26085 Key efficacy and safety of apremilast in patients with mild to moderate plaque psoriasis in the phase 3 ADVANCE trial

Background: In ADVANCE, apremilast 30 mg BID (APR) demonstrated efficacy in mild-to-moderate psoriasis vs placebo (PBO). We report subgroup analyses by baseline psoriasis-involved BSA (≤5%, \u3e5%). Methods: Biologic-naive adults with mild-to-moderate psoriasis (sPGA 2-3, BSA 2%-15%, PASI 2-15) inadequately controlled with or intolerant to ≥1 topical were randomized to APR or PBO for 16 weeks. At Week 16, endpoints were compared between treatment groups and by baseline BSA. Results: At baseline, 284 patients had BSA ≤5% (APR: 143; PBO: 141); 311 had BSA \u3e5% (APR: 154; PBO: 157). Overall, a greater proportion of APR patients achieved the primary endpoint, sPGA response (score 0/1 [clear/almost clear] with ≥2-point reduction at Week 16) vs PBO (21.6% vs 4.1%, P 5%: 54.6% vs 14.9%, P 5%: 45.4% vs 17.6%, P 5%: 50.6% vs 19.2%, P 5%: 11.0 vs 10.0 DLQI 5-point improvement (baseline DLQI \u3e5): - BSA≤5%: 56.6% vs 31.2%, P =.0002 - BSA\u3e5%: 64.4% vs 36.4%, P ˂.0001. Conclusions: Greater proportions of patients achieved efficacy outcomes and greater improvements in QOL with APR vs PBO. Comparable improvements were observed between mild and moderate subgroups

Bis(\u3cem\u3eN\u3c/em\u3e-amidinohydrazones) and \u3cem\u3eN\u3c/em\u3e-(amidino)-\u3cem\u3eN\u3c/em\u3e\u27-aryl-bishydrazones: New Classes of Antibacterial/Antifungal Agents

The emergence of multidrug-resistant bacterial and fungal strains poses a threat to human health that requires the design and synthesis of new classes of antimicr obial agents. We evaluated bis(N-amidinohydrazones) and N-(amidino)-N\u27-aryl-bishydrazones for their antibacterial and antifungal activities against panels of Gram-positive/Gram-negative bacteria as well as fungi. We investigated their potential to develop resistance against both bacteria and fungi by a multi-step, resistance-selection method, explored their potential to induce the production of reactive oxygen species, and assessed their toxicity. In summary, we found that these compounds exhibited broad-spectrum antibacterial and antifungal activities against most of the tested strains with minimum inhibitory concentration (MIC) values ranging from \u3c 0.5- \u3e 500 μM against bacteria and 1.0- \u3e 31.3 μg/mL against fungi; and in most cases, they exhibited either superior or similar antimicrobial activity compared to those of the standard drugs used in the clinic. We also observed minimal emergence of drug resistance to these newly synthesized compounds by bacteria and fungi even after 15 passages, and we found weak to moderate inhibition of the human Ether-à-go-go-related gene (hERG) channel with acceptable IC50 values ranging from 1.12-3.29 μM. Overall, these studies sh ow that bis(N-amidinohydrazones) and N-(amidino)-N\u27-aryl-bishydrazones are potentially promising scaffolds for the discovery of novel antibacterial and antifungal agents

Four-point correlators with higher weight superconformal primaries in the AdS/CFT Correspondence

The four-point correlation function of two 1/2 BPS primaries of conformal weight $\Delta=2$ and two 1/2-BPS primaries of conformal weight $\Delta=n$ is calculated in the large 't Hooft, large $N$ limit. These operators are dual to Kaluza-Klein supergravity fields $s_k$ with masses $m^2=-4$ and $m^2=n(n-4)$. Given that the existing formalism for evaluating sums of products of SO(6) tensors that determine the effective couplings is only suitable for primaries with small conformal dimensions, we make us of an alternative formalism based on harmonic polynomials introduced by Dolan and Osborn. We then show that the supergravity lagrangian relevant to the computation is of sigma-model type (i.e., the four-derivative couplings vanish) and that the final result for the connected amplitude splits into a free and an interacting part, as expected on general grounds.Comment: 31 pages, 4 figure

Evidence-based medicine among internal medicine residents in a community hospital program using smart phones

BACKGROUND: This study implemented and evaluated a point-of-care, wireless Internet access using smart phones for information retrieval during daily clinical rounds and academic activities of internal medicine residents in a community hospital. We did the project to assess the feasibility of using smart phones as an alternative to reach online medical resources because we were unable to find previous studies of this type. In addition, we wanted to learn what Web-based information resources internal medicine residents were using and whether providing bedside, real-time access to medical information would be perceived useful for patient care and academic activities. METHODS: We equipped the medical teams in the hospital wards with smart phones (mobile phone/PDA hybrid devices) to provide immediate access to evidence-based resources developed at the National Library of Medicine as well as to other medical Websites. The emphasis of this project was to measure the convenience and feasibility of real-time access to current medical literature using smart phones. RESULTS: The smart phones provided real-time mobile access to medical literature during daily rounds and clinical activities in the hospital. Physicians found these devices easy to use. A post-study survey showed that the information retrieved was perceived to be useful for patient care and academic activities. CONCLUSION: In community hospitals and ambulatory clinics without wireless networks where the majority of physicians work, real-time access to current medical literature may be achieved through smart phones. Immediate availability of reliable and updated information obtained from authoritative sources on the Web makes evidence-based practice in a community hospital a reality

The Grizzly, February 17, 1997

Window Shopping Without the Glass • Ursinus Celebrates Diversity Week • Students Benefit from Internships • Study Abroad: They Don\u27t Call \u27Em Deadlines For Nothing • Campus Apathy on the Issue of Diversity • And the Spirit Moved Them • Caplan Addresses Ethical Issues • Dr. Scott Landis\u27 Resignation Announced • So This is What Security Does: Ursinus\u27 Security Log Returns • Opinion: Greek Speaks Out; Read This if you Think Pledging is Dumb; Come Catch a Square; Perspective from Scotland; Faces of Silence • Defend Yourself! • Keep the Tutorial Program Alive! • Wrestling Bears Win Conference Championship • Women\u27s Basketball Nets Three More Wins • Men\u27s Basketball Drops Two • Gymnasts Leap to Two More Winshttps://digitalcommons.ursinus.edu/grizzlynews/1397/thumbnail.jp

Genome-wide analyses for personality traits identify six genomic loci and show correlations with psychiatric disorders

Personality is influenced by genetic and environmental factors1 and associated with mental health. However, the underlying genetic determinants are largely unknown. We identified six genetic loci, including five novel loci2,3, significantly associated with personality traits in a meta-analysis of genome-wide association studies (N = 123,132–260,861). Of these genomewide significant loci, extraversion was associated with variants in WSCD2 and near PCDH15, and neuroticism with variants on chromosome 8p23.1 and in L3MBTL2. We performed a principal component analysis to extract major dimensions underlying genetic variations among five personality traits and six psychiatric disorders (N = 5,422–18,759). The first genetic dimension separated personality traits and psychiatric disorders, except that neuroticism and openness to experience were clustered with the disorders. High genetic correlations were found between extraversion and attention-deficit– hyperactivity disorder (ADHD) and between openness and schizophrenia and bipolar disorder. The second genetic dimension was closely aligned with extraversion–introversion and grouped neuroticism with internalizing psychopathology (e.g., depression or anxiety)

Rare copy number variants: a point of rarity in genetic risk for bipolar disorder and schizophrenia

Context: Recent studies suggest that copy number variation in the human genome is extensive and may play an important role in susceptibility to disease, including neuropsychiatric disorders such as schizophrenia and autism. The possible involvement of copy number variants (CNVs) in bipolar disorder has received little attention to date. Objectives: To determine whether large (>100 000 base pairs) and rare (found in <1% of the population) CNVs are associated with susceptibility to bipolar disorder and to compare with findings in schizophrenia. Design: A genome-wide survey of large, rare CNVs in a case-control sample using a high-density microarray. Setting: The Wellcome Trust Case Control Consortium. Participants: There were 1697 cases of bipolar disorder and 2806 nonpsychiatric controls. All participants were white UK residents. Main Outcome Measures: Overall load of CNVs and presence of rare CNVs. Results: The burden of CNVs in bipolar disorder was not increased compared with controls and was significantly less than in schizophrenia cases. The CNVs previously implicated in the etiology of schizophrenia were not more common in cases with bipolar disorder. Conclusions: Schizophrenia and bipolar disorder differ with respect to CNV burden in general and association with specific CNVs in particular. Our data are consistent with the possibility that possession of large, rare deletions may modify the phenotype in those at risk of psychosis: those possessing such events are more likely to be diagnosed as having schizophrenia, and those without them are more likely to be diagnosed as having bipolar disorder

A cross sectional evaluation of an alcohol intervention targeting young university students

BACKGROUND: Hazardous drinking has been found to be higher among young university students compared to their non-university peers. Although young university students are exposed to new and exciting experiences, including greater availability and emphasis on social functions involving alcohol there are few multi strategy comprehensive interventions aimed at reducing alcohol-related harms. METHODS: Random cross sectional online surveys were administered to 18-24 year old students studying at the main campus of a large metropolitan university in Perth, Western Australia. Prior to the completion of the second survey an alcohol intervention was implemented on campus. Completed surveys were received from 2465 (Baseline; T1) and 2422 (Post Year 1: T2) students. Students who consumed alcohol in the past 12 months were categorised as low risk or hazardous drinkers using the Alcohol Use Disorders Identification Test (AUDIT). Due to the cross sectional nature of the two samples two-tailed two-proportion z-test and two sample t-tests were employed to determine statistical significance between the two time periods for categorical and continuous variables respectively. RESULTS: At T1 and T2 89.1 % and 87.2 % of the total sample reported drinking alcohol in the past month respectively. Hazardous levels of alcohol consumption reduced slightly between T1 (39.7 %) and T2 (38 %). In both time periods hazardous drinkers reported significantly higher mean scores for experienced harm, second-hand harm and witnessed harm scores compared to low risk drinkers (p &lt;0.001). Hazardous drinkers were significantly more likely to experience academic problems due to their alcohol consumption and to report more positive alcohol expectations than low risk drinkers at both time periods (p &lt;0.001). CONCLUSIONS: Harms and problems for students who report hazardous drinking are of concern and efforts should be made to ensure integrated and targeted strategies reach higher risk students and focus on specific issues such as driving while intoxicated and alcohol related unplanned sexual activity. However there is also a need for universal strategies targeting all students and low risk drinkers as they too are exposed to alcohol harms within the drinking and social environment. Changing the culture of the university environment is a long term aim and to effect change a sustained combination of organisational actions, partnerships and educational actions is required

Individual common variants exert weak effects on the risk for autism spectrum disorders.

While it is apparent that rare variation can play an important role in the genetic architecture of autism spectrum disorders (ASDs), the contribution of common variation to the risk of developing ASD is less clear. To produce a more comprehensive picture, we report Stage 2 of the Autism Genome Project genome-wide association study, adding 1301 ASD families and bringing the total to 2705 families analysed (Stages 1 and 2). In addition to evaluating the association of individual single nucleotide polymorphisms (SNPs), we also sought evidence that common variants, en masse, might affect the risk. Despite genotyping over a million SNPs covering the genome, no single SNP shows significant association with ASD or selected phenotypes at a genome-wide level. The SNP that achieves the smallest P-value from secondary analyses is rs1718101. It falls in CNTNAP2, a gene previously implicated in susceptibility for ASD. This SNP also shows modest association with age of word/phrase acquisition in ASD subjects, of interest because features of language development are also associated with other variation in CNTNAP2. In contrast, allele scores derived from the transmission of common alleles to Stage 1 cases significantly predict case status in the independent Stage 2 sample. Despite being significant, the variance explained by these allele scores was small (Vm&lt; 1%). Based on results from individual SNPs and their en masse effect on risk, as inferred from the allele score results, it is reasonable to conclude that common variants affect the risk for ASD but their individual effects are modest

Does physiotherapy reduce the incidence of postoperative complications in patients following pulmonary resection via thoracotomy? a protocol for a randomised controlled trial

Background: Postoperative pulmonary and shoulder complications are important causes of postoperative morbidity following thoracotomy. While physiotherapy aims to prevent or minimise these complications, currently there are no randomised controlled trials to support or refute effectiveness of physiotherapy in this setting. Methods/Design: This single blind randomised controlled trial aims to recruit 184 patients following lung resection via open thoracotomy. All subjects will receive a preoperative physiotherapy information booklet and following surgery will be randomly allocated to a Treatment Group receiving postoperative physiotherapy or a Control Group receiving standard care nursing and medical interventions but no physiotherapy. The Treatment Group will receive a standardised daily physiotherapy programme to prevent respiratory and musculoskeletal complications. On discharge Treatment Group subjects will receive an exercise programme and exercise diary to complete. The primary outcome measure is the incidence of postoperative pulmonary complications, which will be determined on a daily basis whilst the patient is in hospital by a blinded assessor. Secondary outcome measures are the length of postoperative hospital stay, severity of pain, shoulder function as measured by the self-reported shoulder pain and disability index, and quality of life measured by the Medical Outcomes Study Short Form 36 v2 New Zealand standard version. Pain, shoulder function and quality of life will be measured at baseline, on discharge from hospital, one month and three months postoperatively. Additionally a subgroup of subjects will have measurement of shoulder range of movement and muscle strength by a blinded assessor. Discussion: Results from this study will contribute to the increasing volume of evidence regarding the effectiveness of physiotherapy following major surgery and will guide physiotherapists in their interventions for patients following thoracotomy. Trial registration: The study protocol is registered with the Australian and New Zealand Clinical Trials registry (ANZCTRN12605000201673)