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The goal of chemotherapy for metastatic breast cancer (MBC) is palliation of symptoms while minimizing treatment-related toxicities. It remains unclear whether use of granulocyte colony-stimulating factor (G-CSF) to maintain relative dose intensity of chemotherapy for MBC is associated with improved clinical outcomes. The medical records of MBC patients treated with chemotherapy in 1st–3rd-line settings between May 2010 and April 2014 were reviewed. Time to progression (TTP), progression-free survival (PFS), and overall survival (OS) were compared between patients who received G-CSF and those who did not. Antibiotic use, total clinic visits, and pre- and post-treatment Eastern Cooperative Oncology Group (ECOG) performance status were also compared between the groups. Of the 169 patients included, 55 (32.5%) received > 1 G-CSF dose and 114 (67.5%) did not receive any G-CSF. The median TTP was similar between the two groups (5.0 months (95% CI 3.4–7.1) vs. 5.2 months (95% CI 4.8–6.2) respectively; p = 0.998). The median PFS (p = 0.955; 5.0 months (95% CI 3.4–5.9) vs. 5.2 months (95% CI 4.7–6.0), respectively) and OS (14.6 (95% CI 9.0–26.6) vs. 18.5 months (95% CI 15.2–22.0) in G-CSF and non-G-CSF groups, respectively; p = 0.628) were also similar between groups. No significant between-group differences were noted in rate of decline in ECOG performance status, antibiotic use, and number of clinic visits and hospitalizations. This retrospective analysis did not find any evidence that the use of G-CSF to maintain chemotherapy dose intensity for the treatment of MBC improves TTP, PFS, and OS or results in improved ECOG performance status compared with lack of G-CSF use in patients with MBC treated in 1st to 3rd-line settings.

Patient navigation improves outcomes in various clinical contexts, but has not been evaluated in secondary fracture prevention. We retrospectively reviewed charts of patients, age 50 + from April to October, 2016 hospitalized with fragility fracture contacted by a patient navigator. Patients were identified using an electronic tool extracting data from electronic medical records which alerted the patient navigator to contact patients by phone post-discharge to schedule appointments to “High-Risk Osteoporosis Clinic” (HiROC) and Dual-energy X-ray Absorptiometry (DXA) scan. Primary outcome was transition from hospital to HiROC. We also compared completion of DXA, five osteoporosis-associated in-hospital laboratory tests (calcium, 25-hydroxy vitamin D, complete blood count, renal, and liver function), osteoporosis medication prescription and adherence, and other patient characteristics to historical controls (2014–2015) without patient navigation. Comparisons were made using Chi-square, Fisher’s Exact, two-sample t test or Wilcoxon Rank Sum test, as appropriate. The proportion of patients transitioning to HiROC with and without patient navigation was not different (53% vs. 48%, p = 0.483), but DXA scan completion was higher (90% vs. 67%, p = 0.006). No difference in medication initiation within 3 months post discharge (73% vs. 65%, p = 0.387) or adherence at 6 months (68% vs. 71%, p = 0.777) was found. Patients attending HiROC lived closer (11 vs. 43 miles, p

Purpose Capecitabine is widely used as a single agent on a 21-day cycle in the management of metastatic breast cancer (MBC). Our primary objective was to compare the standard dosing of capecitabine (Arm A: days 1–14 on 21-day cycle) to biweekly dosing (Arm B: days 1–7 and 15–21 on 28-day cycle) using retrospective data analysis. Methods 166 patients with MBC treated with single agent capecitabine at The Ohio State University from 2002 to 2014 were considered eligible. Median time to treatment failure (TTF) and overall survival (OS) were estimated using Kaplan-Meier (KM) methods. KM curves were compared using log-rank tests with Holm’s correction for multiplicity. Results Patients were grouped by dose schedule into one of three arms: Arm A (21-day cycle; capecitabine given at 1000 mg/m2 orally, twice daily on days 1–14 of 21-day cycle); Arm B (28-day cycle; capecitabine given at 1000 mg/m2 orally, twice daily on days 1–7 and 15–21 of 28-day cycle); and Arm C (changeover regimen where patients started on the 21-day cycle, but changed to a 28-day cycle for tolerability). No difference was found in TTF or OS for patients with MBC between those who received capecitabine on either standard dosing (Arm A) and those on a biweekly cycle (Arm B or C). Overall, 41% of patients required dose reduction. Conclusions Our single institution experience showed that alternate dosing of capecitabine (biweekly, 28-day cycle) may be a reasonable alternative to standard 21-day cycle with similar efficacy and fewer dose reductions.

Background Older adults in the emergency department (ED) are at high risk for functional decline, unrecognized delirium, falls, and medication interactions. Holistic assessment by a multidisciplinary team in the ED decreases these adverse outcomes and decreases admissions, but there are many barriers to incorporating this type of care during the ED visit. Methods This is a hybrid type II effectiveness-implementation study using a pre-/post-cohort design (n = 380) at a tertiary care academic ED with an ED observation unit (Obs Unit). The intervention is a two-step protocol of (step 1) ED nurses screening adult patients ≥ 65 years old for geriatric needs using the Delirium Triage Screen, 4-Stage Balance Test, and the Identifying Seniors at Risk score. Patients who have geriatric needs identified by this screening but who do not meet hospital admission criteria will (step 2) be placed in the Obs Unit for multidisciplinary geriatric assessment by the hospital’s geriatric consultation team, physical therapists, occupational therapists, pharmacists, and/or case managers. Not all patients may require all elements of the multidisciplinary geriatric assessment. The Consolidated Framework for Implementation Research: Care Transitions Framework was used to identify barriers to implementation. Lean Six Sigma processes will be used to overcome these identified barriers with the goal of achieving geriatric screening rates of > 80%. Implementation success and associated factors will be reported. For the effectiveness aim, pre-/post-cohorts of adults ≥ 65 years old cared for in the Obs Unit will be followed for 90 days post-ED visit (n = 150 pre and 230 post). The primary outcome is the prevention of functional decline. Secondary outcomes include health-related quality of life, new geriatric syndromes identified, new services provided, and Obs Unit metrics such as length of stay and admission rates. Discussion A protocol for implementing integrated multidisciplinary geriatric assessment into the ED setting has the potential to improve patient functional status by identifying and addressing geriatric issues and needs prior to discharge from the ED. Using validated frameworks and implementation strategies will increase our understanding of how to improve the quality of ED care for older adults in the acute care setting. Trial registration ClinicalTrials.gov Identifier, NCT04068311, registered 28 August 2019

There are care gaps in the evaluation and treatment of osteoporosis after a fragility fracture. The Joint Commission is considering adoption of core measures. We compared compliance between two secondary fracture prevention programs in our institution. Incorporating strengths of both may provide the best outcomes for secondary fracture prevention.There are significant care gaps in the evaluation and treatment of osteoporosis after occurrence of fragility fracture. The Joint Commission is considering adoption of a core measure set on osteoporosis-associated fractures, including laboratory assessment, bone density testing, and osteoporosis pharmacologic therapy. We compared compliance to these proposed measures between two secondary fracture prevention programs in patients hospitalized for acute fracture in an open medical system.We conducted a retrospective, single center medical records review of a nurse practitioner-led Fracture Liaison Service (FLS), a physician-led Fracture Prevention Program (FPP), and a historical time without any secondary fracture prevention program (Usual Care) for baseline care. Primary outcomes were the completion of five laboratory tests (calcium, 25-hydroxy vitamin D, renal function, liver function, and complete blood count), order placement and completion of dual x-ray absorptiometry (DXA) scan within 3 months, prescription of osteoporosis medication within 3 months, and medication adherence at 6 months after hospital discharge.Completion of all five laboratory tests was higher in FPP versus FLS (84.7 vs. 36.9%, p 0.001). DXA scan completion was higher in FPP than FLS but not statistically significant (66.7 vs. 54.9%, p = 0.11). Medication prescription at 3 months and adherence at 6 months were significantly higher in FPP versus FLS (65.3 vs. 24.0%, p 0.001 and 70.8 vs. 27.7%, p 0.001, respectively).Incorporating strengths of both FLS (care coordination) and FPP (physician direction) may provide the best outcomes for secondary fracture prevention by ensuring laboratory and DXA testing and initiating osteoporosis medication.

We discuss how the Arab Spring is a reflection of the resiliency of the human rights regime. In order to accomplish this, we explore the extent to which the Arab Spring represents norm diffusion among Middle East and North Africa (MENA) states. Specifically, we examine the cases of Tunisia, Egypt, and Bahrain and consider how economic and demographic changes created space for human rights discourse in these countries. We find that, in the case of MENA states, the Arab Spring represents significant pressure from below. Access to new forms of social media allowed civil society to organize, publicize, and protest relatively efficiently. Social media expanded the potential role of individuals and created newly empowered latent human rights activists who emerged as leaders of the norm diffusion process. The resulting diffusion of human rights norms in the Arab region represents one of the most significant expansions of the human rights regime since the regime’s inception.

The tumour stroma is believed to contribute to some of the most malignant characteristics of epithelial tumours. However, signalling between stromal and tumour cells is complex and remains poorly understood. Here we show that the genetic inactivation of Pten in stromal fibroblasts of mouse mammary glands accelerated the initiation, progression and malignant transformation of mammary epithelial tumours. This was associated with the massive remodelling of the extracellular matrix (ECM), innate immune cell infiltration and increased angiogenesis. Loss of Pten in stromal fibroblasts led to increased expression, phosphorylation (T72) and recruitment of Ets2 to target promoters known to be involved in these processes. Remarkably, Ets2 inactivation in Pten stroma-deleted tumours ameliorated disruption of the tumour microenvironment and was sufficient to decrease tumour growth and progression. Global gene expression profiling of mammary stromal cells identified a Pten-specific signature that was highly represented in the tumour stroma of patients with breast cancer. These findings identify the Pten-Ets2 axis as a critical stroma-specific signalling pathway that suppresses mammary epithelial tumours.

An increasing trend in the use of contralateral prophylactic mastectomy (CPM) for the treatment of unilateral breast cancer has been observed nationally. The purpose of this study was to confirm this trend and to identify differences between the groups that chose unilateral mastectomy alone or with CPM. A prospectively maintained breast cancer database was retrospectively reviewed. Age, histologic grade, stage, education, family history, tumor receptor status, and use of immediate reconstruction were evaluated. Statistical analysis was performed by Fisher’s exact test, χ2 test, and Student’s t-test. Between 1998 and 2007, a total of 1639 women who selected UM and 201 who had UM and CPM for unilateral breast cancer were identified. An increasing trend in CPM was observed (6.5% in 1999 vs. 16.1% in 2007). The CPM group was significantly younger (mean age 47.8 vs. 55.1 years, P

We argue that the post-9/11 environment has amounted to a substantive change in the longstanding United States relationship with the international human rights regime. We identify three distinct phases of that relationship, noting that in the most recent phase, since 9/11, the US has moved from passive support of the international human rights regime to a direct attack of that regime. Realist and liberal regime theories suggest that the human rights regime is relatively weak, and is unlikely to withstand such an attack. We find that the regime has not only continued to persist, but has flourished even as US support has faltered. The human rights regime is surprisingly strong. We argue it is the ideological nature of the regime that explains its resilience, which suggests that constructivist theory is necessary to fully understand the human rights regime.

Ipsilateral deviation of the uterus (IDU) has been suggested to be specific for torsion.To investigate the sensitivity and specificity of IDU in diagnosing torsion.We retrospectively reviewed the pelvic US examinations in girls performed at Nationwide Children's Hospital in 2007 and compared the uterine position in girls with a normal US scan (group 1) or with adnexal masses (group 2) with the uterine position in girls with torsion (group 3).Uterine deviation was found in 7 of 297 girls (2%) in group 1 and in 6 of 47 (13%) in group 2, and was attributed to stool in the colon splaying the adnexa and uterus. In group 3, 18 of 44 girls (41%) had moderate or marked uterine deviation and none was associated with stool displacing the uterus. Uterine deviation was more common and severe in girls in group 3 than in girls in group 1 (P0.001) and group 2 (P=0.010). The sensitivity and specificity of IDU for torsion were 41% and 98%, respectively.IDU is more common in adnexal torsion than in other causes of adnexal masses. With supporting clinical and imaging findings, IDU appears to be a specific marker for torsion.

An important principle of the func- tional organization of plant cells is the targeting of proteins to specific subcellular locations. The physical location of proteins within the apoplasm/ rhizosphere at the root-soil interface positions them to play a strategic role in plant response to biotic and abiotic stress. We previously demon

We have taken a systematic genetic approach to study the potential role of glutathione metabolism in aluminum (Al) toxicity and resistance, using disruption mutants available in Saccharomyces cerevisiae. Yeast disruption mutants defective in phospholipid hydroperoxide glutathione peroxidases (PHGPX; phgpx1 Delta, phgpx2 Delta, and phgpx3Delta), were tested for their sensitivity to Al. The triple mutant, phgpx1 Delta/2Delta/3Delta, was more sensitive to Al (55% reduction in growth at 300 microM Al) than any single phgpx mutant, indicating that the PHGPX genes may collectively contribute to Al resistance. The hypersensitivity of phgpx3Delta to Al was overcome by complementation with PHGPX3, and all PHGPX genes showed increased expression in response to Al in the wild-type strain (YPH250), with maximum induction of approximately 2.5-fold for PHGPX3. Both phgpx3Delta and phgpx1Delta/2Delta/3Delta mutants were sensitive to oxidative stress (exposure to H(2)O(2) or diamide). Lipid peroxidation was also increased in the phgpx1Delta/2Delta/3Delta mutant compared to the parental strain. Disruption mutants defective in genes for glutathione S-transferases (GSTs) (gtt1Delta and gtt2Delta), glutathione biosynthesis (gsh1Delta and gsh2Delta), glutathione reductase (glr1Delta) and a glutathione transporter (opt1Delta) did not show hypersensitivity to Al relative to the parental strain BY4741. Interestingly, a strain deleted for URE2, a gene which encodes a prion precursor with homology to GSTs, also showed hypersensitivity to Al. The hypersensitivity of the ure2Delta mutant could be overcome by complementation with URE2. Expression of URE2 in the parental strain increased approximately 2-fold in response to exposure to 100 microM Al. Intracellular oxidation levels in the ure2Delta mutant showed a 2-fold (non-stressed) and 3-fold (when exposed-to 2 mM H(2)O(2)) increase compared to BY4741; however, the ure2Delta mutant showed no change in lipid peroxidation compared to the control. The phgpx1Delta/2Delta/3Delta and ure2Delta mutants both showed increased accumulation of Al. These findings suggest the involvement of PHGPX genes and a novel role of URE2 in Al toxicity/resistance in S. cerevisiae.