The Equilibrium State of Molecular Regions in the Outer Galaxy

A summary of global properties and an evaluation of the equilibrium state of molecular regions in the outer Galaxy are presented from the decomposition of the FCRAO Outer Galaxy Survey and targeted 12CO and 13CO observations of four giant molecular cloud complexes. The ensemble of identified objects includes both small, isolated clouds and clumps within larger cloud complexes. 12CO velocity dispersions show little variation with cloud sizes for radii less than 10 pc. It is demonstrated that the internal motions of regions with molecular masses greater than 10**4 msuns are bound by self gravity, yet, the constituent clumps of cloud complexes and isolated molecular clouds with M < 10**3 msuns are not in self gravitational equilibrium. The required external pressures to maintain the equilibrium of this population are (1-2)x10**4 cm-3-K.Comment: To appear in ApJ, 32 pages, 13 figures, 2 table

Antiretroviral therapy immunologic non-response in a Brazilian population: association study using pharmaco- and immunogenetic markers

BACKGROUND: Antiretroviral therapy (ART) saved millions from HIV-1 infection and AIDS, but some patients do not experience adequate CD4+ T cells gain despite achieving viral suppression. The genetic component of this condition is not yet completely elucidated. OBJECTIVE: To identify predictive genetic markers of immune response to ART. METHODS: Case-control study. Out of 176 HIV-infected patients recruited in the city of Recife, Northeast Brazil, 67 patients with no immunologic response were the cases and the remaining 109 patients who responded were the controls. A set of 94 selected single nucleotide polymorphisms (SNPs) involved in antiretroviral drugs pharmacodynamic pathways and immune system homeostasis were genotyped, while the remaining 48 were ancestry informative markers (AIMs) for controlling for eventual hidden population structure. RESULTS: Male patients were overrepresented in non-responder group (p=0.01). Non-responders also started with lower absolute CD4+ T cell counts (p<0.001). We found five SNPs significantly associated with the outcome, being three more frequent in non-responders than responders: rs2243250 (IL4) A allele (p=0.04), rs1128503 (ABCB1) A allele (p=0.03) and rs707265 (CYP2B6) A allele (p=0.02), whereas the other two were less frequent in non-responders: rs2069762 (IL2) C allele (p=0.004) and rs4646437 (CYP3A4) A allele (p=0.04). CONCLUSION: Some significant univariate associations remained independently associated at multivariate survival analysis modeling, such as pre-treatment CD4+ T cells counts, IL2 and ABCB1 genotypes, and use of protease inhibitors, yielding a predictive model for the probability for immune response. More studies are needed to unravel the genetic basis of ART immunological non-response

Sentinel Lymph Node Biopsy Pathology and 2-Year Postsurgical Recurrence of Breast Cancer in Kenyan Women

Purpose: The goal of this study was to describe the pathologic findings and early follow-up experience of patients who underwent a sentinel lymph node biopsy (SLNB) at Aga Khan University Hospital (AKUH) between 2008 and 2017. Patients and Methods: We performed a retrospective analysis of women with breast cancer who underwent an SLNB at AKUH between 2008 and 2017. The SLNB was performed on patients with stage I and stage II breast cancer, and identification of the sentinel lymph node was made by radioactive tracer, blue dye, or both, per availability and surgeon preference. Demographic, surgical, and pathologic data, including immunohistochemistry of the surgical sample for estrogen receptor, progesterone receptor, and human epidermal growth factor receptor 2, were abstracted from the patient records. Follow-up data were available for a subset of patients. Results: Between 2008 and 2017, six surgeons performed SLNBs on 138 women, 129 of whom had complete records and were included in the study. Thirty-one of 129 (24%) had a positive SLNB, including 10 of 73 (14%) with stage I and 21 of 56 (38%) with stage II disease. Seventy-eight patients (60%) received systemic adjuvant chemotherapy and 79 (62%) received radiation therapy, and of the 102 patients who were estrogen receptor positive, 86 (85%) received endocrine therapy. Seventy-nine patients were observed for \u3e 2 years, and, of these, four (5.1%) had a regional recurrence. Conclusion: The SLNB positivity rates were similar to those of high-income country (HIC) cohorts. However, preliminary data suggest that recurrence rates are elevated at AKUH as compared with those of HIC cohorts, perhaps because of a lower use of radiotherapy and chemotherapy at AKUH compared with HIC cohorts or because of differences in the characteristics of the primary tumor in patients at AKUH as compared with those in HICs

Profiling quality of care for patients with chronic headache in three different German hospitals – a case study

BACKGROUND: Legal requirements for quality assurance in German rehabilitation hospitals include comparisons of providers. Objective is to describe and to compare outcome quality of care offered by three hospitals providing in-patient rehabilitative treatment exemplified for patients with chronic headache. METHODS: We performed a prospective three center observational study on patients suffering from chronic headache. Patients underwent interventions commonly used according to internal guidelines of the hospitals. Measurements were taken at three points in time (at admission, at discharge and 6 months after discharge). Indicators of outcome quality included pain intensity and frequency of pain, functional ability, depression, quality of life and health related behavior. Analyses of differences amongst the hospitals were adjusted by covariates due to case-mix situation. RESULTS: 306 patients from 3 hospitals were included in statistical analysis. Amongst the hospitals, patients differed significantly in age, education, diagnostic subgroups, beliefs, and with respect to some pain-related baseline values (covariates). Patients in all three hospitals benefited from intervention to a clinically relevant degree. At discharge from hospital, outcome quality differed significantly after adjustment according to case-mix only in terms of patients' global assessment of treatment results. Six months after discharge, the only detectable significant differences were for secondary outcomes like improved coping with stress or increased use of self-help. The profiles for satisfaction with the hospital stay showed clear differences amongst patients. CONCLUSION: The results of this case study do not suggest a definite overall ranking of the three hospitals that were compared, but outcome profiles offer a multilayer platform of reliable information which might facilitate decision making

Does minimally invasive lumbar disc surgery result in less muscle injury than conventional surgery? A randomized controlled trial

The concept of minimally invasive lumbar disc surgery comprises reduced muscle injury. The aim of this study was to evaluate creatine phosphokinase (CPK) in serum and the cross-sectional area (CSA) of the multifidus muscle on magnetic resonance imaging as indicators of muscle injury. We present the results of a double-blind randomized trial on patients with lumbar disc herniation, in which tubular discectomy and conventional microdiscectomy were compared. In 216 patients, CPK was measured before surgery and at day 1 after surgery. In 140 patients, the CSA of the multifidus muscle was measured at the affected disc level before surgery and at 1 year after surgery. The ratios (i.e. post surgery/pre surgery) of CPK and CSA were used as outcome measures. The multifidus atrophy was classified into three grades ranging from 0 (normal) to 3 (severe atrophy), and the difference between post and pre surgery was used as an outcome. Patients’ low-back pain scores on the visual analogue scale (VAS) were documented before surgery and at various moments during follow-up. Tubular discectomy compared with conventional microdiscectomy resulted in a nonsignificant difference in CPK ratio, although the CSA ratio was significantly lower in tubular discectomy. At 1 year, there was no difference in atrophy grade between both groups nor in the percentage of patients showing an increased atrophy grade (14% tubular vs. 18% conventional). The postoperative low-back pain scores on the VAS improved in both groups, although the 1-year between-group mean difference of improvement was 3.5 mm (95% CI; 1.4–5.7 mm) in favour of conventional microdiscectomy. In conclusion, tubular discectomy compared with conventional microdiscectomy did not result in reduced muscle injury. Postoperative evaluation of CPK and the multifidus muscle showed similar results in both groups, although patients who underwent tubular discectomy reported more low-back pain during the first year after surgery

Direct Ophthalmic Healthcare Resource Use among Geographic Atrophy Patients in a Large Cohort from the United Kingdom

Objective To estimate the direct ophthalmic health care resource use in patients with geographic atrophy (GA) secondary to age-related macular degeneration (AMD). Design Retrospective analysis of anonymized data derived from electronic medical records acquired at 10 clinical sites in the United Kingdom. Participants Patients aged ≥50 years with ≥1 eye with a clinical record of GA or, for comparison, bilateral early/intermediate AMD. Four subgroups were identified: GA in both eyes (GA : GA); GA in 1 eye, choroidal neovascularization (CNV) in the fellow eye (GA : CNV); GA in 1 eye with early or intermediate AMD in the fellow eye (GA : E); and early/intermediate AMD in both eyes (E : E). Methods Electronic medical records were analyzed to derive the median number of visits over the first 2 years following diagnosis of GA or early/intermediate AMD. Clinical tests recorded at visits were used to calculate estimated costs (payer perspective) of monitoring. Analyses were restricted to patients with an initial diagnosis on or after January 1, 2011 to represent present day monitoring and costs associated with AMD. Main Outcome Measures Median number of visits and estimated monitoring costs per patient (in £) over the first 2 years among patients with ≥2 years of follow-up and in the individual subgroups. Intravitreal treatment costs in the GA : CNV group were excluded. Results For all 3 GA subgroups (n = 1080), the median number of visits over the first 2 years was 5 and monitoring costs were £460.80 per patient. The GA : CNV subgroup (n = 355) had the highest number of visits (median, 15), with a cost of £1581, compared with the GA : E subgroup (n = 283; median 4 visits; cost ∼£369) and the GA : GA subgroup (n = 442; median 3 visits; cost ∼£277). Ophthalmic tests were conducted most frequently in the GA : CNV subgroup. Visits and costs in the E : E subgroup (n = 6079) were lower. Conclusions Resource use in patients with GA varies considerably and is strongly influenced by the concomitant presence of CNV and lack of monitoring strategies for GA

Growth rate after limb deformity correction by the Ilizarov method with or without knee joint distraction: Lengthening in 30 children followed for at least 2 years

Background and purpose Growth inhibition and stimulation have both been reported after juvenile limb lengthening. Distraction of a joint usually suspends and unloads the growth plate and may stimulate growth. We investigated the influence of knee joint distraction on the speed of growth after limb lengthening

The effect of forearm posture on wrist flexion in computer workers with chronic upper extremity musculoskeletal disorders

<p>Abstract</p> <p>Background</p> <p>Occupational computer use has been associated with upper extremity musculoskeletal disorders (UEMSDs), but the etiology and pathophysiology of some of these disorders are poorly understood. Various theories attribute the symptoms to biomechanical and/or psychosocial stressors. The results of several clinical studies suggest that elevated antagonist muscle tension may be a biomechanical stress factor. Affected computer users often exhibit limited wrist range of motion, particularly wrist flexion, which has been attributed to increased extensor muscle tension, rather than to pain symptoms. Recreational or domestic activities requiring extremes of wrist flexion may produce injurious stress on the wrist joint and muscles, the symptoms of which are then exacerbated by computer use. As these activities may involve a variety of forearm postures, we examined whether changes in forearm posture have an effect on pain reports during wrist flexion, or whether pain would have a limiting effect on flexion angle.</p> <p>Methods</p> <p>We measured maximum active wrist flexion using a goniometer with the forearm supported in the prone, neutral, and supine postures. Data was obtained from 5 subjects with UEMSDs attributed to computer use and from 13 control subjects.</p> <p>Results</p> <p>The UEMSD group exhibited significantly restricted wrist flexion compared to the control group in both wrists at all forearm postures with the exception of the non-dominant wrist with the forearm prone. In both groups, maximum active wrist flexion decreased at the supine forearm posture compared to the prone posture. No UEMSD subjects reported an increase in pain symptoms during testing.</p> <p>Conclusion</p> <p>The UEMSD group exhibited reduced wrist flexion compared to controls that did not appear to be pain related. A supine forearm posture reduced wrist flexion in both groups, but the reduction was approximately 100% greater in the UEMSD group. The effect of a supine forearm posture on wrist flexion is consistent with known biomechanical changes in the distal extensor carpi ulnaris tendon that occur with forearm supination. We infer from these results that wrist extensor muscle passive tension may be elevated in UEMSD subjects compared to controls, particularly in the extensor carpi ulnaris muscle. Measuring wrist flexion at the supine forearm posture may highlight flexion restrictions that are not otherwise apparent.</p

Guidelines for mouse and human DC functional assays

This article is part of the Dendritic Cell Guidelines article series, which provides a collection of state-of-the-art protocols for the preparation, phenotype analysis by flow cytometry, generation, fluorescence microscopy, and functional characterization of mouse and human dendritic cells (DC) from lymphoid organs and various non-lymphoid tissues. Recent studies have provided evidence for an increasing number of phenotypically distinct conventional DC (cDC) subsets that on one hand exhibit a certain functional plasticity, but on the other hand are characterized by their tissue- and context-dependent functional specialization. Here, we describe a selection of assays for the functional characterization of mouse and human cDC. The first two protocols illustrate analysis of cDC endocytosis and metabolism, followed by guidelines for transcriptomic and proteomic characterization of cDC populations. Then, a larger group of assays describes the characterization of cDC migration in vitro, ex vivo, and in vivo. The final guidelines measure cDC inflammasome and antigen (cross)-presentation activity. While all protocols were written by experienced scientists who routinely use them in their work, this article was also peer-reviewed by leading experts and approved by all co-authors, making it an essential resource for basic and clinical DC immunologists

Cost-effectiveness of decompression according to Gill versus instrumented spondylodesis in the treatment of sciatica due to low grade spondylolytic spondylolisthesis: A prospective randomised controlled trial [NTR1300]

Background. Nerve root decompression with instrumented spondylodesis is the most frequently performed surgical procedure in the treatment of patients with symptomatic low-grade spondylolytic spondylolisthesis. Nerve root decompression without instrumented fusion, i.e. Gill's procedure, is an alternative and less invasive approach. A comparative cost-effectiveness study has not been performed yet. We present the design of a randomised controlled trial on cost-effectiveness of decompression according to Gill versus instrumented spondylodesis. Methods/design. All patients (age between 18 and 70 years) with sciatica or neurogenic claudication lasting more than 3 months due to spondylolytic spondylolisthesis grade I or II, are eligible for inclusion. Patients will be randomly allocated to nerve root decompression according to Gill, either unilateral or bilateral, or pedicle screw fixation with interbody fusion. The main primary outcome measure is the functional assessment of the patient measured with the Roland Disability Questionnaire for Sciatica at 12 weeks and 2 years. Other primary outcome measures are perceived recovery and intensity of leg pain and low back pain. The secondary outcome measures include, incidence of re-operations, complications, serum creatine phosphokinase, quality of life, medical consumption, costs, absenteeism, work perception, depression and anxiety, and treatment preference. The study is a randomised prospective multicenter trial in which two surgical techniques are compared in a parallel group design. Patients and research nurse will not be blinded during the follow-up period of 2 years. Discussion. Currently, nerve root decompression with instrumented fusion is the golden standard in the surgical treatment of low-grade spondylolytic spondylolisthesis, although scientific proof justifying instrumented spondylodesis over simple decompression is lacking. This trial is designed to elucidate the controversy in best surgical treatment of symptomatic patients with low-