Exploring suicidal behaviours by probation clients-a qualitative near-lethal study.

Background: Existing research emphasizes that offenders serving community based sentences are at an increased risk of suicide compared with the general population, however, there is little understanding about the causes of this risk. The aim of the current research was to understand how to support probation clients and prevent suicide, by exploring the experiences of probation clients who carried out near-lethal suicide attempts whilst under probation supervision. Methods: In-depth interviews were carried out with seven probation clients who made near-lethal suicide attempts whilst serving a probation sentence. Data were analysed using Interpretative Phenomenological Analysis. Results: Participants recounted negative experiences which they perceived to be linked to their suicidal feelings and behaviours, such as experiencing bereavements, perceived loss of control over their mental state or situation, and difficulties relating to stages of their probation sentence. Participants expressed severe difficulties with trusting authorities, making disclosure of suicidal feelings problematic. However, participants emphasized the role that purposeful and meaningful activity can play in suicide prevention. Conclusions: Suicide prevention strategies must be tailored to the needs of probation clients across the UK. Mandatory training for probation staff is recommended to help reduce suicides, and support from external agencies should be sought where possible.

Pseudomonas aeruginosa Induced Airway Epithelial Injury Drives Fibroblast Activation: A Mechanism in Chronic Lung Allograft Dysfunction.

Bacterial infections after lung transplantation cause airway epithelial injury and are associated with an increased risk of developing bronchiolitis obliterans syndrome. The damaged epithelium is a source of alarmins that activate the innate immune system, yet their ability to activate fibroblasts in the development of bronchiolitis obliterans syndrome has not been evaluated. Two epithelial alarmins were measured longitudinally in bronchoalveolar lavages from lung transplant recipients who developed bronchiolitis obliterans syndrome and were compared to stable controls. In addition, conditioned media from human airway epithelial cells infected with Pseudomonas aeruginosa was applied to lung fibroblasts and inflammatory responses were determined. Interleukin-1 alpha (IL-1α) was increased in bronchoalveolar lavage of lung transplant recipients growing P. aeruginosa (11.5 [5.4-21.8] vs. 2.8 [0.9-9.4] pg/mL, p < 0.01) and was significantly elevated within 3 months of developing bronchiolitis obliterans syndrome (8.3 [1.4-25.1] vs. 3.6 [0.6-17.1] pg/mL, p < 0.01), whereas high mobility group protein B1 remained unchanged. IL-1α positively correlated with elevated bronchoalveolar lavage IL-8 levels (r(2)  = 0.6095, p < 0.0001) and neutrophil percentage (r(2)  = 0.25, p = 0.01). Conditioned media from P. aeruginosa infected epithelial cells induced a potent pro-inflammatory phenotype in fibroblasts via an IL-1α/IL-1R-dependent signaling pathway. In conclusion, we propose that IL-1α may be a novel therapeutic target to limit Pseudomonas associated allograft injury after lung transplantation.

Impact of age and medical comorbidity on adjuvant treatment outcomes for stage III colon cancer: a pooled analysis of individual patient data from four randomized, controlled trials.

BACKGROUND: Adjuvant oxaliplatin plus capecitabine or leucovorin/5-fluorouracil (LV/5-FU) (XELOX/FOLFOX) is the standard of care for stage III colon cancer (CC); however, there is disagreement regarding oxaliplatin benefit in patients aged >70. In most analyses, the impact of medical comorbidity (MC) has not been assessed. Efficacy and safety of adjuvant XELOX/FOLFOX versus LV/5-FU were compared with respect to age and MC using pooled data from four randomized, controlled trials, selected for access to patient-level MC data and including commonly endorsed and utilized regimens. PATIENTS AND METHODS: Individual data from patients with stage III CC in NSABP C-08, XELOXA, X-ACT, and AVANT were pooled, excluding bevacizumab-treated patients. Patients were grouped by treatment, MC (low versus high), or age (<70 versus ≥70), and compared for disease-free survival (DFS), overall survival (OS), and adverse events (AEs). Multivariable Cox proportional hazards regression controlled for gender, T stage, and N stage. RESULTS: DFS benefits were shown for XELOX/FOLFOX versus LV/5-FU regardless of age or MC, although benefits were modestly attenuated for patients aged ≥70. Hazard ratios were 0.68 (P < 0.0001) and 0.77 (P < 0.014) for <70 and ≥70 age groups; 0.69 (P < 0.0001) and 0.59 (P < 0.0001) for Charlson Comorbidity Index ≤1 and >1 groups; and 0.70 (P < 0.0001) and 0.58 (P < 0.0001) for National Cancer Institute Combined Index ≤1 and >1 groups. OS was also significantly improved in all groups. Grade 3/4 serious AE rates were comparable across cohorts and MC scores and higher in patients aged ≥70. Oxaliplatin-relevant grade 3/4 AEs, including neuropathy, were comparable across ages and MC scores. CONCLUSIONS: Results further support consideration of XELOX or FOLFOX as standard treatment options for the adjuvant management of stage III CC in all age groups and in patients with comorbidities, consistent with those who were eligible for these clinical trials.

Journeys of adjustment: the experiences of adolescents living with juvenile idiopathic arthritis.

BACKGROUND: Juvenile idiopathic arthritis (JIA) is one of the most common diseases of childhood causing pain, swelling of joints and reduced mobility. Previous research has focused on the challenges and psychosocial impact of JIA, but there has been limited attention given to how young people adjust and adapt to living with a long-term condition such as JIA. The aim of this qualitative study was therefore to explore adolescents' experiences of living with JIA, with particular focus on the process of adjustment. METHODS: Ten adolescents (7 female, 3 male) aged 13-17 years with good treatment adherence were recruited from an adolescent arthritis clinic. In-depth interviews were conducted, and data were analysed by two researchers independently using interpretative phenomenological analysis. RESULTS: These adolescents described the physical and psychosocial 'burden of living with JIA' and the challenges faced by an underlying preoccupation 'to be a normal teenager'. However, their accounts also revealed ways in which they regained agency and developed 'resilience through taking control' over their lives. This resilience helped the adolescents re-establish a sense of well-being through an ongoing process of 'acceptance and self-growth'. CONCLUSIONS: Although much research has adopted a deficit model that focuses on adjustment problems, the current study highlights the resourcefulness of young people in managing the challenges of living with a long-term condition. These experiences of successful adjustment can be used as the basis of positive, strength-based intervention approaches for adolescents with arthritis to enhance resilience and well-being.

Epidemiology and natural history of central venous access device use and infusion pump function in the NO16966 trial.

BACKGROUND: Central venous access devices in fluoropyrimidine therapy are associated with complications; however, reliable data are lacking regarding their natural history, associated complications and infusion pump performance in patients with metastatic colorectal cancer. METHODS: We assessed device placement, use during treatment, associated clinical outcomes and infusion pump performance in the NO16966 trial. RESULTS: Device replacement was more common with FOLFOX-4 (5-fluorouracil (5-FU)+oxaliplatin) than XELOX (capecitabine+oxaliplatin) (14.1% vs 5.1%). Baseline device-associated events and post-baseline removal-/placement-related events occurred more frequently with FOLFOX-4 than XELOX (11.5% vs 2.4% and 8.5% vs 2.1%). Pump malfunctions, primarily infusion accelerations in 16% of patients, occurred within 1.6-4.3% of cycles. Fluoropyrimidine-associated grade 3/4 toxicity was increased in FOLFOX-4-treated patients experiencing a malfunction compared with those who did not (97 out of 155 vs 452 out of 825 patients), predominantly with increased grade 3/4 neutropenia (53.5% vs 39.8%). Febrile neutropenia rates were comparable between patient cohorts±malfunction. Efficacy outcomes were similar in patient cohorts±malfunction. CONCLUSIONS: Central venous access device removal or replacement was common and more frequent in patients receiving FOLFOX-4. Pump malfunctions were also common and were associated with increased rates of grade 3/4 haematological adverse events. Oral fluoropyrimidine-based regimens may be preferable to infusional 5-FU based on these findings.

Effect of the 12-gene colon cancer assay results on adjuvant treatment recommendations in patients with stage II colon cancer.

INTRODUCTION: The 12-gene colon cancer Recurrence Score assay is a clinically validated predictor of recurrence risk in stage II colon cancer patients. A survey was performed characterizing the assay's impact on treatment recommendations for these patients. METHODS: US medical oncologists (n = 346) who ordered the assay for ≥3 stage II colon cancer patients were asked to complete a web-based survey regarding their most recent such patient. Physicians surveyed represented users of the assay within the first 2 years of commercial availability which may include 'early adopters'. RESULTS: Most of 116 eligible physicians were in community practice (86%), with median 14.5 years' experience (range = 2-40). Mean patient age was 61 years (range = 32-85); 81% had T3 disease, and 38% had comorbidities. Of 76 patients tested for mismatch-repair/microsatellite-instability (MMR/MSI), 13 (17%) were MMR-deficient/MSI-high; 46 (61%) MMR-proficient/MSI-low; and 17 (22%) unknown. Most patients (84%) had ≥12 nodes examined. Median Recurrence Score result was 20 (range = 1-77). Before assay, treatment recommendations were specified for 92 (79%) patients, with no recommendation for 24 (21%). Of the 92 with pre-assay recommendations, chemotherapy was planned for 52 (57%) and observation for 40 (43%); the assay changed recommendations for 27 (29%). Treatment intensity decreased for 18 (67%) and increased for nine (33%) patients; it was more likely to decrease for lower Recurrence Score values and increase for higher values (p < 0.001). CONCLUSION: For stage II colon cancer patients receiving Recurrence Score testing, 29% of treatment recommendations were changed. Use of the assay may lead to reductions in treatment intensity. Study limitations include retrospective design, data gathering during the first 2 years of assay availability only, and potential non-representativeness of respondents.

Phase II study of eribulin mesylate (E7389) in patients with metastatic castration-resistant prostate cancer stratified by prior taxane therapy.

BACKGROUND: Treatment options remain limited for patients with castration-resistant prostate cancer (CRPC). We evaluated eribulin mesylate (E7389), a nontaxane halichondrin B analog microtubule inhibitor, in patients with metastatic CRPC with or without previous taxane exposure. PATIENTS AND METHODS: Men with histologically proven CRPC, with or without prior taxane exposure, were enrolled in an open-label, single-arm phase II trial. Patients received eribulin mesylate 1.4 mg/m(2) as a 2- to 5-min i.v. bolus infusion on days 1 and 8 of a 21-day cycle. The primary efficacy end point was prostate-specific antigen (PSA) response rate. RESULTS: In total, 108 patients were assessable for safety (50 were taxane-pretreated) and 105 for efficacy in the per-protocol population. The median age of patients was 71 years and median number of cycles was 4. PSA decreases of ≥ 50% were achieved in 22.4% and 8.5% of taxane-naive and taxane-pretreated patients, respectively. The most common grade 3/4 adverse event was neutropenia, seen in 22.4% of chemo-naive and 40% of taxane-pretreated men. Grade 3 peripheral neuropathy occurred in none of the taxane-naive patients and 6.0% of taxane-pretreated patients. CONCLUSION: Eribulin mesylate demonstrated activity and a relatively favorable toxicity profile in metastatic CRPC.

Illness perceptions, coping and quality of life in patients with alopecia.

BACKGROUND: Alopecia can have substantial psychological consequences, but there has been no research looking at patients' beliefs about their condition nor how they relate to quality of life (QoL). OBJECTIVES: To investigate the relationships between illness perceptions, coping and QoL in patients with alopecia. METHODS: The study employed a cross-sectional design. In total, 214 individuals with alopecia were recruited from four internet support groups. There were 171 women and 43 men (mean age 35 years). Participants completed an online questionnaire comprising the Revised Illness Perception Questionnaire, the Dermatology Life Quality Index and the brief COPE. RESULTS: The findings indicate several areas in which alopecia impacted on individuals' QoL, particularly in relation to symptoms and feelings. Women reported poorer QoL compared with men. Impaired QoL was associated with a strong illness identity, beliefs in the serious consequences of alopecia and strong emotional representations. Hierarchical multiple regressions indicated that illness perceptions accounted for 35% of the variance in QoL after controlling for demographic and disease factors, with coping adding a further 7% to the regression model. CONCLUSIONS: Although alopecia is not a life-threatening condition, it can impair QoL by negatively impacting on self-awareness. The strong relationships found between patients' beliefs about their condition and QoL suggests that health professionals should recognize the psychological impact of alopecia and address negative beliefs and emotions surrounding the condition in treatment programmes.

Comparison of external and internal pelvic measurements of Belgian Blue cattle from sample herds in Belgium and the United kingdom.

Measurements describing pelvic conformation of pedigree Belgian Blue cows were obtained from a sample of nine herds in Flanders, Belgium, comprising 111 adult breeding cows, and from 11 herds in the United Kingdom comprising 108 similar cows. All herds in the Belgian sample (111 cows) managed parturition by elective caesarian section as did seven herds (56 cows) in the UK sample; the remainder of UK herds (52 cows) allowed cows the opportunity to calve naturally per vagina before resorting to caesarian section. The data described the external and internal measurements, and pelvic area characteristic of this breed, irrespective of the different selection pressures applied over a number of years to this breed through variation in farm management and market forces present in either country. From these data, generalized linear models were constructed to predict pelvic area; they correctly identified cows with either small or large pelvic areas. There were no significant differences in pelvic conformation between cattle bred either in Belgium or the UK, although those cows bred in herds where natural calving was allowed to take place had significantly larger internal pelvic height (p < 0.05) and area (p < 0.05) than other Belgian Blue cows. The correlation coefficients between internal pelvic height and width and external pelvic measurements were significant (p < 0.001). These results might facilitate the selection of breeding cows with larger pelvic area so that a higher proportion of cows can calve naturally than currently occurs. However, selection for other traits such as relatively low birth weight combined with higher weaning weight should be carried out at the same time.

An investigation of stress and pain perception during manual therapy in asymptomatic subjects.

Stress perceived by the patient during the application of a manual therapy treatment technique may account for the reported findings of sympathoexcitation and hypoalgesia immediately after its application. This study investigated whether there was a difference in the level of perceived stress and pain before, during and after the application of a treatment condition (treatment, placebo or control technique), or whether the difference related to the time course of subject involvement in the study.Twenty-four asymptomatic subjects participated in a double-blind, placebo-controlled, within-subjects study in which stress was measured with a stress rating scale and a stress visual analogue scale. Pain experienced by the subject during the application of the treatment technique was measured with a visual analogue scale and modified McGill pain questionnaire. There was no effect of the treatment condition on perceived stress, but there was a reduction in stress levels over the time course of involvement in the experiment, as demonstrated by pre-application levels of stress. Pain was not produced by the treatment technique.This study demonstrated that stress and pain were not features of the lateral glide manipulation of the cervical spine in asymptomatic subjects. If the dorsal periaqueductal grey region is responsible for the initial effects of manual therapy, as has been previously suggested, then stress and pain do not appear to play a role in activating this system during the application of a manual therapy treatment technique in asymptomatic subjects. Copyright 1999 European Federation of Chapters of the International Association for the Study of Pain.

Interaction of human angiogenin with copper modulates angiogenin binding to endothelial cells.

Angiogenin is a potent inducer of blood-vessel formation with ribonucleolytic activity. Angiogenin binds to high affinity endothelial cell receptors and with lower affinity to extracellular matrix components. Here we report the effect of copper and zinc on these interactions. There was a 4.3-fold increase in angiogenin binding to calf pulmonary artery endothelial cells in the presence of Cu2+ in vitro. A 3.8-fold increase was observed with Zn2+, whereas Ni2+, Co2+, or Li+ had no effect. Specific angiogenin binding to the lower affinity matrix sites was increased by 2.7- and 1.9-fold in the presence of Cu2+ and Zn2+ respectively. Metal ion affinity chromatography and atomic absorption spectrometry were used to show the direct interaction of angiogenin with copper and zinc ions. Angiogenin bound 2.4 mol of copper per mole of protein. We suggest that copper, a modulator of angiogenesis in vivo, may be involved in the regulation of the biological activity of angiogenin.

Syntactic categorization in early language acquisition: formalizing the role of distributional analysis.

We propose an explicit, incremental strategy by which children could group words with similar syntactic privileges into discrete, unlabeled categories. This strategy, which can discover lexical ambiguity, is based in part on a generalization of the idea of sentential minimal pairs. As a result, it makes minimal assumptions about the availability of syntactic knowledge at the onset of categorization. Although the proposed strategy is distributional, it can make use of categorization cues from other domains, including semantics and phonology. Computer simulations show that this strategy is effective at categorizing words in both artificial-language samples and transcripts of naturally-occurring, child-directed speech. Further, the simulations show that the proposed strategy performs even better when supplied with semantic information about concrete nouns. Implications for theories of categorization are discussed.

Distributional regularity and phonotactic constraints are useful for segmentation.

In order to acquire a lexicon, young children must segment speech into words, even though most words are unfamiliar to them. This is a non-trivial task because speech lacks any acoustic analog of the blank spaces between printed words. Two sources of information that might be useful for this task are distributional regularity and phonotactic constraints. Informally, distributional regularity refers to the intuition that sound sequences that occur frequently and in a variety of contexts are better candidates for the lexicon than those that occur rarely or in few contexts. We express that intuition formally by a class of functions called DR functions. We then put forth three hypotheses: First, that children segment using DR functions. Second, that they exploit phonotactic constraints on the possible pronunciations of words in their language. Specifically, they exploit both the requirement that every word must have a vowel and the constraints that languages impose on word-initial and word-final consonant clusters. Third, that children learn which word-boundary clusters are permitted in their language by assuming that all permissible word-boundary clusters will eventually occur at utterance boundaries. Using computational simulation, we investigate the effectiveness of these strategies for segmenting broad phonetic transcripts of child-directed English. The results show that DR functions and phonotactic constraints can be used to significantly improve segmentation. Further, the contributions of DR functions and phonotactic constraints are largely independent, so using both yields better segmentation than using either one alone. Finally, learning the permissible word-boundary clusters from utterance boundaries does not degrade segmentation performance.

Natural and structured baselines in the treatment of aggression following brain injury.

This single-case study describes the importance of presenting relevant baseline conditions in planning and evaluating treatment for aggression in a severely brain injured man 1 year after injury. An artificially low natural baseline resulted from staff reluctance to deliver instructions and corrective feedback needed for rehabilitation of self-care skill because these were frequently followed by aggression. A subsequent structured baseline presented these antecedents at the higher rates that were necessary for progress in the patient's rehabilitation. This resulted in an increase in aggressive behaviour, but also gave a more accurate representation of what his behaviour would be like under effective rehabilitation conditions. Intervention was based on data from the structured baseline, and included providing clear expectations, social reinforcement, and decelerative procedures. After reduction of aggression to zero, regular staff were reintroduced and presented instruction and corrective feedback as required. No further aggressive behaviour was noted, and self-care improved so that only minimal assistance was needed. Six months following reintroduction of regular staff, both baseline conditions were replicated. No aggressive behaviour was observed during either, suggesting that maintenance of gains could not be attributed to an artificially reduced rate caused by staff avoiding trigger antecedents.

Immediate Diagnosis of Ankle Trauma.

In brief Traumatic Injuries to the ankle vary greatly in severity, from minor contusions to displaced intra-articular fractures. A systematic approach to their evaluation can lead to more accurate diagnoses and help simplify treatment options. Primary care physicians can successfully manage most sports-related ankle trauma, but knowing when to obtain orthopedic consultation is equally important.

How to clear fogged lenses within the arthroscopic camera bag.

Arthroscopic camera bags are extremely practical because they allow multiple procedures to be performed in the same day. This is especially true for small community hospitals where equipment is limited. Unfortunately, the plastic creates a greenhouse effect, allowing any moisture that is present to condense and fog the camera and scope. By using sponges placed inside the camera bag to wipe the optical lenses, the surgeon can improve visualization during an arthroscopic procedure if fogging becomes a problem.

Traumatic rupture of an aortic ulcerative atherosclerotic plaque producing aortic dissection: a complication of interscapular back blows used to dislodge objects from the esophagus.

Penetrating atherosclerotic ulcer of the aorta is a rare entity which usually occurs in the descending thoracic aorta. Herein, we report an unusual case of penetrating aortic ulcer which ruptured into the mediastinum. Interscapular back blows were performed on our patient in an attempt to dislodge an aspirin which she thought was lodged in her esophagus. Unlike previously reported cases of this entity, the penetrating aortic ulcer in our patient was located in the distal thoracic ascending aorta. Diagnosis of penetrating aortic ulcer can be made by utilizing aortography, contiguous dynamic contrast-enhanced computed tomography or magnetic resonance imaging. Treatment consists of adjunctive medical therapy until surgery can be performed.

Process economics of animal cell and bacterial fermentations: a case study analysis of tissue plasminogen activator.

One link in the complex chain of medical economics is the cost of bringing new drugs and biologicals to the market. Advances in recombinant-DNA technology permit production of therapeutically active proteins in effectively unlimited quantities. Nevertheless, each expression system has a characteristic influence on the nature of the product produced and the process required to obtain it. In this case study we compare experiences with recombinant-tissue plasminogen activator (rtPA) produced in Chinese hamster ovary (CHO) cells and in Escherichia coli, with the aim of understanding the roles of some of the parameters that affect process economics. tPA belongs to the group of highly specific serine proteases that convert plasminogen to plasmin, which in turn degrades several protein substrates including fibrin, thus making it an effective thrombolytic agent. The treatment of acute myocardial infarction with such thrombolytic agents can result in early discharge of patients and decreased medical costs. However, there are major differences in the prices of the various available agents. The price of the FDA-licensed tPA product is $2,200 per dose or $22,000 per gram. It is believed that a significant portion of this price relates to manufacturing costs. We examine by way of case study illustration the cost breakdown for the two processes, and highlight important process, design and economic considerations that ultimately define a particular protein product.

Performance of three tropical hair sheep breeds.

The performance of three hair sheep breeds (Brazilian Somali, Morada Nova, and Santa Ines) was evaluated in the production environment of northeastern Brazil. Data from a total of 524 lambs sired by 21 rams and out of 190 ewes were analyzed. These data were collected from 1980 to 1983 at Sobral, Brazil from an experiment designed to compare performance of the three breeds. The traits included weights of lambs at birth, weaning, 8 mo, 10 mo, and yearling ages and ewe characters of weight at lambing (EWT), total lamb weight born (LWB), total lamb weight weaned (LWW), and prolificacy rate (PR). Differences (P < .01) among breeds were found for all characters. The Brazilian Somali, the smallest and slowest-gaining breed, was less sensitive to yearly variation than were the other breeds. The Santa Ines, the largest and fastest-gaining breed, was superior in LWB and LWW per ewe lambing. Averaged over the 4-yr period, the Morada Nova had the highest PR (1.82), and the Brazilian Somali and Santa Ines had similar PR (1.39 and 1.31, respectively). Environmental effects on PR due to yearly rainfall quantity and distribution pattern influenced lamb growth up to weaning and ewe reproduction performance. Breed x year (P < .05) interaction effects on PR were largely attributable to the Somali breed's exhibiting higher PR than the Santa Ines and Morada Nova breeds during the relatively wet years of 1981 and 1982.

Moral philosophy and nursing curricula: indoctrination of the new breed.

A sizable proportion of nursing curricula subtly indoctrinate students with a particular normative ethic. Seldom is there adequate philosophical justification for the ethic, and students are rarely invited to subject that ethic to a rigorous philosophical analysis. Nursing curricula are replete with philosophical positions treated as moral imperatives to which all, students and faculty, owe their allegiance. This unsatisfactory situation warrants urgent attention. One problem is that of failing to justify the school's moral philosophy; another is the question of philosophically indoctrinating students to adhere to an ethic that advocates the individual's freedom and responsibility, a practice inconsistent with the predominant proposition advanced by the ethic.