; Mpl on megakaryocytes and platelets acts to control the amount of TPO available. TPO could potentially reduce platelet and/or megakaryocyte apoptosis, and therefore increase the platelet count. However, the effect of TPO receptor signaling on platelet survival is unresolved. Methods and results Here, we investigated platelet survival in mouse models of absent or enhanced TPO signaling. In the absence of thrombocytopenia, Mpl deficiency did not negatively influence platelet lifespan, and nor was platelet survival affected in transgenic mice with chronically increased TPO signaling. Conclusions We conclude that TPO and its receptor Mpl are dispensable for platelet survival in adult mice.

High risk HPV testing following treatment for cervical intraepithelial neoplasia.

AIM: To determine the results of combined cytology and high-risk human papilloma virus (HR HPV) tests at 6 and 18 months postcolposcopy treatment at one Irish colposcopy centre. METHODS: All women who attended the centre's colposcopy smear clinic for a co-test 6 months (initial test) posttreatment were included in the audit (n = 251). RESULTS: The results revealed negative HR HPV for 79 % (n = 198) of women tested 6 months after treatment and positive results for 21 % (n = 53). HR HPV testing was more sensitive than cytology and led to early detection of residual disease. No women with negative HR HPV had high-grade cytology. CONCLUSION: HR HPV is more sensitive than cytology for detection of persistent CIN. However, 19 women with positive HR HPV had normal colposcopy with no persistent CIN detected. A national cost-benefit analysis is recommended to determine the value of the second co-test.

Psychological distress and frailty transitions over time in community-dwelling older adults.

OBJECTIVES: Physical health and, in particular, frailty may be associated with psychological factors among older adults. We aimed to investigate the relationships between aspects of psychological distress and progression of frailty over time among older adults. METHODS: We used a longitudinal observational study design with 624 participants aged over 60 years (mean age=72.75, s.d.=7.21, 68% female) completing a baseline comprehensive biopsychosocial geriatric assessment, and 447 returning for a follow-up assessment 2 years later. Aspects of psychological distress, physical health, and frailty were analysed for the purposes of this study. We employed a series of logistic regression analyses to determine psychological predictors of changing states of aspects of frailty over time. RESULTS: With individual components of frailty, neuroticism and age predicted negative transitions of exhaustion and grip strength, respectively, whereas age alone was a predictor of transitions in overall frailty scores based on four components. CONCLUSION: We conclude that neuroticism and age may impact upon physical frailty and its progression over time in an ageing population. These findings may reflect the tendency for those with high levels of neuroticism to endorse negative symptoms, or alternatively, neuroticism may result in exhaustion via worry in an older population. Further research is required to further elucidate this relationship.

Dialectical behaviour therapy (DBT) in the treatment of borderline personality disorder.

Borderline personality disorder (BPD) is a complex disorder that is difficult to treat. However, dialectical behaviour therapy (DBT), developed by Dr. Marsha Linehan in the early 1990s, has emerged as a promising treatment option for those diagnosed with BPD. DBT is a multi-pronged treatment approach delivered normally in outpatient settings over 12 months and requires highly skilled and trained therapists. Many trials have provided evidence to support the use of DBT in the treatment of BPD. However, outcome measures vary and are mostly limited to measurable behavioural outcomes such as incidences of deliberate self-harm or suicidal thoughts. Two recent Cochrane reviews conclude that DBT does benefit those with BPD, but more robust evidence is needed. DBT training for health care professionals also has the potential to shift health care professionals' attitudes from one of therapeutic pessimism to one of optimism.

Quantal and graded stimulation of B lymphocytes as alternative strategies for regulating adaptive immune responses.

Lymphocytes undergo a typical response pattern following stimulation in vivo: they proliferate, differentiate to effector cells, cease dividing and predominantly die, leaving a small proportion of long-lived memory and effector cells. This pattern results from cell-intrinsic processes following activation and the influence of external regulation. Here we apply quantitative methods to study B-cell responses in vitro. Our results reveal that B cells stimulated through two Toll-like receptors (TLRs) require minimal external direction to undergo the basic pattern typical of immunity. Altering the stimulus strength regulates the outcome in a quantal manner by varying the number of cells that participate in the response. In contrast, the T-cell-dependent CD40 activation signal induces a response where division times and differentiation rates vary in relation to stimulus strength. These studies offer insight into how the adaptive antibody response may have evolved from simple autonomous response patterns to the highly regulable state that is now observed in mammals.

Experiences of involuntary admission in an approved mental health centre.

The aim of this qualitative study was to gain an understanding of what it means to have an involuntary hospital admission. A sample of six people who were detained at an approved Irish mental health centre consented to recount their experiences were interviewed. The interview transcripts were analysed using Interpretative Phenomenological Analysis. Three superordinate themes were identified: 'The early days', 'Experiences of treatment' and 'Moving on?'. 'The early days' represented participants' initial feelings and opinions of the experience of coming into the approved centre. 'Experiences of treatment' refers to participants' experiences of medication and relationships with staff. Finally, the theme 'Moving on?' represented participants' views on how they adjusted to involuntary admission. 'Learning the way' was central to the participants' notion of moving on. The findings suggest that the meaning of detention is a varied one that evokes an array of emotional responses for participants and highlights the need for a renewed way of thinking and doing concerning those subject to involuntary.

Reassessment of the pharmacology of Sphingosine-1-phosphate S1P3 receptor ligands using the DiscoveRx PathHunter™ and Ca2+ release functional assays.

BACKGROUND AND PURPOSE: DiscoverRx's PathHunter™ assay measures GPCR agonist potency, via the recruitment of ß-arrestin, independent of the subtype of G(α) protein activated. This assay is frequently used in drug discovery although little is known about the agonist pharmacology generated. Here we have compared agonist potency, efficacy and affinity values obtained in PathHunter™ assays with those from more established radioligand binding and functional techniques. EXPERIMENTAL APPROACH: Using cells expressing the human sphingosine-1-phosphate S1P(3) receptor at four different densities, we compared pharmacological affinity and efficacy values of four structurally distinct ligands - FTY720-P, VPC24191, CYM5442 and the endogenous agonist S1P - obtained from competition binding, functional Ca(2+) release and PathHunter™ assays. KEY RESULTS: The pK(i) values for S1P were significantly different (9.34 ± 0.10 and 8.92 ± 0.15) in clones expressing different receptor levels using the binding assay. In the PathHunter™ and Ca(2+) assays, S1P and CYM5442 were full agonists, FTY720-P was a partial agonist, while the efficacy of VPC24191 could not be detected in PathHunter™ assays. VPC23019, previously described as a S1P(1/3) receptor antagonist, behaved as an S1P(3) receptor partial agonist in the Ca(2+) release assay. CONCLUSIONS AND IMPLICATIONS: Comparison of data from the PathHunter™ assay with binding and functional Ca(2+) assays suggest that PathHunter™ assays measured a different agonist-bound receptor conformation. While this assay has great utility in drug discovery, care must be taken as high-efficacy, low-affinity agonist compounds would not be detected. Therefore highly amplified, more traditional assays are necessary to identify agonists with low efficacy.

Novice performance of ultrasound-guided needle advancement: standard 38-mm transducer vs 25-mm hockey stick transducer.

The optimal method to develop expertise in ultrasound-guided regional anaesthesia is unknown. Studies of laryngoscopic expertise in novices demonstrate that the choice of laryngoscope affects performance. In this study, we aimed to compare the effect of two different linear array transducers (38-mm standard vs 25-mm hockey stick) on novice performance of ultrasound-guided needle advancement. Following randomisation, participants watched a video model of expert performance of ultrasound-guided needle advancement. Recruits performed the modelled task on a turkey breast model. The median (IQR [range]) composite error score was statistically significantly larger for participants in the hockey stick transducer group compared with the standard transducer group; 10.0 (7.3-14.3 [2.5-29.0]) vs 7.5 (4.5-10.0 [2.0-28.0]) respectively, (p = 0.01). This study has demonstrated that performance of ultrasound-guided needle advancement by novice operators after simple video instruction is better (as assessed using a composite error score) with a standard 38-mm transducer than with a 25-mm hockey stick transducer.

Monitoring and documentation of side effects from depot antipsychotic medication: an interdisciplinary audit of practice in a regional mental health service.

This audit reviewed current practice within a rural mental health service area on the monitoring and documentation of side effects of antipsychotic depot medication. A sample of 60 case files, care plans and prescriptions were audited, which is 31% of the total number of service users receiving depot injections in the mental health service region (n= 181). The sample audited had a range of diagnoses, including: schizophrenia, schizoaffective disorder, bipolar affective disorder, depression, alcoholic hallucinosis and autism. The audit results revealed that most service users had an annual documented medical review and a documented prescription. However, only five (8%) case notes examined had documentation recorded describing the condition of the injection site, and alternation of the injection site was recorded in only 28 (47%) case notes. No case notes examined had written consent to commence treatment recorded. In 57 (95%) of case notes, no documentation of recorded information on the depot and on side effects was given. The failure to monitor and record some blood tests was partly attributed to a lack of clarity regarding whose responsibility it was. A standardized checklist has been developed as a result of the audit and this will be introduced by all teams across the service.

Automated and semi-automated cell tracking: addressing portability challenges.

Cell tracking is a key task in the high-throughput quantitative study of important biological processes, such as immune system regulation and neurogenesis. Variability in cell density and dynamics in different videos, hampers portability of existing trackers across videos. We address these potability challenges in order to develop a portable cell tracking algorithm. Our algorithm can handle noise in cell segmentation as well as divisions and deaths of cells. We also propose a parameter-free variation of our tracker. In the tracker, we employ a novel method for recovering the distribution of cell displacements. Further, we present a mathematically justified procedure for determining the gating distance in relation to tracking performance. For the range of real videos tested, our tracker correctly recovers on average 96% of cell moves, and outperforms an advanced probabilistic tracker when the cell detection quality is high. The scalability of our tracker was tested on synthetic videos with up to 200 cells per frame. For more challenging tracking conditions, we propose a novel semi-automated framework that can increase the ratio of correctly recovered tracks by 12%, through selective manual inspection of only 10% of all frames in a video.

Patient centric identification and association.

Increased technological complexity of medical devices and systems coupled with increased workloads and reduced staffing, have created difficulties and discontinuities in the management of patient information. These issues have directly impacted and contributed to a rise in equipment-related errors, patient dissatisfaction, a potential for patient injury and resulting overall increased concern for patient safety. In response these concerns a variety of new devices, systems and applications have been developed to share information, provide cross checks along with verified delivery of critical information to the point of care. These applications include biomedical information systems, medication administration, sample collection, and electronic medical records. The deployment of these new integrated and networked devices, systems and applications are dependent on an accurate and consistent patient identification and association methodology which dynamically manages the relationship between patients, staff and equipment. Since the association information is common to many applications and utilizes a variety of technologies, (i.e. active and passive radio frequency identification (RFID), barcodes, etc.) an institutional approach is necessary to mange these processes in a consistent manor utilizing a common set of identification hardware. Implementation of a "Patient Centric Identification and Association Platform" represents a significant advance in the management of clinical patient information. The implementation of a Biomedical Device Information Network at Memorial Sloan-Kettering Cancer Center (MSKCC) integrates the identification and association of patients with devices and care providers and provides the methodologies to manage alarms, providing the ability to filter low priority or nuisance alarms. This implementation enables critical information to be distributed directly to care providers utilizing dedicated communications devices. Patient Centric Identification and Association is the enabling technology providing precise identification and association establishing an enhanced environment of care, increased patient safety, and a clear proactive response to the regulatory requirements of the Joint Commission (JCAHO) national patient safety initiatives.

Knowledge and attitudes of mental health professionals in Ireland to the concept of recovery in mental health: a questionnaire survey.

Recovery is the model of care presently advocated for mental health services internationally. The aim of this study was to examine the knowledge and attitudes of mental health professionals to the concept of recovery in mental health. A descriptive survey approach was adopted, and 153 health care professionals (nurses, doctors, social workers, occupational therapists and psychologists) completed an adapted version of the Recovery Knowledge Inventory. The respondents indicated their positive approach to the adoption of recovery as an approach to care in the delivery of mental health services. However, respondents were less comfortable in encouraging healthy risk taking with service users. This finding is important because therapeutic risk taking and hope are essential aspects in the creation of a care environment that promotes recovery. Respondents were also less familiar with the non-linearity of the recovery process and placed greater emphasis on symptom management and compliance with treatment. Multidisciplinary mental health care teams need to examine their attitudes and approach to a recovery model of care. The challenge for the present and into the future is to strive to equip professionals with the necessary skills in the form of information and training.

Developing practice in cancer rehabilitation.

This module explores the concept of rehabilitation and supportive care in a cancer context. It examines policy and practice that inform rehabilitation in cancer care in England and considers how rehabilitation and supportive care issues can be addressed in clinical practice.

A model of immune regulation as a consequence of randomized lymphocyte division and death times.

The magnitude of an adaptive immune response is controlled by the interplay of lymphocyte quiescence, proliferation, and apoptosis. How lymphocytes integrate receptor-mediated signals influencing these cell fates is a fundamental question for understanding this complex system. We examined how lymphocytes interleave times to divide and die to develop a mathematical model of lymphocyte growth regulation. This model provides a powerful method for fitting and analyzing fluorescent division tracking data and reveals how summing receptor-mediated kinetic changes can modify the immune response progressively from rapid tolerance induction to strong immunity. An important consequence of our results is that intrinsic variability in otherwise identical cells, usually dismissed as noise, may have evolved to be an essential feature of immune regulation.

Neuodevelopmental outcomes for children transplanted under the age of 3 years.

UNLABELLED: Our previous investigations on neurodevelopmental outcomes for intestinal transplanted infants revealed that while some children were able to achieve a normal developmental outcomes, most children suffered from significant motor delays and several experienced severe cognitive delays. In our current investigation, we were especially interested in children who are transplanted before the age of 3 years because the impact of the chronic illness and nutrition impairment on the infant's developing brain may be more severe than those children who receive a liver transplant. METHODS: We evaluated 34 infants using the Bayley Scales of Infant Development. Twenty-seven children received a liver/intestine or multivisceral transplant and seven received a liver transplant. RESULTS: Comparison of the two groups revealed that children receiving an intestine/multivisceral transplant have much poorer outcomes. Seventy-four percent of these children were significantly delayed mentally compared to only 57.14% of the liver transplant infants. Furthermore, 42.86% of the liver-transplanted infants were actually functioning in the normal range posttransplant. The intestinal/multivisceral transplant infants' motor development shows the most striking difference, with 96.3% being severely delayed as compared to liver transplant infants in whom only 71% experienced serious delays. The neurodevelopmental impact of organ failure and transplant before the age of 3 years may depending on the type of organ transplant. Our study found that it may be more likely to expect a good outcome for liver transplant patients than for intestinal and multivisceral transplanted infants. This difference maybe due to the overall severity of the disease and the possible impact of nutritional deficits early in infancy.

Neurodevelopmental outcomes of infant multivisceral transplant recipients: a longitudinal study.

UNLABELLED: This longitudinal investigation compares cognitive and physical capabilities of transplant recipients, both before and after receiving an intestinal transplant. METHODS: Using the Bayley Scales of Infant Development, we conducted pretransplant and posttransplant assessments on nine children (4 males, 5 females) who received either an isolated intestine, combined intestine and liver, or multivisceral transplants, with a mean age at transplant of 18 months (range 8-29) and a mean time posttransplant of 2 months (range 1-4 months). RESULTS: Scores on the Mental Developmental Index reflected that a majority (55.6%) of patients who scored in the significantly delayed range prior to transplant remained in the significantly delayed classification after receiving a transplant. In addition, 33.3% showed a decrease in their mental classification; either from "mildly delayed" to "significantly delayed" or from "within normal limits" to "mildly delayed". Results on the Motor Developmental Index demonstrated that 78% of recipients had significant delays both before and after receiving a transplant, while 11.1% fell one standard deviation after transplantation. We found that the majority of children who experience developmental delays prior to transplant are still experiencing delays when they are discharged from inpatient care. In addition, those children receiving multivisceral transplantations, as opposed to an isolated bowel, may be at a much greater risk of developing and retaining both cognitive and physical delays. Early neurodevelopmental evaluations of these patients is essential for early parental education and compliance with early intervention services to maximize potential recovery and ability to obtain normal development.