Emerging treatment options for short bowel syndrome: potential role of teduglutide

INTRODUCTION: Current medical management of short bowel syndrome (SBS) involves the use of lifelong parenteral nutrition (PN). Glucagon-like peptide-2 (GLP-2), an important intestinotrophic growth factor has been shown to increase intestinal absorption in SBS through augmentation of post-resection intestinal adaptation. This may lead to the reduction of PN dependence in patients with SBS. AREAS COVERED IN REVIEW: Advancing research of GLP-2 physiology has spurred the growing understanding of the diverse effects of GLP-2. The development of the degradation resistant GLP-2 analog, teduglutide (Gattex(TM), NPS Pharmaceuticals, Bedminster, NJ), has allowed its exploration as a therapeutic agent in a variety of clinical settings. Recent multicenter, placebo-controlled studies of GLP-2 in SBS patients demonstrate meaningful reductions in PN requirements with good safety profiles. The reparative and immunomodulatory effects of teduglutide may also be beneficial in patients with inflammatory bowel disease (IBD). Safety concerns about possible carcinogenic properties during long-term use require ongoing evaluation. SUMMARY: GLP-2 appears to offer a novel adjuvant treatment modality for SBS. Promise for its use in other clinical settings like IBD has been shown in small pilot studies

Healthcare choice: Discourses, perceptions, experiences and practices

Policy discourse shaped by neoliberal ideology, with its emphasis on marketisation and competition, has highlighted the importance of choice in the context of healthcare and health systems globally. Yet, evidence about how so-called consumers perceive and experience healthcare choice is in short supply and limited to specific healthcare systems, primarily in the Global North. This special issue aims to explore how choice is perceived and utilised in the context of different systems of healthcare throughout the world, where choice, at least in policy and organisational terms, has been embedded for some time. The articles are divided into those emphasising: embodiment and the meaning of choice; social processes associated with choice; the uncertainties, risks and trust involved in making choices; and issues of access and inequality associated with enacting choice. These sociological studies reveal complexities not always captured in policy discourse and suggest that the commodification of healthcare is particularly problematic

Perceptions of 24/7 In‐house Attending Coverage on Fellow Education and Autonomy in a Pediatric Cardiothoracic Intensive Care Unit

BackgroundThe 24/7 in‐house attending coverage is emerging as the standard of care in intensive care units. Implementation costs, workforce feasibility, and patient outcomes resulting from changes in physician staffing are widely debated topics. Understanding the impact of staffing models on the learning environment for medical trainees and faculty is equally warranted, particularly with respect to trainee education and autonomy.ObjectiveThis study aims to elicit the perceptions of pediatric cardiology fellows and attendings toward 24/7 in‐house attending coverage and its effect on fellow education and autonomy.MethodsWe surveyed pediatric cardiology fellows and attendings practicing in the pediatric cardiothoracic intensive care unit (PCTU) of a large, university‐affiliated medical center, using structured Likert response items and open‐ended questions, prior to and following the transition to 24/7 in‐house attending coverage.ResultsAll (100%) trainees and faculty completed all surveys. Both prior to and following transition to 24/7 in‐house attending coverage, all fellows, and the majority of attendings agreed that the overnight call experience benefited fellow education. At baseline, trainees identified limited circumstances in which on‐site attending coverage would be critical. Preimplementation concerns that 24/7 in‐house attending coverage would negatively affect the education of fellows were not reflected following actual implementation of the new staffing policy. However, based upon open‐ended questions, fellow autonomy was affected by the new paradigm, with fellows and attendings reporting decreased “appropriateness” of autonomy after implementation.ConclusionsOur prospective study, showing initial concerns about limiting the learning environment in transitioning to 24/7 in‐house attending coverage did not result in diminished perceptions of the educational experience for our fellows but revealed an expected decrease in fellow autonomy. The study indirectly facilitated open discussions about methods to preserve fellow education and warranted autonomy in our PCTU; however, continued efforts are needed to achieve the optimal balance between supervised training and the transition to autonomous practice.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/111990/1/chd12261.pd

Designing sensor sets for capturing energy events in buildings

Belgium Herbarium image of Meise Botanic Garden

Dynamic Time-Warping Correction for Shifts in Ultrahigh Resolving Power Ion Mobility Spectrometry and Structures for Lossless Ion Manipulations

Detection of arrival time shifts between ion mobility spectrometry (IMS) separations can limit achievable resolving power (Rp), particularly when multiple separations are summed or averaged, as commonly practiced in IMS. Such variations can be apparent in higher Rp measurements and are particularly evident in long path length traveling wave structures for lossless ion manipulations (SLIM) IMS due to their typically much longer separation times. Here, we explore data processing approaches employing single value alignment (SVA) and nonlinear dynamic time warping (DTW) to correct for variations between IMS separations, such as due to pressure fluctuations, to enable more effective spectrum summation for improving Rp and detection of low-intensity species. For multipass SLIM IMS separations, where narrow mobility range measurements have arrival times that can extend to several seconds, the SVA approach effectively corrected for such variations and significantly improved Rp for summed separations. However, SVA was much less effective for broad mobility range separations, such as obtained with multilevel SLIM IMS. Changes in ions’ arrival times were observed to be correlated with small pressure changes, with approximately 0.6% relative arrival time shifts being common, sufficient to result in a loss of Rp for summed separations. Comparison of the approaches showed that DTW alignment performed similarly to SVA when used over a narrow mobility range but was significantly better (providing narrower peaks and higher signal intensities) for wide mobility range data. We found that the DTW approach increased Rp by as much as 115% for measurements in which 50 IMS separations over 2 s were summed. We conclude that DTW is superior to SVA for ultra-high-resolution broad mobility range SLIM IMS separations and leads to a large improvement in effective Rp, correcting for ion arrival time shifts regardless of the cause, as well as improving the detectability of low-abundance species. Our tool is publicly available for use with universal ion mobility format (.UIMF) and text (.txt) files

Therapeutic targeting of integrin αvβ6 in breast cancer

BACKGROUND: Integrin ?v?6 promotes migration, invasion, and survival of cancer cells; however, the relevance and role of ?v?6 has yet to be elucidated in breast cancer.METHODS: Protein expression of integrin subunit beta6 (?6) was measured in breast cancers by immunohistochemistry (n &gt; 2000) and ITGB6 mRNA expression measured in the Molecular Taxonomy of Breast Cancer International Consortium dataset. Overall survival was assessed using Kaplan Meier curves, and bioinformatics statistical analyses were performed (Cox proportional hazards model, Wald test, and Chi-square test of association). Using antibody (264RAD) blockade and siRNA knockdown of ?6 in breast cell lines, the role of ?v?6 in Human Epidermal Growth Factor Receptor 2 (HER2) biology (expression, proliferation, invasion, growth in vivo) was assessed by flow cytometry, MTT, Transwell invasion, proximity ligation assay, and xenografts (n ? 3), respectively. A student's t-test was used for two variables; three-plus variables used one-way analysis of variance with Bonferroni's Multiple Comparison Test. Xenograft growth was analyzed using linear mixed model analysis, followed by Wald testing and survival, analyzed using the Log-Rank test. All statistical tests were two sided.RESULTS: High expression of either the mRNA or protein for the integrin subunit ?6 was associated with very poor survival (HR = 1.60, 95% CI = 1.19 to 2.15, P = .002) and increased metastases to distant sites. Co-expression of ?6 and HER2 was associated with worse prognosis (HR = 1.97, 95% CI = 1.16 to 3.35, P = .01). Monotherapy with 264RAD or trastuzumab slowed growth of MCF-7/HER2-18 and BT-474 xenografts similarly (P &lt; .001), but combining 264RAD with trastuzumab effectively stopped tumor growth, even in trastuzumab-resistant MCF-7/HER2-18 xenografts.CONCLUSIONS: Targeting ?v?6 with 264RAD alone or in combination with trastuzumab may provide a novel therapy for treating high-risk and trastuzumab-resistant breast cancer patients.<br/

TeV physics and the Planck scale

Supersymmetry is one of the best motivated possibilities for new physics at the TeV scale. However, both concrete string constructions and phenomenological considerations suggest the possibility that the physics at the TeV scale could be more complicated than the Minimal Supersymmetric Standard Model (MSSM), e.g., due to extended gauge symmetries, new vector-like supermultiplets with non-standard SU(2)xU(1) assignments, and extended Higgs sectors. We briefly comment on some of these possibilities, and discuss in more detail the class of extensions of the MSSM involving an additional standard model singlet field. The latter provides a solution to the $\mu$ problem, and allows significant modifications of the MSSM in the Higgs and neutralino sectors, with important consequences for collider physics, cold dark matter, and electroweak baryogenesis.Comment: 17 pages, 5 figures. To appear in New Journal of Physic

Heterogeneous Agglomeration

Many prior treatments of agglomeration explicitly or implicitly assume that all industries agglomerate for the same reasons. This paper uses U.K. establishment-level coagglomeration data to document substantial heterogeneity across industries in the microfoundations of agglomeration economies. It finds robust evidence of organizational and adaptive agglomeration forces as discussed by Chinitz (1961), Vernon (1960), and Jacobs (1969). These forces interact with the traditional Marshallian (1890) factors of input sharing, labor pooling, and knowledge spillovers, establishing a previously unrecognized complementarity between the approaches of Marshall and Jacobs, as well as others, to the analysis of agglomeration