Test of Lepton-Flavor Universality in B→K

We present a measurement of R_{K^{*}}, the branching fraction ratio B(B→K^{*}µ^{+}µ^{-})/B(B→K^{*}e^{+}e^{-}), for both charged and neutral B mesons. The ratio for the charged case R_{K^{*+}} is the first measurement ever performed. In addition, we report absolute branching fractions for the individual modes in bins of the squared dilepton invariant mass q^{2}. The analysis is based on a data sample of 711 fb^{-1}, containing 772×10^{6} BB[over ¯] events, recorded at the ϒ(4S) resonance with the Belle detector at the KEKB asymmetric-energy e^{+}e^{-} collider. The obtained results are consistent with standard model expectations.

First Measurements of Absolute Branching Fractions of the Ξ_{c}

We present the first measurements of absolute branching fractions of Ξ_{c}^{0} decays into Ξ^{-}π^{+}, ΛK^{-}π^{+}, and pK^{-}K^{-}π^{+} final states. The measurements are made using a dataset comprising (772±11)×10^{6} BB[over ¯] pairs collected at the ϒ(4S) resonance with the Belle detector at the KEKB e^{+}e^{-} collider. We first measure the absolute branching fraction for B^{-}→Λ[over ¯]_{c}^{-}Ξ_{c}^{0} using a missing-mass technique; the result is B(B^{-}→Λ[over ¯]_{c}^{-}Ξ_{c}^{0})=(9.51±2.10±0.88)×10^{-4}. We subsequently measure the product branching fractions B(B^{-}→Λ[over ¯]_{c}^{-}Ξ_{c}^{0})B(Ξ_{c}^{0}→Ξ^{-}π^{+}), B(B^{-}→Λ[over ¯]_{c}^{-}Ξ_{c}^{0})B(Ξ_{c}^{0}→ΛK^{-}π^{+}), and B(B^{-}→Λ[over ¯]_{c}^{-}Ξ_{c}^{0})B(Ξ_{c}^{0}→pK^{-}K^{-}π^{+}) with improved precision. Dividing these product branching fractions by the result for B^{-}→Λ[over ¯]_{c}^{-}Ξ_{c}^{0} yields the following branching fractions: B(Ξ_{c}^{0}→Ξ^{-}π^{+})=(1.80±0.50±0.14)%, B(Ξ_{c}^{0}→ΛK^{-}π^{+})=(1.17±0.37±0.09)%, and B(Ξ_{c}^{0}→pK^{-}K^{-}π^{+})=(0.58±0.23±0.05)%. For the above branching fractions, the first uncertainties are statistical and the second are systematic. Our result for B(Ξ_{c}^{0}→Ξ^{-}π^{+}) can be combined with Ξ_{c}^{0} branching fractions measured relative to Ξ_{c}^{0}→Ξ^{-}π^{+} to yield other absolute Ξ_{c}^{0} branching fractions.

Search for B

We report the results of a search for the rare, purely leptonic decay B^{-}→µ^{-}ν[over ¯]_{µ} performed with a 711 fb^{-1} data sample that contains 772×10^{6} BB[over ¯] pairs, collected near the ϒ(4S) resonance with the Belle detector at the KEKB asymmetric-energy e^{+}e^{-} collider. The signal events are selected based on the presence of a high momentum muon and the topology of the rest of the event showing properties of a generic B-meson decay, as well as the missing energy and momentum being consistent with the hypothesis of a neutrino from the signal decay. We find a 2.4 standard deviation excess above background including systematic uncertainties, which corresponds to a branching fraction of B(B^{-}→µ^{-}ν[over ¯]_{µ})=(6.46±2.22±1.60)×10^{-7} or a frequentist 90% confidence level interval on the B^{-}→µ^{-}ν[over ¯]_{µ} branching fraction of [2.9,10.7]×10^{-7}.

First Observation of the Doubly Cabibbo-Suppressed Decay of a Charmed Baryon: Λ_{c}

We report the first observation of the decay Λ_{c}^{+}→pK^{+}π^{-} using a 980 fb^{-1} data sample collected by the Belle detector at the KEKB asymmetric-energy e^{+}e^{-} collider. This is the first observation of a doubly Cabibbo-suppressed decay of a charmed baryon. We measure the branching ratio of this decay with respect to its Cabibbo-favored counterpart to be B(Λ_{c}^{+}→pK^{+}π^{-})/B(Λ_{c}^{+}→pK^{-}π^{+})=(2.35±0.27±0.21)×10^{-3}, where the uncertainties are statistical and systematic, respectively.

Observation of the Decay B_{s}

We measure the decay B_{s}^{0}→K^{0}K[over ¯]^{0} using data collected at the ϒ(5S) resonance with the Belle detector at the KEKB e^{+}e^{-} collider. The data sample used corresponds to an integrated luminosity of 121.4 fb^{-1}. We measure a branching fraction B(B_{s}^{0}→K^{0}K[over ¯]^{0})=[19.6_{-5.1}^{+5.8}(stat)±1.0(syst)±2.0(N_{B_{s}^{0}B[over ¯]_{s}^{0}})]×10^{-6} with a significance of 5.1 standard deviations. This measurement constitutes the first observation of this decay.

Energy Scan of the e

Using data collected with the Belle detector at the KEKB asymmetric-energy e^{+}e^{-} collider, we measure the energy dependence of the e^{+}e^{-}→h_{b}(nP)π^{+}π^{-} (n=1, 2) cross sections from thresholds up to 11.02 GeV. We find clear ϒ(10860) and ϒ(11020) peaks with little or no continuum contribution. We study the resonant substructure of the ϒ(11020)→h_{b}(nP)π^{+}π^{-} transitions and find evidence that they proceed entirely via the intermediate isovector states Z_{b}(10610) and Z_{b}(10650). The relative fraction of these states is loosely constrained by the current data: The hypothesis that only Z_{b}(10610) is produced is excluded at the level of 3.3 standard deviations, while the hypothesis that only Z_{b}(10650) is produced is not excluded at a significant level.

Observation of B

We report the first observation of the decays B^{0}→pΛ[over ¯]D^{(*)-}. The data sample of 711 fb^{-1} used in this analysis corresponds to 772×10^{6} BB[over ¯] pairs, collected at the ϒ(4S) resonance by the Belle detector at the KEKB asymmetric-energy e^{+}e^{-} collider. We observe 19.8σ and 10.8σ excesses of events for the two decay modes and measure the branching fractions of B^{0}→pΛ[over ¯]D^{-} and B^{0}→pΛ[over ¯]D^{*-} to be (25.1±2.6±3.5)×10^{-6} and (33.6±6.3±4.4)×10^{-6}, respectively, where the first uncertainties are statistical and the second are systematic. These results are not compatible with the predictions based on the generalized factorization approach. In addition, a threshold enhancement in the dibaryon (pΛ[over ¯]) system is observed, consistent with that observed in similar B decays.

Mutation-independent rescue of a novel mouse model of Retinitis Pigmentosa.

Retinitis Pigmentosa (RP) is the leading cause of inherited blindness in the developed world, affecting approximately 1 in 3000 individuals. Although there is currently no cure for RP, the genetic pathology has been well established. In this study, we developed a novel mouse model of RP (huRhoP347S) expressing a pathogenic human rhodopsin gene with a Pro347Ser (P347S) mutation on a rhodopsin knockout background. These mice undergo severe retinal degeneration at 1 month of age. In contrast to prior studies, this model was administered a gene therapy treatment at 19 days postnata. We evaluated several self-complementary adeno-associated virus (AAV) serotypes for photoreceptor tropism, including scAAV2/2, scAAV2/5, scAAV2/6.2 and scAAV2/9, and found that scAAV2/9 transduced photoreceptors with greater efficiency and expression than other vectors. We engineered an scAAV2/9 vector to contain a microRNA sequence specifically targeting the human rhodopsin gene and demonstrated its ability to silence rhodopsin by 60.2±8.2% in vitro. In addition, we constructed an scAAV2/9 vector to contain a replacement 'codon-modified' rhodopsin transgene (RhoR2) that was resistant to degradation by the microRNA. We found that delivery of the RhoR2 by scAAV2/9 is capable of restoring vision to rhodopsin knockout mice, and rescuing our novel transgenic huRhoP347S mouse model of dominant RP. Average a-wave responses of RhoR2-injected eyes were 1.8-fold higher than those of control-injected eyes. We found that delivery of the microRNA and replacement rhodopsin in a 1:2 ratio produced an average electroretinography (ERG) a-wave response of 17.4±2.9 compared to 6.5±2.8 µV for eyes injected with negative control virus.

Mechanisms of functional improvement in a 2-year trial of cognitive enhancement therapy for early schizophrenia.

BACKGROUND: Cognitive rehabilitation has emerged as an effective treatment for addressing cognitive impairments and functional disability in schizophrenia; however, the degree to which changes in various social and non-social cognitive processes translate into improved functioning during treatment remains unclear. This research sought to identify the neurocognitive and social-cognitive mechanisms of functional improvement during a 2-year trial of cognitive enhancement therapy (CET) for early-course schizophrenia. METHOD: Patients in the early course of schizophrenia were randomly assigned to CET (n=31) or an enriched supportive therapy control (n=27) and treated for up to 2 years. A comprehensive neurocognitive assessment battery and the Mayer-Salovey-Caruso Emotional Intelligence Test (MSCEIT) were completed annually, along with measures of functioning. Mediator analyses using mixed-effects growth models were conducted to examine the effects of neurocognitive and social-cognitive improvement on functional change. RESULTS: Improvements over 2 years in neurocognition and the emotion management branch of the MSCEIT were found to be significantly related to improved functional outcome in early-course schizophrenia patients. Neurocognitive improvement, primarily in executive functioning, and social-cognitive change in emotion management also mediated the robust effects of CET on functioning. CONCLUSIONS: Improvements in neurocognition and social cognition that result from cognitive rehabilitation are both significant mediators of functional improvement in early-course schizophrenia. Cognitive rehabilitation programs for schizophrenia may need to target deficits in both social and non-social cognition to achieve an optimal functional response.

Is prostate cancer stage migration continuing for black men in the PSA era?

BACKGROUND: In the United States, disease-specific mortality from prostate cancer (PC) is highest among black men. While the introduction of widespread PSA testing has been associated with a downward stage migration, whether this trend continues in the late PSA era and for black men is unknown. The objective of our study was to evaluate current PC stage migration patterns in the United States by race. METHODS: The Surveillance, Epidemiology and End Results (SEER) registry was queried to obtain all cases of PC reported between 2000 and 2013. Year of diagnosis was categorized into 2000-2003, 2004-2007, 2008-2010 and 2011-2013. Predictors of distant stage PC at diagnosis were determined using logistic regression adjusted for year of diagnosis, age at diagnosis, SEER region and race. RESULTS: A total of 791 184 PC cases were identified. The cohort comprised 78.9% (n=594 920) white and 14.1% (n=106 133) black men. The stage at diagnosis was 83.3% localized, 12.0% regional and 4.7% distant. Age-adjusted incidence demonstrated a steady decline for black men in all time groups while white men had a stable incidence of distant disease between 2000 and 2013. In univariate analysis, black men in the 2004-2007 (OR 0.86 (0.81-0.93)) and 2008-2010 cohorts (OR 0.85 (0.79-0.91)) were less likely to be diagnosed with metastatic PC as compared with the 2000-2003 baseline cohort. In multivariate analysis, the 2004-2007 black cohort was less likely to be diagnosed with distant PC (OR 0.90 (0.84-0.97)). This trend was not observed in white men who in multivariate analysis had an increased risk of distant PC in the 2004-2007 (OR 1.08 (1.04-1.11)), 2008-2010 (OR 1.22 (1.18-1.27)) and 2011-2013 (OR 1.65 (1.59-1.71)) groups. CONCLUSIONS: PC downward stage migration continues in black men but not in white men. Discontinuation of PSA-based screening for PC could disproportionately affect black men.

Family psychoeducation, social skills training, and maintenance chemotherapy in the aftercare treatment of schizophrenia. I. One-year effects of a controlled study on relapse and expressed emotion.

Relapse rates averaging 41% in the first year after discharge among schizophrenic patients receiving maintenance neuroleptic treatment led to the development of two disorder-relevant treatments: a patient-centered behavioral treatment and a psychoeducational family treatment. Following hospital admission, 103 patients residing in high expressed emotion (EE) households who met Research Diagnostic Criteria for schizophrenia or schizoaffective disorder were randomly assigned to a two-year aftercare study of family treatment and medication, social skills training and medication, their combination, or a drug-treated condition. First-year relapse rates among those exposed to treatment demonstrate a main effect for family treatment (19%), a main effect for social skills training (20%), and an additive effect for the combined conditions (0%) relative to controls (41%). Effects are explained, in part, by the absence of relapse in any household that changed from high to low EE. Only the combination of treatment sustains a remission in households that remain high in EE. Continuing study, however, suggests a delay of relapse rather than prevention.

Family psychoeducation, social skills training, and maintenance chemotherapy in the aftercare treatment of schizophrenia. II. Two-year effects of a controlled study on relapse and adjustment. Environmental-Personal Indicators in the Course of Schizophrenia (EPICS) Research Group.

We demonstrated earlier that a novel family psychoeducational approach and an individual social skills training approach designed for patients living in high-expressed emotion households each reduced schizophrenic relapse by one-half when compared with medication controls in the 1st year after hospital discharge. The combination of treatments resulted in no relapse. Results have now been obtained after 2 years of continuous treatment. By 24 months, a persistent and significant effect of family intervention on forestalling relapse was observed, but the effect of social skills training was lost late in the 2nd year. There was no additive effect on relapse that accrued to the combination of treatments. Beyond 2 years, however, the effect of family intervention was likely compromised as well. Treatment effects on the adjustment of survivors were circumscribed, due, in part, to study design characteristics. Effects generally favored the social skills-alone condition at 1 year and the family condition or combined family/social skills condition at 2 years.

Review article: the safety of therapeutic drugs in male inflammatory bowel disease patients wishing to conceive.

BACKGROUND: Many therapeutic drugs are used by patients with inflammatory bowel disease, often around the time of conception. The pregnancy outcomes of males and females exposed to these therapeutics needs to be examined and this information is necessary to counsel patients appropriately. AIM: To review the literature describing male infertility and inflammatory bowel disease to educate practitioners of the impact of inflammatory bowel disease on male reproduction and the impact of therapeutics on pregnancy outcomes. METHODS: We performed a PubMed search using the search terms 'male infertility,' 'Crohn's disease,' 'inflammatory bowel disease,' 'ulcerative colitis,' 'ciprofloxacin AND infertility,' 'metronidazole AND infertility,' 'sulfasalazine AND infertility,' 'azathioprine AND infertility,' 'methotrexate AND infertility,' 'ciclosporin AND infertility,' 'corticosteroids AND infertility,' 'infliximab AND male fertility,' 'infliximab AND infertility,' 'infliximab AND foetus,' 'infliximab AND paternal exposure' and 'infliximab AND sperm.' References from selected papers were reviewed and used if relevant. RESULTS: Over half of male patients with IBD have some degree of infertility, compared to 8-17% of the general population. Semen parameters including total count, motility and morphology may be adversely affected by therapeutics. IBD medications in males do not increase foetal risk with the possible exception of azathioprine and mercaptopurine; however, increased foetal risk is seen in other drugs if taken by female patients. CONCLUSIONS: It is recognised that male infertility is often impacted with therapeutic drugs used to treat inflammatory bowel disease; however, the effects of the paternal drug exposure at the time of conception and exposure in utero should be considered to counsel patients appropriately.

Three-year trials of personal therapy among schizophrenic patients living with or independent of family, I: Description of study and effects on relapse rates.

OBJECTIVE: The study of individual psychotherapeutic approaches to the treatment of schizophrenia has yielded equivocal findings, partly because of methodologic problems. Further, the ability of psychosocial treatments to prevent psychotic relapse appears to lessen over time. The authors' goal was to develop and test a demonstrably effective individual therapy for schizophrenia. METHOD: Using a study design that addressed previous methodologic issues, the authors evaluated personal therapy specifically designed to forestall late relapse in patients with schizophrenia. They evaluated the effectiveness of personal therapy over a period of 3 years after hospital discharge among 151 patients with schizophrenia or schizoaffective disorder diagnosed according to Research Diagnostic Criteria. The patients were randomly assigned to receive either personal therapy or contrasting therapies in one of two concurrent trials. One trial studied patients who were living with family (N = 97); the other studied patients who were living independent of family (N = 54). RESULTS: All of the patients had extensive psychiatric histories, but only 44 (29%) experienced recurrent psychotic episodes over the 3-year study period, and only 27 (18%) prematurely terminated the study; most of those who left the study were in the no-personal-therapy conditions. Among patients living with family, personal therapy was more effective than family and supportive therapies in preventing psychotic and affective relapse as well as noncompliance. However, among patients living independent of family, those who received personal therapy had significantly more psychotic decompensations than did those who received supportive therapy. CONCLUSIONS: Personal therapy had a positive effect on adverse outcomes among patients who lived with family. However, personal therapy increased the rate of psychotic relapse for patients living independent of family. The application of personal therapy might best be delayed until patients have achieved symptom and residential stability.

Three-year trials of personal therapy among schizophrenic patients living with or independent of family, II: Effects on adjustment of patients.

OBJECTIVE: Previous analyses of the personal and social adjustment of outpatients with schizophrenia have either relied on the assessment of unrepresentative patients who survived without relapse or used analyses that included relapse assessments, a potential confound when different rates of relapse existed among treatment conditions. The authors' goal was to conduct a study of the effects of personal therapy on outcome that was designed to take into consideration the effects of relapse. METHOD: They evaluated the effectiveness of personal therapy over 3 years after hospital discharge among 151 patients with schizophrenia or schizoaffective disorder. The patients were randomly assigned to receive personal therapy or contrasting therapies in one of two concurrent trials. One trial included patients who were living with family (N = 97); the other included patients who were living independent of family (N = 54). Patients were assessed at 6-month intervals over 3 years of treatment on measures of personal and social adjustment; patients who relapsed and restabilized and those who did not relapse were included. RESULTS: Personal therapy had positive effects on broad components of social adjustment (role performance) but had few differential effects on symptoms, and patients receiving personal therapy remained more anxious than patients who received family or supportive therapy. For patients who were living with family, personal therapy led to better outcomes in overall performance than did the other treatments. Although family therapy had only one positive effect on patients' social adjustment, the personal adjustment (residual symptoms) of patients who received family therapy appeared to improve more than that of patients receiving personal or supportive therapy. For patients not living with family, personal therapy was more successful than supportive therapy in improving work performance and relationships out of the home. Longitudinal effects of personal therapy on symptoms were similar to those of family and supportive therapies, particularly in the first 2 years, but personal therapy effect sizes increased over time on measures of social adjustment. CONCLUSIONS: Personal therapy has pervasive effects on the social adjustment of patients with schizophrenia that are independent of relapse prevention. Supportive therapy, with or without family intervention, produces adjustment effects that peak at 12 months after discharge and plateau thereafter. However, personal therapy, a definitive psychosocial intervention, continues to improve the social adjustment of patients in the second and third years after discharge. Brief treatment would appear to be less effective than a long-term, disorder-relevant intervention for schizophrenia.

Nicotinic alpha 7 receptors protect against glutamate neurotoxicity and neuronal ischemic damage.

The alpha7 receptor agonist dimethoxybenzylidene anabaseine (DMXB) protected rat neocortical neurons against excitotoxicity administered 24 h before, but not concomitantly with, NMDA. This action was blocked by nicotinic but not muscarinic antagonists. DMXB (1 mg/kg i.p.) also reduced infarct size in rats when injected 24 h before, but not during, focal ischemic insults. In a mecamylamine-sensitive manner, alpha7 receptors appear neuroprotective in non-apoptotic model.

Personal therapy: a disorder-relevant psychotherapy for schizophrenia.

While the long-term care of ambulatory schizophrenia patients requires highly effective interpersonal treatment skills among clinicians, there is little evidence to support an empirically validated individual psychotherapy of schizophrenia. Personal therapy (PT) attempts to address the apparent limitations of traditional psychotherapy by modifying the "model of the person" to accommodate an underlying pathophysiology, minimizing potential iatrogenic effects of maintenance antipsychotic medication, controlling sources of environmental provocation, and extending therapy to a time when crisis management has lessened and stabilization is better ensured. By means of graduated, internal coping strategies, PT attempts to provide a growing awareness of personal vulnerability, including the "internal cues" of affect dysregulation. The goals are to increase foresight through the accurate appraisal of emotional states, their appropriate expression, and assessment of the reciprocal response of others. The strategies are supplemented by phase-specific psychoeducation and behavior therapy techniques. Practical issues in the application of this new intervention are discussed. Preliminary observations from two samples of patients, one living with and the other living independent of family, suggest differential improvement over time among PT recipients.

Estrogens may reduce mortality and ischemic damage caused by middle cerebral artery occlusion in the female rat.

The present study was undertaken to determine if estrogens protect female rats from the neurodegenerative effects of middle cerebral artery (MCA) occlusion. The rats were ovariectomized and 7 or 8 days later various estrogen preparations were administered before or after MCA occlusion. Pretreatment with 17beta-estradiol (17beta-E2) or a brain-targeted 17beta-E2 chemical delivery system (CDS) decreased mortality from 65% in ovariectomized rats to 22% in 17beta-E2-treated and 16% in 17beta-E2 CDS-treated rats. This marked reduction in mortality was accompanied by a reduction in the ischemic area of the brain from 25.6+/-5.7% in the ovariectomized rats to 9.8+/-4% and 9.1+/-4.2% in the 17beta-E2-implanted and the 17beta-E2 CDS-treated rats, respectively. Similarly, pretreatment with the presumed inactive estrogen, 17alpha-estradiol, reduced mortality from 36 to 0% and reduced the ischemic area by 55 to 81%. When administered 40 or 90 minutes after MCA occlusion, 17beta-E2 CDS reduced the area of ischemia by 45 to 90% or 31%, respectively. In summary, the present study provides the first evidence that estrogens exert neuroprotective effects in an animal model of ischemia and suggests that estrogens may be a useful therapy to protect neurons against the neurodegenerative effects of stroke.

Free tissue transfer to extend the limits of limb salvage for lower extremity tissue loss.

BACKGROUND: The extent of tissue loss amenable to primary healing after revascularization is unknown. Salvage of limbs with large soft-tissue defects with exposed tendon, joint, or bone lies beyond the limits of conventional techniques. We report our results using free tissue transfer as an adjunct to lower extremity vascular reconstruction in patients with complex ischemic or infected wounds. METHODS: Retrospective chart review of patient and wound characteristics. RESULTS: From January 1992 to June 1996, 585 procedures were performed in 544 patients, including 27 free flaps in 26 patients: 17 free flaps combined with distal bypass (7 staged, 10 simultaneous) and 10 isolated free flaps. Flap donor sites included radial forearm (8), latissimus dorsi (7), rectus abdominus (9), and scapula (3). Surgical indications included extensive ischemic/neurotrophic ulcers, and nonhealing vein graft harvest incision or transmetatarsal amputation site. Mean area of tissue loss was 70 cm2, mean ulcer duration was 5 months, and 92% of patients had exposed tendon, joint, or bone. During a mean follow-up of 14 months, 2 patients died of cardiopulmonary disease and 3 flaps failed, resulting in below-knee amputation. Six flaps were revised for graft stenosis (1), venous thrombosis (1), or flap edge necrosis (4). Limb salvage rate was 70% at 24 months by life-table analysis. Functional ambulation was achieved in 21 of 24 (88%) patients, including 7 of 8 with diabetes, end-stage renal disease, and heel ulcers. CONCLUSION: In select ambulatory patients with large soft-tissue defects and exposed deep structures, functional limb salvage is obtainable in more than 80% of patients. For lesions not amenable to vascular reconstruction with conventional methods of wound coverage, free tissue transfer extends the limits of limb salvage and is a viable alternative to amputation.