Analyses of systems theory for construction accident prevention with specific reference to OSHA accident reports

To enhance workplace safety in the construction industry it is important to understand interrelationships among safety risk factors associated with construction accidents. This study incorporates the systems theory into Heinrich’s domino theory to explore the interrelationships of risks and break the chain of accident causation. Through both empirical and statistical analyses of 9,358 accidents which occurred in the U.S. construction industry between 2002 and 2011, the study investigates relationships between accidents and injury elements (e.g., injury type, part of body, injury severity) and the nature of construction injuries by accident type. The study then discusses relationships between accidents and risks, including worker behavior, injury source, and environmental condition, and identifies key risk factors and risk combinations causing accidents. The research outcomes will assist safety managers to prioritize risks according to the likelihood of accident occurrence and injury characteristics, and pay more attention to balancing significant risk relationships to prevent accidents and achieve safer working environments.

Gene expression profile of primary prostate epithelial and stromal cells in response to sulforaphane or iberin exposure

BACKGROUND: Broccoli consumption has been associated with a reduced risk of prostate cancer. Isothiocyanates (ITCs) derived from glucosinolates that accumulate in broccoli are dietary compounds that may mediate these health effects. Sulforaphane (SF, 4-methylsulphinylbutyl ITC) derives from heading broccoli (calabrese) and iberin (IB, 3-methylsulphinypropyl ITC) from sprouting broccoli. While there are many studies regarding the biological activity of SF, mainly undertaken with cancerous cells, there are few studies associated with IB. METHODS: Primary epithelial and stromal cells were derived from benign prostatic hyperplasia tissue. Affymetrix U133 Plus 2.0 whole genome arrays were used to compare global gene expression between these cells, and to quantify changes in gene expression following exposure to physiologically appropriate concentrations of SF and IB. Ontology and pathway analyses were used to interpret results. Changes in expression of a subset of genes were confirmed by real-time RT-PCR. RESULTS: Global gene expression profiling identified epithelial and stromal-specific gene expression profiles. SF induced more changes in epithelial cells, whereas IB was more effective in stromal cells. Although IB and SF induced different changes in gene expression in both epithelial and stromal cells, these were associated with similar pathways, such as cell cycle and detoxification. Both ITCs increased expression of PLAGL1, a tumor suppressor gene, in stromal cells and suppressed expression of the putative tumor promoting genes IFITM1, CSPG2, and VIM in epithelial cells. CONCLUSION: These data suggest that IB and SF both alter genes associated with cancer prevention, and IB should be investigated further as a potential chemopreventative agent.

BRCA1 is an essential mediator of vinorelbine-induced apoptosis in mesothelioma

The rapeutic options for malignant pleural mesothelioma (MPM) are limited despite the increasing incidence globally. The vinca alkaloid vinorelbine exhibits clinical activity; however, to date, treatment optimization has not been achieved using biomarkers. BRCA1 regulates sensitivity to microtubule poisons; however, its role in regulating vinorelbine-induced apoptosis in mesothelioma is unknown. Here we demonstrate that BRCA1 plays an essential role in mediating vinorelbine-induced apoptosis, as evidenced by (1) the strong correlation between vinorelbine sensitivity and BRCA1 expression level; (2) induction of resistance to vinorelbine by BRCA1 using siRNA oligonucleotides; (3) dramatic down-regulation of BRCA1 following selection for vinorelbine resistance; and (4) the re-activation of vinorelbine-induced apoptosis following re-expression of BRCA1 in resistant cells. To determine whether loss of BRCA1 expression in mesothelioma was potentially relevant in vivo, BRCA1 immunohistochemistry was subsequently performed on 144 primary mesothelioma specimens. Loss of BRCA1 protein expression was identified in 38.9% of samples. Together, these data suggest that BRCA1 plays a critical role in mediating apoptosis by vinorelbine in mesothelioma, warranting its clinical evaluation as a predictive biomarker. Copyright © 2012 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.

Differentiating first episode substance induced and primary psychotic disorders with concurrent substance use in young people

Objective: Substance use is common in first-episode psychosis, and complicates the accurate diagnosis and treatment of the disorder. The differentiation of substance-induced psychotic disorders (SIPD) from primary psychotic disorders (PPD) is particularly challenging. This cross-sectional study compares the clinical, substance use and functional characteristics of substance using first episode psychosis patients diagnosed with a SIPD and PPD. Method: Participants were 61 young people (15-24 years) admitted to a psychiatric inpatient service with first episode psychosis, reporting substance use in the past month. Diagnosis was determined using the Psychiatric Research Interview for DSM-IV Substance and Mental disorders (PRISM-IV). Measures of clinical (severity of psychotic symptoms, level of insight, history of trauma), substance use (frequency/quantity, severity) and social and occupational functioning were also administered. Results: The PRISM-IV differentially diagnosed 56% of first episode patients with a SIPD and 44% with a PPD. Those with a SIPD had higher rates of substance use and disorders, higher levels of insight, were more likely to have a forensic and trauma history and had more severe hostility and anxious symptoms than those with a PPD. Logistic regression analysis indicated a family history of psychosis, trauma history and current cannabis dependence were the strongest predictors of a SIPD. Almost 80% of diagnostic predictions of a SIPD were accurate using this model. Conclusions: This clinical profile of SIPD could help to facilitate the accurate diagnosis and treatment of SIPD versus PPD in young people with first episode psychosis admitted to an inpatient psychiatric service.

Effect of mobile phone-based psychotherapy in suicide prevention : a randomized controlled trial in Sri Lanka

We conducted a randomized controlled trial to test whether a Brief Mobile Treatment (BMT) intervention could improve outcomes relative to usual care among suicide attempters. The intervention included training in problem solving therapy, meditation, a brief intervention to increase social support as well as advice on alcohol and other drugs, and mobile phone follow-up. The effect of the intervention was measured in terms of a reduction in suicidal ideation, depression and self-harm at Baseline, six and 12 months. A wait-list control group received usual care. A total of 68 participants was recruited from a Sri Lankan hospital following a suicide attempt. Participants who received the intervention were found to achieve significant improvements in reducing suicidal ideation and depression than those receiving usual care. The BMT group also experienced a significant improvement of social support when compared to the control group. However, the BMT group did not demonstrate a significant effect in reducing actual self-harm and most substance use, and differential effects on alcohol use were restricted to men. Although the present study was limited in revealing which component of the intervention was more effective in preventing suicide, it showed its efficacy in reducing suicide as a whole.

Upper-body morbidity after breast cancer : incidence and evidence for evaluation, prevention, and management within a prospective surveillance model of care

The purpose of this paper is to review the incidence of upper-body morbidity (arm and breast symptoms, impairments, and lymphedema), methods for diagnosis, and prevention and treatment strategies. It was also the purpose to highlight the evidence base for integration of prospective surveillance for upper-body morbidity within standard clinical care of women with breast cancer. Between 10% and 64% of women report upper-body symptoms between 6 months and 3 years after breast cancer, and approximately 20% develop lymphedema. Symptoms remain common into longer-term survivorship, and although lymphedema may be transient for some, those who present with mild lymphedema are at increased risk of developing moderate to severe lymphedema. The etiology of morbidity seems to be multifactorial, with the most consistent risk factors being those associated with extent of treatment. However, known risk factors cannot reliably distinguish between those who will and will not develop upper-body morbidity. Upper-body morbidity may be treatable with physical therapy. There is also evidence in support of integrating regular surveillance for upper-body morbidity into the routine care provided to women with breast cancer, with early diagnosis potentially contributing to more effective management and prevention of progression of these conditions.

Genetic polymorphisms in the human tissue kallikrein (KLK) locus and their implication in various malignant and non-malignant diseases

The Kallikrein (KLK) gene locus encodes a family of serine proteases and is the largest contiguous cluster of protease-encoding genes attributed an evolutionary age of 330 million years. The KLK locus has been implicated as a high susceptibility risk loci in numerous cancer studies through the last decade. The KLK3 gene already has established clinical relevance as a biomarker in prostate cancer prognosis through its encoded protein, prostate-specific antigen. Data mined through genome-wide association studies (GWAS) and next-generation sequencing point to many important candidate single nucleotide polymorphisms (SNPs) in KLK3 and other KLK genes. SNPs in the KLK locus have been found to be associated with several diseases including cancer, hypertension, cardiovascular disease and atopic dermatitis. Moreover, introducing a model incorporating SNPs to improve the efficiency of prostate-specific antigen in detecting malignant states of prostate cancer has been recently suggested. Establishing the functional relevance of these newly-discovered SNPs, and their interactions with each other, through in silico investigations followed by experimental validation, can accelerate the discovery of diagnostic and prognostic biomarkers. In this review, we discuss the various genetic association studies on the KLK loci identified either through candidate gene association studies or at the GWAS and post-GWAS front to aid researchers in streamlining their search for the most significant, relevant and therapeutically promising candidate KLK gene and/or SNP for future investigations.

Changing learning to improve practice : hand hygiene education in Queensland medical schools

The aim of Queensland Health’s ‘Clean hands are life savers’ program is to change the culture and behaviour of healthcare workers related to hand hygiene. Hand hygiene is considered to be the most effective means of preventing pathogen cross-transmission and healthcare-associated infections. Most hospitals throughout Queensland as well as Australia now manage a hand hygiene program to increase the hand hygiene compliance of all healthcare workers. Reports taken from routine hand hygiene observations reveal that doctors are usually less compliant in their hand-washing practices than other healthcare worker groups. The Centre for Healthcare Related Infection Surveillance and Prevention (CHRISP) has attempted to have an impact on this challenging group through their Medical Leadership Initiative. With education as a core component of the program, efforts were made to ensure our future doctors were receiving information that aligned with Queensland Health standards during their formative years at medical school. CHRISP met with university instructors to understand what infection prevention education was currently included in the curriculum and support the introduction of new learning activities that specifically focused on hand hygiene. This prompted change to the existing curriculum and a range of interventions were employed with mixed success. Although met with challenges, methods to integrate more infection prevention teaching were found.

Calcite precipitation induced by clay-bleach cation exchange in andesitic reservoir rocks

Experiments were carried out on the sodium hypochlorite bleach sensitivity of a deep subsurface andesitic reservoir in order to predict possible deleterious mineral transformations during a downhole clean-up job. Experiments involved examination of core samples from the reservoir using an Environmental Scanning Electron Microscope (ESEM) with an attached Energy Dispersive Spectrometer (EDS) before and after the samples were immersed in bleach. Bleach immersion of whole-rock samples resulted in rapid (less than 1 min) precipitation of abundant 3.0-10.0-μm-wide calcite rhombs within clay-associated micropores and on clay and feldspar grain surfaces. Abundant microporefilling calcite rhombs also formed in pure separates of constituent chlorite/corrensite, whereas no calcite formed in a pure separate of constituent zeolite. These experiments indicate that corrensite is the likely calcium source in this experimental fluid-rock system. Formation of calcite occurs via a cation exchange reaction in which calcium in the smectitic interlayers of corrensite exchanges for sodium in the bleach. Serious formation damage due to calcite precipitation would have occurred in the andesite reservoir had it been exposed to bleach. This finding gives credence to earlier suggestions that cation exchange reactions have the potential to cause calcite precipitation in some sandstone reservoirs when exposed to drilling, completion or stimulation fluids. © 1993.

Paclitaxel resistance and multicellular spheroid formation are induced by kallikrein-related peptidase 4 in serous ovarian cancer cells in an ascites mimicking microenvironment

High tumor kallikrein-related-peptidase 4 (KLK4) levels are associated with a poor outcome for women with serous epithelial ovarian cancer (EOC), for which peritoneal dissemination and chemoresistance are key events. To determine the role of KLK4 in these events, we examined KLK4-transfected SKOV-3 and endogenous KLK4 expressing OVCA432 cells in 3-dimensional (3D) suspension culture to mimic the ascites microenvironment. KLK4-SKOV-3 cells formed multicellular aggregates (MCAs) as seen in ascites, as did SKOV-3 cells treated with active KLK4. MCA formation was reduced by treatment with a KLK4 blocking antibody or the selective active site KLK4 sunflower trypsin inhibitor (SFTI-FCQR). KLK4-MCAs formed larger cancer cell foci in mesothelial cell monolayers than those formed by vector and native SKOV-3 cells, suggesting KLK4-MCAs are highly invasive in the peritoneal microenvironment. A high level of KLK4 is expressed by ascitic EOC cells compared to matched primary tumor cells, further supporting its role in the ascitic microenvironment. Interestingly, KLK4 transfected SKOV-3 cells expressed high levels of the KLK4 substrate, urokinase plasminogen activator (uPA), particularly in 3D-suspension, and high levels of both KLK4 and uPA were observed in patient cells taken from ascites. Importantly, the KLK4-MCAs were paclitaxel resistant which was reversed by SFTI-FCQR and to a lesser degree by the general serine protease inhibitor, Aprotinin, suggesting that in addition to uPA, other as yet unidentified substrates of KLK4 must be involved. Nonetheless, these data suggest that KLK4 inhibition, in conjunction with paclitaxel, may improve the outcome for women with serous epithelial ovarian cancer and high KLK4 levels in their tumors.