Lack of Evidence for Hand Dominance In the NonHuman Primate: Difficulty for the Theory of Evolution

Most scientists believe individual nonhuman primates can exhibit hand preference in certain manual tasks, but that there is no population-based hand dominance in prosimians, monkeys or apes like there is in the human. This paper critiques the studies attempting to find hand dominance in nonhuman primates. It also critiques a recent study seeking evidence for brain asymmetry related to hand preference in squirrel monkeys. The investigators felt their data showed that the motor cortex hemisphere contralateral to the preferred hand of squirrel monkeys had a greater number of microstimulation sites that caused forelimb muscle contractions than did the ipsilateral hemisphere. Their conclusion may have been based on faulty reasoning. Any evidence that nonhuman primates have a system homologous to that of human hand dominance (or any correlated brain asymmetry) is very weak indeed. In fact, evidence from these studies of nonhuman primates would support separate ancestries of the different types of nonhuman primates and of humans; although the evidence has not been interpreted in that manner by those who have undertaken the studies

Field testing of railroad flatcar bridges

In a research project conducted by the Bridge Engineering Center at Iowa State University (ISU), the behavior of low-volume bridges composed of two railroad flatcars (RRFCs) was investigated in two previous research projects at ISU. The results of these projects verified that bridges composed of three RRFCs are efficient and economical alternatives for low-volume road bridges. To verify the adequacy of bridges composed of two RRFCs, two bridges were tested: one in Buchanan County, Iowa, and one in Delaware County, Iowa. The Buchanan County Bridge 2 (BCB2), the second Buchanan County RRFC bridge to be tested by ISU, is composed of two 56-ft V-deck RRFCs and spans 54 ft - 0 in. The RRFCs are simply-supported with concrete abutments. A reinforced concrete beam acts as the longitudinal flatcar connection (LFC) and distributes live loads between the RRFCs. The BCB2 has a gravel driving surface and a guardrail system. The Delaware County Bridge (DCB) spans 66 ft - 4 in. and is composed of two 89-ft RRFCs which were each symmetrically cut to 67 ft - 6 in. The RRFCs are supported at their bolsters by a built-up cap beam which is supported by HP piles. The LFC consists of a steel plate welded to the adjacent RRFCs along the length of the connection. The DCB also has a gravel driving surface and a guardrail system. Through the load tests, it was found that bridges designed like the BCB2 have total stresses below the allowable stress of the steel and deflections below the AASHTO bridge design specification limits. In bridges designed like the DCB, the thickness of the gravel driving surface must be limited for the total stresses and deflections to be below the allowable stress of the steel and the AASHTO bridge design specification limits. To assist bridge inspectors, live load distribution factors were developed for use with the AASHTO rating method. Based on the results of this research, it has been determined that with the proper driving surface, bridges composed of two RRFCs are an effective option for low-volume road bridges

Skin-targeted inhibition of PPAR β/δ by selective antagonists to treat PPAR β/δ-mediated psoriasis-like skin disease in vivo

We have previously shown that peroxisome proliferator activating receptor ß/δ (PPAR β/δ is overexpressed in psoriasis. PPAR β/δ is not present in adult epidermis of mice. Targeted expression of PPAR β/δ and activation by a selective synthetic agonist is sufficient to induce an inflammatory skin disease resembling psoriasis. Several signalling pathways dysregulated in psoriasis are replicated in this model, suggesting that PPAR β/δ activation contributes to psoriasis pathogenesis. Thus, inhibition of PPAR β/δ might harbour therapeutical potential. Since PPAR β/δ has pleiotropic functions in metabolism, skin-targeted inhibition offer the potential of reducing systemic adverse effects. Here, we report that three selective PPAR β/δ antagonists, GSK0660, compound 3 h, and GSK3787 can be formulated for topical application to the skin and that their skin concentration can be accurately quantified using ultra-high performance liquid chromatography (UPLC)/mass spectrometry. These antagonists show efficacy in our transgenic mouse model in reducing psoriasis-like changes triggered by activation of PPAR β/δ. PPAR β/δ antagonists GSK0660 and compound 3 do not exhibit systemic drug accumulation after prolonged application to the skin, nor do they induce inflammatory or irritant changes. Significantly, the irreversible PPAR β/δ antagonist (GSK3787) retains efficacy when applied topically only three times per week which could be of practical clinical usefulness. Our data suggest that topical inhibition of PPAR β/δ to treat psoriasis may warrant further exploration

Assessment of metabolic and mitochondrial dynamics in CD4+ and CD8+ T cells in virologically suppressed HIV-positive individuals on combination antiretroviral therapy

Metabolism plays a fundamental role in supporting the growth, proliferation and effector functions of T cells. We investigated the impact of HIV infection on key processes that regulate glucose uptake and mitochondrial biogenesis in subpopulations of CD4+ and CD8+ T cells from 18 virologically-suppressed HIV-positive individuals on combination antiretroviral therapy (cART; median CD4+ cell count: 728 cells/μl) and 13 HIV seronegative controls. Mitochondrial membrane potential (MMP) and reactive oxygen species (ROS) production were also analysed in total CD4+ and CD8+ T cells. Among HIV+/cART individuals, expression of glucose transporter (Glut1) and mitochondrial density were highest within central memory and naïve CD4+ T cells, and lowest among effector memory and transitional memory T cells, with similar trends in HIV-negative controls. Compared to HIV-negative controls, there was a trend towards higher percentage of circulating CD4+Glut1+ T cells in HIV+/cART participants. There were no significant differences in mitochondrial dynamics between subject groups. Glut1 expression was positively correlated with mitochondrial density and MMP in total CD4+ T cells, while MMP was also positively correlated with ROS production in both CD4+ and CD8+ T cells. Our study characterizes specific metabolic features of CD4+ and CD8+ T cells in HIV-negative and HIV+/cART individuals and will invite future studies to explore the immunometabolic consequences of HIV infection

A multicenter comparison between Child Pugh and ALBI scores in patients treated with sorafenib for hepatocellular carcinoma

Background & aims: The ALBI grade was proposed as an objective means to evaluate liver function in patients with Hepatocellular Carcinoma (HCC). ALBI grade 1 vs 2 were proposed as stratification factors within the Child Pugh (CP) A class. However, the original publication did not provide comparison with the sub-classification by points (5 to 15) within the CP classification. Methods: We retrospectively analyzed data from patients treated with sorafenib for HCC from 17 centers in United Kingdom and France. Overall survival (OS) was analyzed with the Kaplan-Meier method and a Cox regression model. Discriminatory abilities of the classifications were assessed with the log likelihood ratio, Harrell’s C statistics and Akaike information criterion. Results: Data from 1,019 patients were collected, of which 905 could be assessed for both scores. 92% of ALBI grade 1 were CP A5 while ALBI 2 included a broad range of CP scores of which 44% were CP A6. Median OS was 10.2, 7.0 and 3.6 months for CP scores A5, A6 and >A6, respectively (P<0.001), Hazard Ratio (HR)=1.60 (95%CI: 1.35-1.89, P<0.001) for A6 vs A5. Median OS was 10.9, 6.6 and 3.0 months for ALBI grade 1, 2 and 3, respectively (P<0.001), HR=1.68 (1.43-1.97, P<0.001) for grade 2 vs 1. Discriminatory abilities of CP and ALBI were similar in the CP A population, but better for CP in the overall population. Conclusions: Our findings support the use CP class A as an inclusion criterion, and ALBI as a stratification factor in trials of systemic therapy

Orbital Instabilities in a Triaxial Cusp Potential

This paper constructs an analytic form for a triaxial potential that describes the dynamics of a wide variety of astrophysical systems, including the inner portions of dark matter halos, the central regions of galactic bulges, and young embedded star clusters. Specifically, this potential results from a density profile of the form $\rho (m) \propto m^{-1}$, where the radial coordinate is generalized to triaxial form so that $m^2 = x^2/a^2 + y^2/b^2 + z^2/c^2$. Using the resulting analytic form of the potential, and the corresponding force laws, we construct orbit solutions and show that a robust orbit instability exists in these systems. For orbits initially confined to any of the three principal planes, the motion in the perpendicular direction can be unstable. We discuss the range of parameter space for which these orbits are unstable, find the growth rates and saturation levels of the instability, and develop a set of analytic model equations that elucidate the essential physics of the instability mechanism. This orbit instability has a large number of astrophysical implications and applications, including understanding the formation of dark matter halos, the structure of galactic bulges, the survival of tidal streams, and the early evolution of embedded star clusters.Comment: 50 pages, accepted for publication in Ap

Stakeholders’ Perspectives on the Quality of End-of-Life Health Care Services for Chronic Obstructive Airways Disease: A Focus Group Study

Introduction: Delivery of end-of-life care for severe chronic obstructive pulmonary disease (COPD) has been hampered by an unpredictable disease trajectory and poor integration of health care and social services. Objective: To critically explore the perspectives, values, and experiences of stakeholders in COPD end-of-life healthcare services in a large district in Aotearoa New Zealand. Design: Focus groups analysed utilising critical theory and Actor-Network Theory. Methods: Stakeholders in end-of-life COPD healthcare services were purposively sampled from a large healthcare network in Canterbury, Aotearoa New Zealand to participate in seven focus groups (bereaved carers, community-based health professionals, non-Māori, non-Pacific patients, and support people (two groups), Māori patients, supporters and health professionals, Pacific patients, support people and health professionals, and hospital-based health professionals). Participants discussed end-of-life care services for people with COPD. Transcripts were coded utilising descriptive and structural coding to develop themes related to provision of quality care. Participants were positioned as experts. We considered how the themes arising supported and disrupted the healthcare network for end-of-life COPD. Results: Five themes related to quality of care for end-of-life COPD were identified: compassion, competence, community, commitment, and collaboration. The absence of any of these five themes required for quality care led to power imbalances within healthcare systems. Power inequities created disconnection among stakeholders which then disrupted commitment, community, and collaboration. A dysfunctional healthcare network impeded compassion between stakeholders and did not support their competence, leading to lower quality care. All five themes were identified as essential to delivery of high-quality end-of-life care in COPD. Conclusion: Stakeholders’ perspectives of end-of-life care for COPD identified of core features of a health system network that enabled or impeded the actions of stakeholders and allocation of resources to provide quality care

The dexamethasone suppression test as a predictor of sleep deprivation antidepressant effect

An abnormal dexamethasone suppression test (DST) result, a sensitive and specific marker for endogenous depression, was found to be associated with an antidepressant response to sleep deprivation in patients who met DSM-III criteria for Major Depressive Episode regardless of whether they met criteria for melancholia or psychotic subtypes of this disorder. These findings support previous reports of an association between an abnormal DST result and antidepressant effects of sleep deprivation in depressed patients. Our results extend the positive association between an abnormal DST result and the antidepressant response to sleep deprivation to include depressed patients who are clinically nonmelancholic during thair current episode but who have an abnormal DST result.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/23903/1/0000146.pd

Unintentionally retained vascular devices: improving recognition and removal

The increased demand for minimally invasive placement of intravascular medical devices has led to increased procedure-related complications, including retention of all or part of the implanted device. A number of risk factors can predispose to unintentionally retained vascular devices (uRVD); most are technical in etiology. Despite best efforts to insert and remove vascular devices properly, uRVD still occur. Prevention or early identification of uRVD is ideal; however, procedural complications are not always recognized at the time of device insertion or removal. In these cases, early radiologic diagnosis is important to enable expeditious removal and reduction of morbidity, mortality, and medicolegal consequences. The diagnostic radiologist’s role is to identify suspected uRVD and ensure proper communication of the findings to the referring clinician. The diagnostic radiologist can implement various strategies to increase detection of uRVD and advise the referring clinician regarding the use of minimally invasive percutaneous techniques for safe removal of uRVD

Structure of Metallathiacycles: Planar vs Nonplanar Geometries. A Theoretical and Experimental Investigation

Since the previously reported results of Fenske-Hall molecular orbital calculations suggested that the bent metallacycle geometries observed in transition-metal-inserted thiophene complexes do not result from electronic properties, molecular mechanics calculations were employed to explore how steric factors could influence ring geometries. These calculations have identified steric factors responsible for the observed ring deformations in (C 5 Me 5 )Rh(PMe 3 )(η 2 -C,S-2,5-Me 2 C 4 H 2 S) and benzothiophene and dibenzothiophene analogs. The results of the molecular mechanics calculations have been supported by X-ray structural characterization of the products formed via insertion of the reactive 16-electron metal fragment [(C 5 Me 5 )Rh(PMe 3 )] into the C-S bonds of unsubstituted thiophene, benzothiophene, and dibenzothiophene. The parent thiophene complex, unlike the previously reported ringsubstituted analog (and as predicted by the molecular mechanics calculations) is found to adopt a planar six-membered ring structure. The benzothiophene insertion product shows a moderate degree of bending of the metallathiacycle, whereas the dibenzothiophene molecule is strongly bent