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Impairment in psychosocial functioning complicates readjustment to civilian life for many combat veterans with PTSD and is related to poorer quality of life. Hope theory posits that both a sense of agency and the ability to identify pathways toward achieving a goal underlie the process of behavior change. We developed an intensive outpatient program (the HOME program) in order to help combat veterans move toward values-driven activities and improve psychosocial functioning. We hypothesized that increased hope regarding veterans’ ability to manage and recover from PTSD symptoms may facilitate improvements in functioning apart from symptom reduction. The present study examines changes in hope, psychosocial functioning, and PTSD symptoms in a sample of HOME participants (N = 33). Consistent with our hypothesis, results indicated that greater levels of hope were associated with improvements in adaptive behaviors (related to functioning) above and beyond symptom change. These preliminary findings suggest that therapeutic interventions that increase veterans’ perceptions of hope regarding recovery from PTSD may enhance psychosocial functioning. Additional research with larger samples is needed to further examine these relationships.

Pancreatic cancer statistics are dismal, with a 5-year survival of less than 10%, and more than 50% of patients presenting with metastatic disease. Metabolic reprogramming is an emerging hallmark of pancreatic adenocarcinoma. CPI-613 is a novel anticancer agent that selectively targets the altered form of mitochondrial energy metabolism in tumour cells, causing changes in mitochondrial enzyme activities and redox status that lead to apoptosis, necrosis, and autophagy of tumour cells. We aimed to establish the maximum tolerated dose of CPI-613 when used in combination with modified FOLFIRINOX chemotherapy (comprising oxaliplatin, leucovorin, irinotecan, and fluorouracil) in patients with metastatic pancreatic cancer. In this single-centre, open-label, dose-escalation phase 1 trial, we recruited adult patients (aged ≥18 years) with newly diagnosed metastatic pancreatic adenocarcinoma from the Comprehensive Cancer Center of Wake Forest Baptist Medical Center (Winston-Salem, NC, USA). Patients had good bone marrow, liver and kidney function, and good performance status (Eastern Cooperative Oncology Group [ECOG] performance status 0–1). We studied CPI-613 in combination with modified FOLFIRINOX (oxaliplatin at 65 mg/m2, leucovorin at 400 mg/m2, irinotecan at 140 mg/m2, and fluorouracil 400 mg/m2 bolus followed by 2400 mg/m2 over 46 h). We applied a two-stage dose-escalation scheme (single patient and traditional 3+3 design). In the single-patient stage, one patient was accrued per dose level. The starting dose of CPI-613 was 500 mg/m2 per day; the dose level was then escalated by doubling the previous dose if there were no adverse events worse than grade 2 within 4 weeks attributed as probably or definitely related to CPI-613. The traditional 3+3 dose-escalation stage was triggered if toxic effects attributed as probably or definitely related to CPI-613 were grade 2 or worse. The dose level for CPI-613 for the first cohort in the traditional dose-escalation stage was the same as that used in the last cohort of the single-patient dose-escalation stage. The primary objective was to establish the maximum tolerated dose of CPI-613 (as assessed by dose-limiting toxicities). This trial is registered with ClinicalTrials.gov, number NCT01835041, and is closed to recruitment. Between April 22, 2013, and Jan 8, 2016, we enrolled 20 patients. The maximum tolerated dose of CPI-613 was 500 mg/m2. The median number of treatment cycles given at the maximum tolerated dose was 11 (IQR 4–19). Median follow-up of the 18 patients treated at the maximum tolerated dose was 378 days (IQR 250–602). Two patients enrolled at a higher dose of 1000 mg/m2, and both had a dose-limiting toxicity. Two unexpected serious adverse events occurred, both for the first patient enrolled. Expected serious adverse events were: thrombocytopenia, anaemia, and lymphopenia (all for patient number 2; anaemia and lymphopenia were dose-limiting toxicities); hyperglycaemia (in patient number 7); hypokalaemia, hypoalbuminaemia, and sepsis (patient number 11); and neutropenia (patient number 20). No deaths due to adverse events were reported. For the 18 patients given the maximum tolerated dose, the most common grade 3–4 non-haematological adverse events were hyperglycaemia (ten [55%] patients), hypokalaemia (six [33%]), peripheral sensory neuropathy (five [28%]), diarrhoea (five [28%]), and abdominal pain (four [22%]). The most common grade 3–4 haematological adverse events were neutropenia (five [28%] of 18 patients), lymphopenia (five [28%]), anaemia (four [22%], and thrombocytopenia in three [17%]). Sensory neuropathy (all grade 1–3) was recorded in 17 (94%) of the 18 patients and was managed with dose de-escalation or discontinuation per standard of care. No patients died while on active treatment; 11 study participants died, with cause of death as terminal pancreatic cancer. Of the 18 patients given the maximum tolerated dose, 11 (61%) achieved an objective (complete or partial) response. A maximum tolerated dose of CPI-613 was established at 500 mg/m2 when used in combination with modified FOLFIRINOX in patients with metastatic pancreatic cancer. The findings of clinical activity will require validation in a phase 2 trial. Comprehensive Cancer Center of Wake Forest Baptist Medical Center.

College students are at particular risk for sexual assault victimization, yet research tends to focus on women as victims and men as perpetrators. The purpose of this study was to investigate gender differences in the prevalence, context, and predictors of sexual assault victimization among college students. Results showed that women were significantly more likely to have been sexually assaulted in a 2-month time period, but the context of victimization varied little by gender. Victimization was predicted by sexual orientation, time spent socializing and partying, and severe dating violence victimization for men and by year in school, time spent on the Internet, drinking and using drugs, and being a stalking and dating violence victim for women. Results are discussed in the context of routine activities theory and implications for prevention and future research.

Falls are a frequent reason geriatric patients visit the emergency department (ED). To help providers, the Geriatric Emergency Department Guidelines were created to establish a standard of care for geriatric patients in the ED. We conducted a survey of emergency providers to assess 1) their knowledge of fall epidemiology and the geriatric ED guidelines; 2) their current ED practice for geriatric fall patients; and 3) their willingness to conduct fall-prevention interventions. We conducted an anonymous survey of emergency providers including attending physicians, residents, and physician assistants at a single, urban, Level 1 trauma, tertiary referral hospital in the northeast United States. We had a response rate of 75% (102/136). The majority of providers felt that all geriatric patients should undergo screening for fall risk factors (84%, 86/102), and most (76%, 77/102) answered that all geriatric patients screened and at risk for falls should have an intervention performed. While most (80%, 82/102) answered that geriatric falls prevention was very important, providers were not willing to spend much time on screening or interventions. Less than half (44%, 45/102) were willing to spend 2-5 minutes on a fall risk assessment and prevention, while 46% (47/102) were willing to spend less than 2 minutes. Emergency providers understand the importance of geriatric fall prevention but lack knowledge of which patients to screen and are not willing to spend more than a few minutes on screening for fall interventions. Future studies must take into account provider knowledge and willingness to intervene.

Spondyloarthritis (SpA) is an inflammatory arthritis of the spine and joints associated with intestinal inflammation, in which it is hypothesized that innate immune exposure to enteroinvasive species is followed by self-/bacterial peptide presentation. However, the mechanisms underlying loss of tolerance to gut bacteria in genetically at-risk individuals are unclear. Curdlan-treated (β-1,3-glucan, dectin-1 ligand-treated) ZAP-70W163C (SKG) mice develop autoimmune arthritis and ileitis associated with Gram-negative fecal dysbiosis. Using gnotobiotic mice, we show that curdlan-treated SKG mice monoassociated with Parabacteroides goldsteinii or Lactobacillus murinus developed ileitis, arthritis, and enthesitis, while BALB/c mice were tolerant. Gnotobiotic SKG ileum upregulated Il23a and ER stress genes and lost goblet cells. Whereas bacterial DNA colocalized with neutrophils and inflammatory macrophages in SKG lamina propria, periarticular bone marrow, entheses, and spleen, in BALB/c mice, bacterial DNA colocalized with resident macrophages in lamina propria and spleen. Human psoriatic-arthritis synovial tissue also contained cell-associated perivascular bacterial DNA. Curdlan-treated SKG spleen/bone marrow macrophages transferred severe arthritis and expanded Th17 cells in naive SKG recipients, while BALB/c or germ-free SKG macrophages transferred mild arthritis and regulated Th17 cells. Thus, bacterial DNA and myeloid cells in the gut and their subsequent traffic regulate or enforce T cell pathogenicity in SpA.

: Dialectical behavior therapy (DBT) is one empirically supported treatment for individuals diagnosed with borderline personality disorder (BPD), and has demonstrated efficacy in reducing distress and behaviors that are often utilized by those with BPD to manage that distress. Treatment dropout rates of those with BPD receiving DBT are high, with serious deleterious effects. Increasing motivation for treatment, including treatment adherence, homework completion and skill use, in those with BPD is a critical factor in improving daily functioning and overall quality of life for these individuals. As described in ACT, values work in the service of increasing values-consistent behavior, or valued or committed action, may be one way to improve treatment motivation both in-session and out of session. This paper outlines the theoretical rationale for adding values components to existing DBT skills, including suggestions for where and how values work might be done in this population and potential difficulties.

In the field of optical imaging, the ability to image tumors at depth with high selectivity and specificity remains a challenge. Surface enhanced resonance Raman scattering (SERRS) nanoparticles (NPs) can be employed as image contrast agents to specifically target cells in vivo; however, this technique typically requires time-intensive point-by-point acquisition of Raman spectra. Here, we combine the use of “spatially offset Raman spectroscopy” (SORS) with that of SERRS in a technique known as “surface enhanced spatially offset resonance Raman spectroscopy” (SESORRS) to image deep-seated tumors in vivo. Additionally, by accounting for the laser spot size, we report an experimental approach for detecting both the bulk tumor, subsequent delineation of tumor margins at high speed, and the identification of a deeper secondary region of interest with fewer measurements than are typically applied. To enhance light collection efficiency, four modifications were made to a previously described custom-built SORS system. Specifically, the following parameters were increased: (i) the numerical aperture (NA) of the lens, from 0.2 to 0.34; (ii) the working distance of the probe, from 9 mm to 40 mm; (iii) the NA of the fiber, from 0.2 to 0.34; and (iv) the fiber diameter, from 100 µm to 400 µm. To calculate the sampling frequency, which refers to the number of data point spectra obtained for each image, we considered the laser spot size of the elliptical beam (6 × 4 mm). Using SERRS contrast agents, we performed in vivo SESORRS imaging on a GL261-Luc mouse model of glioblastoma at four distinct sampling frequencies: par-sampling frequency (12 data points collected), and over-frequency sampling by factors of 2 (35 data points collected), 5 (176 data points collected), and 10 (651 data points collected). In comparison to the previously reported SORS system, the modified SORS instrument showed a 300% improvement in signal-to-noise ratios (SNR). The results demonstrate the ability to acquire distinct Raman spectra from deep-seated glioblastomas in mice through the skull using a low power density (6.5 mW/mm 2 ) and 30-times shorter integration times than a previous report (0.5 s versus 15 s). The ability to map the whole head of the mouse and determine a specific region of interest using as few as 12 spectra (6 s total acquisition time) is achieved. Subsequent use of a higher sampling frequency demonstrates it is possible to delineate the tumor margins in the region of interest with greater certainty. In addition, SESORRS images indicate the emergence of a secondary tumor region deeper within the brain in agreement with MRI and H&E staining. In comparison to traditional Raman imaging approaches, this approach enables improvements in the detection of deep-seated tumors in vivo through depths of several millimeters due to improvements in SNR, spectral resolution, and depth acquisition. This approach offers an opportunity to navigate larger areas of tissues in shorter time frames than previously reported, identify regions of interest, and then image the same area with greater resolution using a higher sampling frequency. Moreover, using a SESORRS approach, we demonstrate that it is possible to detect secondary, deeper-seated lesions through the intact skull.