Data driven optimization of sexual assault case processing.

In recent years, several forensic laboratories have noted an increase in the number of sexual assault cases submitted for testing, often leading to longer turnaround times. In that context, forensic laboratories may be interested in reviewing their procedures to increase productivity. Here, we present two different strategies that were put in place in our laboratory. First, we changed the way sexual assault evidence kits (SAEK) are processed by implementing an optimized workflow that prioritizes the internal samples (vaginal, anal, and oral). This new procedure allowed for a drastic decrease in turnaround time, while maintaining a similar investigative power. Secondly, we used data from casework to target cases and samples that were likely to yield biological material from the perpetrator, in an attempt to avoid dedicating time and effort to cases for which there is a very low probability of obtaining foreign DNA evidence. Among other things, we looked at the likelihood of obtaining DNA from the perpetrator when the complainant reported the use of a condom, has showered after the assault or when the complainant has no memory of the assault. Results show that those circumstances do not dramatically decrease the probability of finding DNA from the perpetrator.

CSACI guidelines for the ethical, evidence-based and patient-oriented clinical practice of oral immunotherapy in IgE-mediated food allergy.

BACKGROUND: Oral immunotherapy (OIT) is an emerging approach to the treatment of patients with IgE-mediated food allergy and is in the process of transitioning to clinical practice. OBJECTIVE: To develop patient-oriented clinical practice guidelines on oral immunotherapy based on evidence and ethical imperatives for the provision of safe and efficient food allergy management. MATERIALS AND METHODS: Recommendations were developed using a reflective patient-centered multicriteria approach including 22 criteria organized in five dimensions (clinical, populational, economic, organizational and sociopolitical). Data was obtained from: (1) a review of scientific and ethic literature; (2) consultations of allergists, other healthcare professionals (pediatricians, family physicians, nurses, registered dieticians, psychologists, peer supporters), patients and caregivers; and patient associations through structured consultative panels, interviews and on-line questionnaire; and (3) organizational and economic data from the milieu of care. All data was synthesized by criteria in a multicriteria deliberative guide that served as a platform for structured discussion and development of recommendations for each dimension, based on evidence, ethical imperatives and other considerations. RESULTS: The deliberative grid included 162 articles from the literature and media reviews and data from consultations involving 85 individuals. Thirty-eight (38) recommendations were made for the practice of oral immunotherapy for the treatment of IgE mediated food allergy, based on evidence and a diversity of ethical imperatives. All recommendations were aimed at fostering a context conducive to achieving objectives identified by patients and caregivers with food allergy. Notably, specific recommendations were developed to promote a culture of shared responsibility between patients and healthcare system, equity in access, patient empowerment, shared decision making and personalization of OIT protocols to reflect patients' needs. It also provides recommendations to optimize organization of care to generate capacity to meet demand according to patient choice, e.g. OIT or avoidance. These recommendations were made acknowledging the necessity of ensuring sustainability of the clinical offer in light of various economic considerations. CONCLUSIONS: This innovative CPG methodology was guided by patients' perspectives, clinical evidence as well as ethical and other rationales. This allowed for the creation of a broad set of recommendations that chart optimal clinical practice and define the conditions required to bring about changes to food allergy care that will be sustainable, equitable and conducive to the well-being of all patients in need.

Internationally educated nurses in Canada: perceived benefits of bridging programme participation.

AIM: To examine internationally educated nurses' perceptions of the extent to which participating in bridging programmes is beneficial for preparing to practise nursing in Canada. BACKGROUND: Internationally educated nurses continue to migrate from low-income to high-income countries. Many experience challenges when attempting to practise their profession in the destination country. Canada and other top destination countries offer educational support, such as bridging programmes, to assist internationally educated nurses' with preparing to practise nursing in the destination country. The research evidence falls short in demonstrating the usefulness of bridging programmes. METHODS: A subsample of 360 internationally educated nurse participants from a Canadian cross-sectional survey conducted in 2014. All were permanent residents, employed as regulated nurses and participants of bridging programmes. Multiple linear regression was employed to examine the influence of internationally educated nurses' human capital (academic preparation, language proficiency, professional experience) and the economic status of their source country on perceived benefits of bridging programme participation. RESULTS: Regression model explained 11.5% of variance in perceived benefits of bridging programme participation. Two predictors were statistically significant: source country and professional experience. CONCLUSION: Bridging programmes help internationally educated nurses address gaps in their cultural, practical and theoretical knowledge. Source country and amount of professionally experience influences the extent to which internationally educated nurses benefit from participating in bridging programmes in Canada. IMPLICATIONS FOR NURSING POLICY: Provides emerging evidence for decision-makers globally when developing policies and supports to help internationally educated nurses integrate into the destination country's nursing workforce.

CdGAP is required for transforming growth factor ß- and Neu/ErbB-2-induced breast cancer cell motility and invasion.

RhoA, Rac1 and Cdc42, the best-characterized members of the Rho family of small GTPases, are critical regulators of many cellular activities. Cdc42 GTPase-activating protein (CdGAP) is a serine- and proline-rich RhoGAP protein showing GAP activity against both Cdc42 and Rac1 but not RhoA. CdGAP is phosphorylated downstream of the MEK-ERK (extracellular signal-regulated kinase) pathway in response to serum and is required for normal cell spreading and polarized lamellipodia formation. In this study, we found that CdGAP protein and mRNA levels are highly increased in mammary tumor explants expressing an activated Neu/ErbB-2 (Neu-NT) receptor. In response to transforming growth factor-ß (TGFß) stimulation, Neu-NT-expressing mammary tumor explants demonstrate a clear induction in cell motility and invasion. We show that downregulation of CdGAP expression by small interfering RNA abrogates the ability of TGFß to induce cell motility and invasion of Neu-NT-expressing mammary tumor explants. However, it has no effect on TGFß-mediated cell adhesion on type 1 collagen and fibronectin. Interestingly, protein expression of E-Cadherin is highly increased in Neu-NT-expressing mammary tumor explants depleted of CdGAP. In addition, complete loss of E-Cadherin expression is not observed in CdGAP-depleted cells during TGFß-mediated epithelial to mesenchymal transition. Downregulation of the CdGAP expression also decreases cell proliferation of Neu-NT-expressing mammary tumor explants independently of TGFß. Rescue analysis using re-expression of various CdGAP deletion-mutant proteins revealed that the proline-rich domain (PRD) but not the GAP domain of CdGAP is essential to mediate TGFß-induced cell motility and invasion. Finally, we found that TGFß induces the expression and phosphorylation of CdGAP in mammary epithelial NMuMG cells. Taken together, these studies identify CdGAP as a novel molecular target in TGFß signaling and implicate CdGAP as an essential component in the synergistic interaction between TGFß and Neu/ErbB-2 signaling pathways in breast cancer cells.

Combining several polymorphisms of thymidylate synthase gene for pharmacogenetic analysis.

Thymidylate synthase (TS) is an essential enzyme in proliferating cells and an important target for several chemotherapeutics. Several TS gene polymorphisms correlate with variable TS expression: a double (2R) and triple (3R) 28-bp repeat element, a G to C substitution of the 3R allele and a 6 bp variation in 3'UTR. We have previously shown that childhood acute lymphoblastic leukemia (ALL) patients who are homozygous for the 3R allele had reduced event-free survival (EFS) probabilities. Here, we analyzed all three polymorphisms in an extended group of ALL patients (n=259). The effect of the 3R homozygosity on ALL outcome was confirmed (P=0.006), whereas 6 bp polymorphism did not influence EFS when analyzed separately. No significant difference among 3R3R genotype subgroups, as defined by a G to C substitution, was observed. The haplotype analysis revealed the higher frequency of the 3RC/6 bp+ haplotype (P=0.04) and the protective role of the 2R/6b p- (P=0.04). Consequently, homozygosity for the 6 bp- allele appeared to reduce an event-predisposing effect of 3R variant. Although of importance for translation into the clinical practice, these findings need confirmation in larger studies.

Role of polymorphisms in MTHFR and MTHFD1 genes in the outcome of childhood acute lymphoblastic leukemia.

The central role of 5,10-methylenetetrahydrofolate reductase (MTHFR) and methylenetetrahydrofolate dehydrogenase (MTHFD1) in folate metabolism renders polymorphisms in genes encoding these enzymes potential modulators of therapeutic response to antifolate chemotherapeutics. The analysis of 201 children treated with methotrexate for childhood acute lymphoblastic leukemia (ALL) showed that patients with either the MTHFR T677A1298 haplotype or MTHFD1 A1958 variant had a lower probability of event-free survival (EFS) in univariate analysis (hazard ratio (HR)=2.2, 95% confidence interval (CI), 1.0-4.7 and 2.8, 95% CI, 1.1-7.3, respectively). Multivariate analysis supported only the role of the MTHFR variant (HR=2.2, 95% CI, 0.9-5.6). However, the association of both genes with ALL outcome appears to be more obvious in the presence of another event-predisposing variant belonging to the same path of drug action. The combined effect of a thymidylate synthase (TS) triple repeat associated with increased TS levels, with either the MTHFR T677A1298 haplotype or MTHFD1 A1958 allele, resulted in a highly significant reduction of EFS (multivariate HR=9.0, 95% CI, 1.9-42.8 and 8.9, 95% CI, 1.8-44.6, respectively). These results reveal the role of gene-gene interactions within a folate pathway, and how they can correlate with relapse probabilities in ALL patients.

Repeated latex aeroallergen challenges employing a hooded exposure chamber: safety and reproducibility.

BACKGROUND: Bronchial, nasal, and conjunctival challenges are useful for clarifying discordant clinical history (Hx) and skin and/or serologic tests and in assessing semiquantitative changes in biologic sensitivity over time. The objective of this study was to determine the safety and reproducibility of repeated latex-allergen challenges with a hooded exposure chamber (HEC). METHODS: The HEC system comprises a powered forced-air respirator with a fitted face shield and hood that uses glove-derived latex-allergen associated cornstarch particles (LAC) to expose simultaneously the conjunctiva, nose, and lungs. Serial control and incremental LAC challenges are conducted until an endpoint based on upper and/or lower respiratory tract symptoms and peak expiratory flow rates is reached. Six latex-allergic (Hx and puncture skin test [PST]- and 5/6 radioallergosorbent test [RAST]-positive) subjects were challenged on three separate occasions at least 2 weeks apart. Serial latex PST midpoints and serum anti-latex IgE by RAST were monitored at each visit and at a fourth follow-up visit. RESULTS: All subjects responded to LAC, but not to air or control cornstarch administered as controls. All responses were confined to mild symptoms of allergic rhinoconjunctivitis and/or asthma that either resolved spontaneously or were reversed with inhaled albuterol. No subject experienced a systemic or delayed reaction. There were no significant changes in the endpoint LAC doses over the three challenge visits (P>0.2). The mean coefficient of variation for log2 endpoints within-subjects was 17.3+/-17.2% (SD). The serum latex-specific IgE was not significantly boosted by the three challenges (P>0.2). The concentration of latex extract necessary to produce an 8-mm wheal by PST was not significantly changed during the study (P>0.1), indicating that latex sensitivity was not affected by the repeated LAC exposures. CONCLUSIONS: The results of this study indicate that repeated HEC latex-allergen challenges are both reproducible and safe, and do not increase latex sensitivity.

Natural rubber pharmaceutical vial closures release latex allergens that produce skin reactions.

BACKGROUND: The release of allergenic proteins from natural rubber vial closures (stoppers) into aqueous pharmaceuticals may induce allergic reactions in individuals with latex allergy (LA) receiving medications from such vials. OBJECTIVE: The goal of this study was to determine whether solutions stored in vials containing natural rubber closures release allergenic proteins detectable by skin testing of subjects with LA. METHODS: Five pharmaceutical vial closures (2 natural rubber and 3 synthetic) were coded, inserted onto vials containing phenol-saline-human serum albumin, and stored in an inverted position before use. Twelve volunteers with and 11 volunteers without LA underwent skin testing with solutions from each of the 5 vials, either those not punctured (0P) or those punctured 40 times with a 21-gauge needle 12 to 24 hours before testing (40P). RESULTS: All intradermal skin test responses in the group without LA were negative. Two and 5 of the 12 subjects with LA had positive intradermal skin reactions to 0P and 40P solutions, respectively, from vials containing rubber closures. Two subjects with LA had inexplicable, positive, nonreproducible intradermal skin test reactions to solutions from vials containing bromobutyl but not vials with isoprene synthetic closures. In vitro inhibition analysis detected 6 to 7 AU/g latex allergen in extracts of cut natural rubber containing closures but not in extracts of synthetic closures. CONCLUSION: Natural rubber vial closures released allergenic latex proteins into the tested solutions in direct contact during storage in sufficient quantities to elicit positive intradermal skin reactions in some individuals with LA. These data support a recommendation to eliminate natural rubber from closures of pharmaceutical vials.

A battery-powered notebook thermal cycler for rapid multiplex real-time PCR analysis.

A compact, real-time PCR instrument was developed for rapid, multiplex analysis of nucleic acids in an inexpensive, portable format. The instrument consists of a notebook computer, two reaction modules with integrated optics for four-color fluorescence detection, batteries, and a battery-charging system. The instrument weighs 3.3 kg, measures 26 x 22 x 7.5 cm, and can run continuously on the internal batteries for 4 h. Independent control of the modules allows differing temperature profiles and detection schemes to be run simultaneously. Results are presented that demonstrate rapid (1) detection and identification of Bacillus subtilis and Bacillus thuringensis spores and (2) characterization of a single nucleotide polymorphism for the hereditary hemochromatosis gene.

Recent advances in the diagnosis of drug allergy.

The diagnosis of immunologic drug reactions is based primarily on a detailed clinical history and historical data on relative immunogenicity of the culprit drugs. Except for a few standardized skin tests, most of the other methods for diagnosing drug allergy have unproven diagnostic or predictive clinical utility. Many tests for drug-specific immune responses are suggestive if positive, but have unknown negative predictive values. The present review addresses the most recent published literature regarding the diagnosis of drug allergy. Recent advances in the use of the lymphocyte transformation test, and delayed intradermal skin tests and patch tests for the diagnosis of delayed cutaneous reactions to penicillins suggest that these tests may have clinical utility, although confirmatory reports are still missing. For the diagnosis of acute vaccine reactions, gelatin-specific IgE as measured by radioallergosorbent test has now been shown to be reliably associated with allergic reactions to gelatin-containing vaccines.

The psychological burden of peanut allergy as perceived by adults with peanut allergy and the parents of peanut-allergic children.

BACKGROUND: Peanut-allergic patients are affected by a condition which forces them and their families to exercise extreme dietary vigilance and experience constant uncertainty throughout their lives. OBJECTIVE: To compare the quality of life and family relations of children and adults with a peanut allergy to that of children and adults with a rheumatological disease. METHODS: Patients with a confirmed diagnosis of peanut allergy or a rheumatological disease completed (for children less than 18 years, by proxy) self-report questionnaires regarding the impact of their condition on their quality of life and family relations. A vertical visual analogue scale and the Impact on Family Questionnaire (IFQ) served as outcome measures. RESULTS: One hundred and fifty-three peanut-allergic children were compared with 69 children with a rheumatological disease while 37 peanut-allergic adults were compared with 42 adults with a rheumatological disease. The parents of peanut-allergic children, compared to the parents of children with a rheumatological disease, reported that their children had significantly more disruption in their daily activities. Furthermore, the parents of peanut-allergic children reported more impairment in the familial-social dimension of the IFQ. Conversely, adults with a chronic rheumatological disease reported more disruption in their family relations than peanut-allergic adults. CONCLUSION: Given the considerable disruption in daily activities and family relations reported by the parents of peanut-allergic children, accurate diagnosis of peanut allergy is essential. Our work should make health care professionals dealing with children with confirmed peanut allergy more aware of the support that these families may require. Furthermore, we hope to motivate food industries to offer more 'peanut free' products to decrease the dietary restrictions of these patients while minimizing their potential for accidental ingestion.

Global-local processing in schizophrenia: hemispheric asymmetry and symptom-specific interference.

The hypothesis of atypical functional hemispheric asymmetry in schizophrenia is tested using the directed global-local paradigm, a lateralizing measure of visual perception. Results indicate low error rates (< 2%) for schizophrenia and normal control groups, but longer response times for the schizophrenia group. In the normal group, detection speed of global and local forms did not differ. In contrast, the schizophrenia group responded significantly faster to local relative to global forms, which supports the asymmetry hypotheses of left hemisphere overactivity-right hemisphere underactivity in schizophrenia. The normal group exhibited a global interference effect (slowed response latency to the local target in the presence of a dissimilar global distractor). When the schizophrenia group was examined according to symptom type and severity, high positive symptom severity was associated with local interference (slowed response latency to the global target in the presence of dissimilar local distractors). Negative symptoms were not associated with interference from the competing local or global forms. Patients with a combination of high positive and low negative symptoms showed significantly greater local interference than patients with high negative and low positive symptoms. Interconnected temporal and frontal systems are postulated to contribute to this pattern of perceptual processing efficiency and distractibility in schizophrenia.

Neuropsychological functioning in migraine headache, nonheadache chronic pain, and mild traumatic brain injury patients.

There are conflicting reports in the literature concerning the neuropsychological functioning of migraine headache patients. The finding in some studies that migraineurs performed more poorly than healthy controls led to the hypothesis that chronic migraine may result in subtle but persistent cerebral dysfunction. Reports describing acute and between-headache neurophysiological disturbances in migraineurs lent support to this hypothesis. To elucidate the cognitive status of these patients, we administered a brief neuropsychological battery to 60 individuals with migraine headache (HA), nonheadache chronic pain (PAIN), or mild traumatic brain injury (MTBI). The PAIN group was included to test the hypothesis that cognitive difficulty in migraineurs might result from the discomfort, depression, medications, etc. often associated with chronic pain, rather than from brain dysfunction. The MTBI patients were considered a useful comparison for the migraineurs because their level of impairment was also expected to be mild, at worst. A MANOVA, with three cognitive index scores as the dependent variables, revealed that the three groups differed significantly. Follow-up contrasts demonstrated that the MTBI group was significantly more impaired on the memory index compared to the HA and PAIN groups, which did not differ from each other. The use of two different normative-based cutoffs to identify individuals who were impaired on the test battery revealed that the frequency of impairment within the two groups of pain patients, but not the MTBI patients, was within normal limits. Thus, the results did not support a link between migraine headache and cognitive impairment.

Dissociation of affect recognition and mood state from blunting in patients with schizophrenia.

The present study was designed to investigate the relationships between expression, perception, and experience of emotion in schizophrenic patients with and without affective blunting. Cognitive processing speed, emotional perception, and emotional experience were assessed in 25 schizophrenic patients grouped according to scores on a measure of overt emotional expression (Rating Scale for Emotional Blunting). Results showed dissociation of emotional expression from emotional perception and emotional experience. Blunted schizophrenic patients were no more impaired in the perception of emotion (Profile of Nonverbal Sensitivity) than non-blunted schizophrenic patients. In addition, groups did not differ in intensity of emotional experience as quantified on the self-report of arousal state (Positive and Negative Affect Scales). Accuracy of perception and reported experience of emotion did not differ between groups as a function of emotional valence. Cognitive processing speed (Symbol Digit Modalities Test; SDMT) was related to blunting score and to perception accuracy, although the SDMT did not differ between groups. Results are discussed in terms of a neuropathological basis for impairment of emotional expression.

Memory functioning in Lyme borreliosis.

BACKGROUND: To objectively measure memory functioning in patients with Lyme borreliosis and examine the relationship between subjective reports of memory dysfunction and actual impairment. METHOD: A prospective pretreatment study of patients with Lyme borreliosis (N = 21), a patient control group (osteomyelitis, N = 21), and healthy controls (N = 21) was conducted by using tests of verbal memory functioning (California Verbal Learning Test) and self-reported depression (Beck Depression Inventory-Cognitive Index), fatigue (Fatigue Severity Scale), and subjective ratings of memory abilities (Self-Rating Scale of Memory Functions). RESULTS: Patients with Lyme borreliosis performed worse than healthy controls on verbal memory testing, but did not perform significantly differently from patient controls. Lyme borreliosis patients reported increased fatigue, which was correlated with poorer memory performance. Although the Lyme borreliosis patients rated their memory as more impaired, subjective complaints were not correlated with objective memory scores. CONCLUSION: These findings suggest impaired memory performance is not specific to Lyme borreliosis and may be a result of evaluating cognitive functioning in patients with physical illness and somatic complaints. Fatigue is a prominent presenting complaint in patients with Lyme borreliosis and needs to be controlled for since it is known to influence neuropsychological performance. Subjective complaints are not correlated with objective memory assessment, so self-report of memory impairment should not be the criterion for inclusion in studies investigating cognitive manifestations of Lyme borreliosis.

When a baby dies: rights of the baby and parents.

The Rights of Parents When a Baby Dies and Rights of the Baby were developed by the Perinatal Bereavement Team at Women's College in Toronto, Canada. With permission, the National Office of SHARE: Pregnancy and Infant Loss Support, Inc. has revised and expanded these documents for distribution within the United States. The Rights are intended to help caregivers and institutions provide parents with information about their options regarding the death of their baby and allow them time and support for decision making.