An In Depth Analyses of Specific Language Impairment as Compared to Other Developmental Disorders

Specific language impairment (SLI), defined as a disproportionate difficulty in learning language despite having normal hearing, intelligence, and no known neurological or emotional impairment, has been shown to share similar cognitive characteristics with individuals with attention deficit hyperactive disorder (ADHD). However, little research has investigated the dissimilarities in these two different developmental disorders. Children with SLI also show many similar symptoms with individuals diagnosed with dyslexia. The aim of these studies is to get a better understanding of cognitive differences between SLI and ADHD, and the cognitive similarities between SLI and dyslexia. Tests of both verbal and non-verbal measures of working memory, IQ, and academic performance were administered to all groups. It was hypothesized that children with SLI would perform worse on verbal measures due to their language deficits but perform better on non-verbal measures than children with ADHD. It was also predicted that children with SLI will perform similarly, but worse than children with dyslexia. Results from the SLI/ADHD experiment confirm this pattern: children with SLI performed poorer than children with ADHD on all verbal cognitive measures. When looking at the non-verbal measures of abilities, the SLI group outperformed the ADHD group on working memory and IQ scores but not academic performance scores. Results from the SLI/Dyslexia experiment also confirmed what was predicted. Children with dyslexia outperformed their SLI counterparts on all cognitive measures. A possible explanation for these finding is that there are fewer classroom-based programs designed specifically to support children with SLI

Working with consumers who hear voices: The experience of early career nurses in mental health services in Australia

© 2018 Australian College of Mental Health Nurses Inc. Mental health consumers who hear voices frequently experience distress and express a desire to discuss their voice-hearing experience. Nurses do not regularly demonstrate a willingness to engage in such discussions. With the introduction of educational strategies that develop empathy and an understanding of voice-hearing experiences, it is anticipated that early career nurses will be able to translate such understanding into their professional nursing practice. To explore early career nurses’ understanding of providing care to mental health consumers who hear voices, a qualitative exploratory descriptive study was conducted in which nine early career Registered Nurses were interviewed regarding their experiences of caring for people who hear voices. Thematic analysis was employed to analyse the data and generate themes. Participants reported difficulty in developing relationships with consumers who hear voices, due to a workplace culture that was focussed on risk and lacking professional support. Nurses need specific education to develop the skills necessary to respond to consumers who hear voices and engage in dialogue that assists consumers to relate to the voices in a meaningful way. However, for this to succeed in practice, changes need to be supported by addressing the cultural barriers, such as risk-focussed environments, that prevent nurses implementing best practice

A phase 1 trial dose-escalation study of tipifarnib on a week-on, week-off schedule in relapsed, refractory or high-risk myeloid leukemia.

Inhibition of farnesyltransferase (FT) activity has been associated with in vitro and in vivo anti-leukemia activity. We report the results of a phase 1 dose-escalation study of tipifarnib, an oral FT inhibitor, in patients with relapsed, refractory or newly diagnosed (if over age 70) acute myelogenous leukemia (AML), on a week-on, week-off schedule. Forty-four patients were enrolled, two patients were newly diagnosed, and the rest were relapsed or refractory to previous treatment, with a median age of 61 (range 33-79). The maximum tolerated dose was determined to be 1200 mg given orally twice daily (b.i.d.) on this schedule. Cycle 1 dose-limiting toxicities were hepatic and renal. There were three complete remissions seen, two at the 1200 mg b.i.d. dose and one at the 1000 mg b.i.d. dose, with minor responses seen at the 1400 mg b.i.d. dose level. Pharmacokinetic studies performed at doses of 1400 mg b.i.d. showed linear behavior with minimal accumulation between days 1-5. Tipifarnib administered on a week-on, week-off schedule shows activity at higher doses, and represents an option for future clinical trials in AML

Presentations: from Kac-Moody groups to profinite and back

We go back and forth between, on the one hand, presentations of arithmetic and Kac-Moody groups and, on the other hand, presentations of profinite groups, deducing along the way new results on both

Sports injuries in adults: overview of clinical examination and management

A wide variety of anatomical structures can be involved in a sports injury. To return to play as soon as possible is of utmost importance to an athlete, and in order to achieve this, a correct, all-inclusive diagnosis, a well-focused treatment plan, and a management plan that strives to offer protection are essential. This article aims to give an overview of acute and overuse (chronic) sports injuries in adults, the approach to an accurate diagnosis and the management strategies that are available. A literature review was conducted of scientific journals, text and internet material, including a Medline and PubMed search. Literature was selected for its in-depth data and well-researched information. Key search terms included "acute and overuse injuries", as well as "sports injuries diagnosis and management" to address current and relevant scientific data on the examination and management of sports injuries in adults. The literature review indicated that sports injuries (both acute and overuse) are increasing in number due to the growing interest in physical activity and sport, as well as the enhanced intensity of training programmes. Adults are vulnerable to both types of sports injuries, and the age of occurrence of overuse injuries varies in competitive and non-competitive athletes. The importance of making an accurate diagnosis cannot be overemphasised. To assist the clinician in making an accurate diagnosis, a comprehensive history, physical examination and appropriate special investigations are mandatory. Familiarity with the demands of the athlete's sport may also prove useful. The approach to the management of acute and overuse injuries differs, with the emphasis in acute injuries being on treating the effect (torn, broken, displaced) and in chronic injuries on treating the cause (intrinsic or extrinsic). There have been numerous advances in the management of sports injuries, however further research is still warranted in this area. Follow-up articles will focus more in-depth on specifics with regard to clinical examination, special investigations and management options

PREDICT: a method for inferring novel drug indications with application to personalized medicine

The authors present a new method, PREDICT, for the large-scale prediction of drug indications, and demonstrate its use on both approved drugs and novel molecules. They also provide a proof-of-concept for its potential utility in predicting patient-specific medications

Identifying metabolites by integrating metabolome databases with mass spectrometry cheminformatics.

Novel metabolites distinct from canonical pathways can be identified through the integration of three cheminformatics tools: BinVestigate, which queries the BinBase gas chromatography-mass spectrometry (GC-MS) metabolome database to match unknowns with biological metadata across over 110,000 samples; MS-DIAL 2.0, a software tool for chromatographic deconvolution of high-resolution GC-MS or liquid chromatography-mass spectrometry (LC-MS); and MS-FINDER 2.0, a structure-elucidation program that uses a combination of 14 metabolome databases in addition to an enzyme promiscuity library. We showcase our workflow by annotating N-methyl-uridine monophosphate (UMP), lysomonogalactosyl-monopalmitin, N-methylalanine, and two propofol derivatives

An exfoliation and enrichment strategy results in improved transcriptional profiles when compared to matched formalin fixed samples

<p>Abstract</p> <p>Background</p> <p>Identifying the influence formalin fixation has on RNA integrity and recovery from clinical tissue specimens is integral to determining the utility of using archival tissue blocks in future molecular studies. For clinical material, the current gold standard is unfixed tissue that has been snap frozen. Fixed and frozen tissue however, both require laser capture microdissection to select for a specific cell population to study. The recent development of a sampling method capable of obtaining a viable, enriched cell population represents an alternative option in procuring cells from clinical material for molecular research purposes. The expression profiles of cells obtained by using this procurement approach, in conjunction with the profiles from cells laser capture microdissected from frozen tissue sections, were compared to the expression profiles from formalin fixed cells to determine the influence fixation has on expression profiles in clinical material.</p> <p>Methods</p> <p>Triplicate samples of non-neoplastic colonic epithelial cells were recovered from a hemicolectomy specimen using three different procurement methods from the same originating site: 1) an exfoliation and enrichment strategy 2) laser capture microdissection from formalin fixed tissue and 3) laser capture microdissection from frozen tissue. Parameters currently in use to assess RNA integrity were utilized to assess the quality of recovered RNA. Additionally, an expression microarray was performed on each sample to assess the influence each procurement technique had on RNA recovery and degradation.</p> <p>Results</p> <p>The exfoliation/enrichment strategy was quantitatively and qualitatively superior to tissue that was formalin fixed. Fixation negatively influenced the expression profile of the formalin fixed group compared to both the frozen and exfoliated/enrichment groups.</p> <p>Conclusion</p> <p>The exfoliation/enrichment technique represents a superior alternative in tissue procurement and RNA recovery relative to formalin fixed tissue. None of the deleterious effects associated with formalin fixation are encountered in the exfoliated/enriched samples because of the absence of its use in this protocol. The exfoliation/enrichment technique also represents an economical alternative that will yield comparable results to cells enriched by laser capture microdissection from frozen tissue sections.</p

Case report: a unique pediatric case of a primary CD8 expressing ALK-1 positive anaplastic large cell lymphoma of skeletal muscle

Primary involvement of skeletal muscle is a very rare event in ALK-1 positive anaplastic large cell lymphoma (ALCL). We describe a case of a 10-year old boy presenting with a three week history of pain and a palpable firm swelling at the dorsal aspect of the left thigh. Histological examination of the lesion revealed a tumoral and diffuse polymorphic infiltration of the muscle by large lymphoid cells. Tumor cells displayed eccentric, lobulated "horse shoe" or "kidney-shape" nuclei. The cells showed immunohistochemical positivity for CD30, ALK-1, CD2, CD3, CD7, CD8, and Perforin. Fluorescence in situ hybridization analysis revealed a characteristic rearrangement of the ALK-1 gene in 2p23 leading to the diagnosis of ALK-1 positive ALCL. Chemotherapy according to the ALCL-99-NHL-BFM protocol was initiated and resulted in a complete remission after two cycles. This case illustrates the unusual presentation of a pediatric ALCL in soft tissue with a good response to chemotherapy

Primary Results From the Understanding Outcomes With the S-ICD in Primary Prevention Patients With Low Ejection Fraction (UNTOUCHED) Trial

BACKGROUND: The subcutaneous (S) implantable cardioverter-defibrillator (ICD) is safe and effective for sudden cardiac death prevention. However, patients in previous S-ICD studies had fewer comorbidities, had less left ventricular dysfunction, and received more inappropriate shocks (IAS) than in typical transvenous ICD trials. The UNTOUCHED trial (Understanding Outcomes With the S-ICD in Primary Prevention Patients With Low Ejection Fraction) was designed to evaluate the IAS rate in a more typical, contemporary ICD patient population implanted with the S-ICD using standardized programming and enhanced discrimination algorithms. METHODS: Primary prevention patients with left ventricular ejection fraction ≤35% and no pacing indications were included. Generation 2 or 3 S-ICD devices were implanted and programmed with rate-based therapy delivery for rates ≥250 beats per minute and morphology discrimination for rates ≥200 and <250 beats per minute. Patients were followed for 18 months. The primary end point was the IAS-free rate compared with a 91.6% performance goal, derived from the results for the ICD-only patients in the MADIT-RIT study (Multicenter Automatic Defibrillator Implantation Trial-Reduce Inappropriate Therapy). Kaplan-Meier analyses were performed to evaluate event-free rates for IAS, all-cause shock, and complications. Multivariable proportional hazard analysis was performed to determine predictors of end points. RESULTS: S-ICD implant was attempted in 1116 patients, and 1111 patients were included in postimplant follow-up analysis. The cohort had a mean age of 55.8±12.4 years, 25.6% were women, 23.4% were Black, 53.5% had ischemic heart disease, 87.7% had symptomatic heart failure, and the mean left ventricular ejection fraction was 26.4±5.8%. Eighteen-month freedom from IAS was 95.9% (lower confidence limit, 94.8%). Predictors of reduced incidence of IAS were implanting the most recent generation of device, using the 3-incision technique, no history of atrial fibrillation, and ischemic cause. The 18-month all-cause shock-free rate was 90.6% (lower confidence limit, 89.0%), meeting the prespecified performance goal of 85.8%. Conversion success rate for appropriate, discrete episodes was 98.4%. Complication-free rate at 18 months was 92.7%. CONCLUSIONS: This study demonstrates high efficacy and safety with contemporary S-ICD devices and programming despite the relatively high incidence of comorbidities in comparison with earlier S-ICD trials. The inappropriate shock rate (3.1% at 1 year) is the lowest reported for the S-ICD and lower than many transvenous ICD studies using contemporary programming to reduce IAS. Registration: URL: https://www.clinicaltrials.gov; Unique identifier: NCT02433379