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Introduction Current standard of care (SOC) for treatment of HCV Genotype 1 (G1) naive patients comprises of pegylated interferon (P) plus ribavirin (R) for 48 weeks resulting in a sustained viral response (SVR) of 42 to 46% in treated patients. Telaprevir (TVR) is a novel selective inhibitor of the HCV NS3-4A protease. We report here results from phase II program. Method PROVE 1 (n=263) and PROVE 2 (n=334) were randomised controlled phase IIb comparisons of 12 weeks TVR plus PR up to 48 weeks vs PR alone in G1 treatment-naïve patients. In the same population, the C208 study (n=161) compared TVR dosed every 8 h or every 12 h in combination with P2a or P2b with a response guided therapy design. In treatment experienced patients, the PROVE 3 trial (n=453) compared different TVR-based regimens to PR. Results Higher SVRs compared to SOC in treatment-naive subjects were observed in the TVR groups (61–69%) in the PROVE 1 and 2 studies as well as the C208 study (81–85%). In PROVE 3, 51% (vs. 14% in control) of previous non-responders achieved SVR. The most common AEs through week 48 included; pruritus, rash, anemia, fatigue, weakness and headaches. Overall discontinuation of all drugs due to rash was observed in 4–7% of the subjects. Conclusion TVR-based triple therapy significantly improves SVR rates in comparison to SOC in G1 HCV infected patients. It offers the potential to reduce treatment duration by half in the majority of treatment-naive patients. Phase III studies of TVR-based regimen are currently underway. [ABSTRACT FROM PUBLISHER]

Tobacco smoking is highly prevalent in persons with psychosis and is the leading cause of preventable mortality in this population. Less is known about tobacco smoking in persons with first episode psychosis (FEP) and there have been no estimates about the prevalence of nicotine vaping in FEP. This study reports rates of tobacco smoking and nicotine vaping in young people with FEP enrolled in Coordinated Specialty Care programs in Pennsylvania and Maryland. Using data collected from 2021 to 2023, we examined lifetime and recent smoking and vaping and compared smokers and vapers to nonusers on symptoms, functioning, and substance use. The sample included 445 participants aged 13-35 with recent psychosis onset. Assessments were collected by program staff. Overall, 28 % of participants engaged in either smoking or vaping within 30 days of the admission assessment. Smokers and vapers were disproportionately male, cannabis users, and had lower negative symptom severity than non-smokers. Vapers had higher role and social functioning. Both smoking and vaping were related to a longer time from psychosis onset to program enrollment. We compare these findings to previous studies and suggest steps for addressing smoking and vaping in this vulnerable population., Competing Interests: Declaration of competing interest, (Copyright © 2024 Elsevier B.V. All rights reserved.)

Background: Since their inception, Integrated Vascular Surgery Residency (IVSR) programs have expanded widely and attracted highly competitive medical students by offering a more focused approach to learning both open surgical and endovascular techniques. However, despite substantial modifications to the training paradigm, a shortage of vascular surgeons is still projected through 2050. We aimed to gather and analyze fourth-year medical students' knowledge and perceptions of vascular surgery (VS) to further inform strategies for recruiting future vascular surgeons., Methods: We sent anonymous electronic questionnaires to fourth-year medical students at 7 allopathic and 3 osteopathic medical schools, with questions detailing demographics, specialty preferences, and exposure to and perceptions of VS. Descriptive statistics were obtained, and responses were compared between students applying to surgical specialties (SS) and nonsurgical specialties (NSS)., Results: Two hundred eleven of 1,764 (12%) participants responded (56% female). 56% reported VS exposure, most commonly during the third year. 64 (30%) planned to apply to SS. 57% of respondents reported knowledge of the management of vascular disease, and 56% understood procedures performed by vascular surgeons. Ranking the importance of factors in choosing specialties, SS selected "experiences gained during medical school rotations" (P < 0.05), "types and/or variety of treatment modalities used in this field" (P < 0.001), and "interest in the pathology or disease processes treated" (P < 0.05) as highest priorities. NSS preferred "lifestyle (work-life balance) as an attending" (P < 0.001). Only 7% of all respondents believed vascular surgeons have a good work-life balance, with a larger percentage of SS (P < 0.001) agreeing. Stratified by gender, female students rated "limited ability of childbirth during residency and/or postponement of family plans" (P < 0.05), "gender-related concerns, such as discrimination at work or unfair career possibilities" (P < 0.001), and "fear of unfair competition" (P < 0.05) as potential negative aspects of VS careers. 55% of respondents believed the IVSR makes VS more appealing., Conclusions: Medical students perceive poor quality of life and work-life balance as deterring factors to a career in VS. Opportunities exist to educate students on the pathologies treated, procedures performed, and attainable quality of life available in our field. We should also continue to develop recruitment strategies to stimulate student interest and increase early exposure in VS., (Copyright © 2023 Elsevier Inc. All rights reserved.)

Black smokers demonstrate higher nicotine dependence and experience higher rates of smoking-related diseases and mortality relative to European American/White smokers. A potential factor relevant to race-specific smoking health disparities may be smoking motives (i.e., motivational basis of smoking). Yet, little research has been conducted to understand psychological factors that may be associated with specific smoking motives among Black smokers. To address this gap in the literature, the current study explored the association between anxiety sensitivity and smoking motives within a subset sample of Black smokers who were interested in participating in a smoking cessation trial (N = 105; 70.5 % male; M age  = 44.8 years, SD = 11.6 years). Hierarchical regression analyses indicated anxiety sensitivity was associated with smoking motives related to habit (β = 0.39, p <.001), negative affect reduction (β = 0.32, p <.001), stimulation (β = 0.31, p <.001), and sensorimotor manipulation (β = 0.26, p =.008). Limited support was found for the effect of motives on past quit attempt engagement. These results may broaden understanding of the psychological mechanisms related to smoking motivation among Black smokers and may inform future intervention efforts to reduce smoking motivation among this health disparities population., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2022 Elsevier Ltd. All rights reserved.)

Background: A better understanding of risk-factors associated with state-like food cravings may be one clinically relevant component in an effort to better understand obesity. Existing work has shown anxiety sensitivity (AS) to be a significant risk factor for increased cravings across a variety of health behaviors (e.g., smoking, alcohol use). Yet, no work has examined the relationship between AS and state-like food cravings. Therefore, the current study sought to examine the association between AS and a variety of state-like food cravings, including: (1) an intense desire to eat, (2) anticipation of relief from negative states and feelings/improvement in mood that may result from eating, (3) obsessive preoccupation with food or lack of control over eating, and (4) craving as a physiological state., Methods: Participants included 161 (M age  = 31.58, SD = 10.71; 60.9 % female) individuals seeking treatment for weight-related behaviors., Results: Results indicated that elevated AS was associated with reinforcement-based and physiological food cravings., Conclusion: Our findings indicate that there may be clinical utility in screening for AS among individuals seeking treatment for weight-related behaviors in efforts to better understand specific types of food craving., Competing Interests: Declaration of competing interest None., (Copyright © 2022 Elsevier Ltd. All rights reserved.)

Despite the promise of past research on anxiety sensitivity (AS) and posttraumatic stress, extant work is limited, given (1) most studies consist of non-Hispanic White and middle-aged samples, (2) few have demonstrated incremental validity to general emotional traits and social determinants of health, and (3) limited work has characterized how AS relates to specific Posttraumatic Stress Disorder (PTSD) symptom clusters among those with (probable) PTSD. The current study evaluated the role of AS in relation to PTSD symptom clusters among a racially/ethnically diverse sample of young adults with probable PTSD. Participants included young adults who met the clinical cut-off for probable PTSD per the Posttraumatic Diagnostic Scale. Results indicated that AS was significantly related to overall posttraumatic stress symptom severity; the effect was evident after adjusting for a range of covariates including neuroticism and subjective social status. AS also was incrementally associated with arousal and hyperreactivity, changes in mood and cognition, and intrusion PTSD symptom clusters. In contrast to expectation, no effect for AS was evident for the avoidance PTSD symptom cluster. The current data uniquely add to the existing AS PTSD literature by showcasing distinct symptom cluster patterns among a racially/ethnically diverse sample of young adults with probable PTSD.

Background: Firefighters are faced with numerous work-related demands and stressors, including exposure to potentially traumatic events, and are thus at an increased risk for poor mental health outcomes. To better understand the mental health of trauma-exposed firefighters, the current study sought to examine the association of fatigue sensitivity with posttraumatic stress disorder (PTSD), anxiety, and depressive symptom severity in a cross-sectional study design., Methods: Participants included 107 ( M age = 40.8 years; SD age = 8.95; age range: 21-67 years; 95.0% male) trauma-exposed firefighters., Results: Findings from the current study indicated that fatigue sensitivity was a statistically significant clinical correlate of PTSD, anxiety, and depressive symptom severity. The statistically significant incremental effects were small to medium across the mental health variables, but evident after accounting for years in the fire service, sleep quality, and trauma load., Conclusions: The present data provide initial empirical evidence for the role of fatigue sensitivity in terms of a broad range of mental health indices among trauma-exposed firefighters., Competing Interests: Disclosure Statement The authors report no conflict of interest.

Approximately two-thirds of Operations Enduring Freedom, Iraqi Freedom, and New Veterans reported knowing someone who was killed or seriously injured, lost someone in their immediate unit, or personally saw dead or seriously injured Americans (Hoge et al., 2004; Thomas et al., 2010; Toblin et al., 2012). Thus, it is not surprising that prevalence of Persistent Complex Bereavement Disorder (PCBD) is high in these groups. Importantly, PCBD impact appears to be independent of both Post-Traumatic Stress Disorder (PTSD) and Major Depressive Disorder (Bonnano, 2007), 2 disorders that are also highly prevalent in these groups, thus tailored treatments for grief are indicated. The Department of Veterans Affairs suggests Cognitive Therapy for Grief as a first line psychotherapy, however treatments relatively more focused on behavior change and exposure to grief cues also may be useful for this population. To address this question, the present study used a randomized controlled trial to compare a 7-session program of Behavioral Activation and Therapeutic Exposure for Grief vs. Cognitive Therapy for Grief among 155 OIF/OEF/OND veterans. Both treatments produced significant treatment gains over baseline, and these improvements were maintained over 6-month followup; however no differences were observed between groups. Given equal efficacy, implications for matching treatment to patient characteristics are discussed.

The present study examined the factor structure, invariance properties, reliability, and validity of the Anxiety Sensitivity Index-3 (ASI-3, Taylor et al., 2007). Participants were recruited from a large, ethnically diverse southwestern university (n = 3651; 77.8% female; M age  = 22.06 years; 28% non-Hispanic White). Findings supported a bifactor structure for the ASI-3, which demonstrated measurement invariance across sex, race/ethnicity, age, and sexual minority status. Furthermore, the ASI-3 demonstrated strong reliability and validity, with the anxiety sensitivity general and specific factors (physical, cognitive, and social concerns) evidencing unique patterns of relations with symptoms of depression, suicidality, anxious arousal, and social anxiety. Clinically, these findings generally support the validity of the ASI-3 in measuring anxiety sensitivity across sex, age, race/ethnicity, and sexual minority status. Future work is needed to better understand the role anxiety sensitivity plays within specific demographic subgroups, particularly African-Americans, Asian Americans, and sexual minorities., (Copyright © 2018. Published by Elsevier B.V.)

It is widely recognized that abdominal pain and discomfort are common problems in the United States and are often associated with negative quality of life. The prevalence of anxiety/depression elevations and disorders among persons with gastrointestinal disturbances (GI) is estimated to be at least two to three times the rate in the general population. Visceral sensitivity reflects anxiety about GI sensations and its accompanying contexts and often leads to worsening of sensations (e.g. bloating, upset stomach, diarrhea). Among individuals with GI symptoms, visceral sensitivity may be associated with interpreting common sensations as catastrophic which may be related to greater difficulties with emotion dysregulation (e.g. severe anxiety and depression). The current study evaluated the indirect association of visceral sensitivity via emotion dysregulation in relation to depression, anxious arousal, and social anxiety symptoms among 344 young adults with a current history of GI symptoms and problems. Results indicated an indirect effect of visceral sensitivity via emotion dysregulation. These findings provide novel empirical support for the association of visceral sensitivity with emotional distress symptoms among young adults with GI symptoms. Based on the results, targeting emotion dysregulation may be a promising health promotion tactic among young adults with GI symptoms and disorders.

Tropical peatlands cover an estimated 440,000 km2 (~10% of global peatland area) and are significant in the global carbon cycle by storing about 40-90 Gt C in peat. Over the past several decades, tropical peatlands have experienced high rates of deforestation and conversion, which is often associated with lowering the water table and peat burning, releasing large amounts of carbon stored in peat to the atmosphere. We present the first model of long-term carbon accumulation in tropical peatlands by modifying the Holocene Peat Model (HPM), which has been successfully applied to northern temperate peatlands. Tropical HPM (HPMTrop) is a one-dimensional, nonlinear, dynamic model with a monthly time step that simulates peat mass remaining in annual peat cohorts over millennia as a balance between monthly vegetation inputs (litter) and monthly decomposition. Key model parameters were based on published data on vegetation characteristics, including net primary production partitioned into leaves, wood, and roots; and initial litter decomposition rates. HPMTrop outputs are generally consistent with field observations from Indonesia. Simulated long-term carbon accumulation rates for 11,000-year-old inland, and 5000-year-old coastal peatlands were about 0.3 and 0.59 Mg C ha(-1) yr(-1), and the resulting peat carbon stocks at the end of the 11,000-year and 5000-year simulations were 3300 and 2900 Mg C ha(-1), respectively. The simulated carbon loss caused by coastal peat swamp forest conversion into oil palm plantation with periodic burning was 1400 Mg C ha(-1) over 100 years, which is equivalent to ~2900 years of C accumulation in a hectare of coastal peatlands., (© 2014 John Wiley & Sons Ltd.)

In the embryo of the leech Hirudo medicinalis, afferent projections of peripheral sensory neurons travel along common nerve tracts to the CNS, where they defasciculate, branch, and arborize into separate, modality-specific synaptic laminae. Previous studies have shown that this process requires, at least in part, the constitutive and then modality-specific glycosylations of tractin, a leech L1 homologue. We report here on the dynamics of growth of these projections as obtained by examining the morphology of single growing dye-filled sensory afferents as a function of time. Using 2-photon laser-scanning microscopy of the intact developing embryo, we obtained images of individual sensory projections at 3 to 30 min intervals, over several hours of growth, and at different stages of development. The time-lapse series of images revealed a highly dynamic and maturation-state-dependent pattern of growth. Upon entering the CNS, the growth cone-tipped primary axon sprouted numerous long filopodial processes, many of which appeared to undergo repeated cycles of extension and retraction. The growth cone was transformed into a sensory arbor through the formation of secondary branches that extended within the ganglionic neuropil along the anterior-posterior axis of the CNS. Numerous tertiary and quaternary processes grew from these branches and also displayed cycles of extension and retraction. The motility of these higher-order branches changed with age, with younger afferents displaying higher densities and greater motility than older, more mature sensory arbors. Finally, coincident with a reduction in higher order projections was the appearance of concavolar structures on the secondary processes. Rows of these indentations suggest the formation of presynaptic en-passant specializations accompanying the developmental onset of synapse formation., (Copyright 2003 Wiley Periodicals, Inc. J Neurobiol 56: 41-53, 2003)