Not All Antibodies Are Created Equal: Factors That Influence Antibody Mediated Rejection.

Consistent with Dr. Paul Terasaki's "humoral theory of rejection" numerous studies have shown that HLA antibodies can cause acute and chronic antibody mediated rejection (AMR) and decreased graft survival. New evidence also supports a role for antibodies to non-HLA antigens in AMR and allograft injury. Despite the remarkable efforts by leaders in the field who pioneered single antigen bead technology for detection of donor specific antibodies, a considerable amount of work is still needed to better define the antibody attributes that are associated with AMR pathology. This review highlights what is currently known about the clinical context of pre and posttransplant antibodies, antibody characteristics that influence AMR, and the paths after donor specific antibody production (no rejection, subclinical rejection, and clinical dysfunction with AMR)

How does the self-reported clinical management of patients with low back pain relate to the attitudes and beliefs of health care practitioners? A survey of UK general practitioners and physiotherapists

AbstractGuidelines for the management of low back pain (LBP) have existed for many years, but adherence to these by health care practitioners (HCPs) remains suboptimal. The aim of this study was to measure the attitudes, beliefs and reported clinical behaviour of UK physiotherapists (PTs) and general practitioners (GPs) about LBP and to explore the associations between these. A cross-sectional postal survey of GPs (n=2000) and PTs (n=2000) was conducted that included the Pain Attitudes and Beliefs Scale (PABT.PT), and a vignette of a patient with non-specific LBP (NSLBP) with questions asking about recommendations for work, activity and bedrest. Data from 1022 respondents (442 GPs and 580 PTs) who had recently treated patients with LBP were analysed. Although the majority of HCPs reported providing advice for the vignette patient that was broadly in line with guideline recommendations, 28% reported they would advise this patient to remain off work. Work advice was significantly related to the PABS.PT scores with higher biomedical (F1,986=77.5, p<0.0001) and lower behavioural (F1,981=31.9, p<0.001) scores associated with advice to remain off work. We have demonstrated that the attitudes and reported practice behaviour of UK GPs and PTs for patients with NSLBP are diverse. Many HCPs held the belief that LBP necessitates some avoidance of activities and work. The attitudes and beliefs of these HCPs were associated with their self-reported clinical behaviour regarding advice about work. Future studies need to investigate whether approaches aimed at modifying these HCP factors can lead to improved patient outcomes

The Glasgow outcome at discharge scale: an inpatient assessment of disability after brain injury

This study assesses the validity and reliability of the Glasgow Outcome at Discharge Scale (GODS), which is a tool that is designed to assess disability after brain injury in an inpatient setting. It is derived from the Glasgow Outcome Scale-Extended (GOS-E), which assesses disability in the community after brain injury. Inter-rater reliability on the GODS is high (quadratic-weighted kappa 0.982; 95% confidence interval [CI] 0.968, 0.996) as is concurrent validity with the Disability Rating Scale (DRS) (Spearman correlation −0.728; 95% CI −0.819, −0.601). The GODS is significantly associated with physical and fatigue subscales of the short form (SF)-36 in hospital. In terms of predictive validity the GODS is highly associated with the GOS-E after discharge (Spearman correlation 0.512; 95% CI 0.281, 0.687), with the DRS, and with physical, fatigue, and social subscales of the SF-36. The GODS is recommended as an assessment tool for disability after brain injury pre-discharge and can be used in conjunction with the GOS-E to monitor disability between hospital and the community

The Limits of Evaluating Sustainability

Designing technology with sustainability in mind is becoming more and more important, especially considering future scenarios of limited resources where the world’s current lifestyle of wasteful consumption needs to change. But how can researchers believably argue that their solutions are indeed sustainable? How can consumers and technology users reliably acquire, understand, and apply information about environmental sustainability? Those questions are difficult to answer, especially in research domains where the impact on sustainability is not immediately measurable, such as sustainable HCI. The evaluation of sustainability is an ongoing problem that is often glossed over, but we believe the community needs to intensify its efforts to articulate its evaluation methods to other disciplines and external stakeholders. Even if those disciplines and stakeholders understand the importance of designing for sustainability, we need convincing arguments – such as validation through thorough evaluations – to showcase why a specific design solution works in the real world. In this paper, we analyze this problem by highlighting examples of sustainable HCI research in which evaluation of sustainability failed. We also look at previous research that sought to address this issue and discuss how their solutions can be generalized – and when they might fail. While we do not have the final answer, our intention is to start a discussion as to why sustainable HCI research is oftentimes not doing enough to justify the validity of its solutions. We close our paper by suggesting a few examples of what we believe to be potential ways to address those issues and take action to improve the evaluation of sustainability

Effects of Exogenous Yeast and Bacteria on the Microbial Population Dynamics and Outcomes of Olive Fermentations.

In this study, we examined Sicilian-style green olive fermentations upon the addition of Saccharomyces cerevisiae UCDFST 09-448 and/or Pichia kudriazevii UCDFST09-427 or the lactic acid bacteria (LAB) Lactobacillus plantarum AJ11R and Leuconostoc pseudomesenteroides BGM3R. Olives containing S. cerevisiae UCDFST 09-448, a strain able to hydrolyze pectin, but not P. kudriazevii UCDFST 09-427, a nonpectinolytic strain, exhibited excessive tissue damage within 4 weeks. DNA sequencing of fungal internal transcribed spacer (ITS) regions and comparisons to a yeast-specific ITS sequence database remarkably showed that neither S. cerevisiae UCDFST 09-448 nor P. kudriazevii UCDFST 09-427 resulted in significant changes to yeast species diversity. Instead, Candida boidinii constituted the majority (&gt;90%) of the total yeast present, independent of whether S. cerevisiae or P. kudriazevii was added. By comparison, Lactobacillus species were enriched in olives inoculated with potential starter LAB L. plantarum AJ11R and L. pseudomesenteroides BGM3R according to community 16S rRNA gene sequence analysis. The bacterial diversity of those olives was significantly reduced and resembled control fermentations incubated for a longer period of time. Importantly, microbial populations were highly dynamic at the strain level, as indicated by the large variations in AJ11R and BGM3R cell numbers over time and reductions in the numbers of yeast isolates expressing polygalacturonase activity. These findings show the distinct effects of exogenous spoilage and starter microbes on indigenous communities in plant-based food fermentations that result in very different impacts on product quality. IMPORTANCE Food fermentations are subject to tremendous selective pressures resulting in the growth and persistence of a limited number of bacterial and fungal taxa. Although these foods are vulnerable to spoilage by unintended contamination of certain microorganisms, or alternatively, can be improved by the deliberate addition of starter culture microbes that accelerate or beneficially modify product outcomes, the impact of either of those microbial additions on community dynamics within the fermentations is not well understood at strain-specific or global scales. Herein, we show how exogenous spoilage yeast or starter lactic acid bacteria confer very different effects on microbial numbers and diversity in olive fermentations. Introduced microbes have long-lasting consequences and result in changes that are apparent even when levels of those inoculants and their major enzymatic activities decline. This work has direct implications for understanding bacterial and fungal invasions of microbial habitats resulting in pivotal changes to community structure and function

Human papillomavirus, p16 and p53 expression associated with survival of head and neck cancer

BACKGROUND: P16 and p53 protein expression, and high-risk human papillomavirus (HPV-HR) types have been associated with survival in head and neck cancer (HNC). Evidence suggests that multiple molecular pathways need to be targeted to improve the poor prognosis of HNC. This study examined the individual and joint effects of tumor markers for differences in predicting HNC survival. P16 and p53 expression were detected from formalin-fixed, paraffin-embedded tissues by immunohistochemical staining. HPV DNA was detected by PCR and DNA sequencing in 237 histologically confirmed HNC patients. RESULTS: Overexpression of p16 (p16+) and p53 (p53+) occurred in 38% and 48% of HNC tumors, respectively. HPV-HR was detected in 28% of tumors. Worse prognosis was found in tumors that were p53+ (disease-specific mortality: adjusted hazard ratios, HR = 1.9, 95% CI: 1.04-3.4) or HPV- (overall survival: adj. HR = 2.1, 1.1-4.3) but no association in survival was found by p16 status. Compared to the molecular marker group with the best prognosis (p16+/p53-/HPV-HR: referent), the p16-/p53+/HPV- group had the lowest overall survival (84% vs. 60%, p < 0.01; HR = 4.1, 1.7-9.9) and disease-specific survival (86% vs. 66%, p < 0.01; HR = 4.0, 1.5-10.7). Compared to the referent, the HRs of the other six joint biomarker groups ranged from 1.6-3.4 for overall mortality and 0.9-3.9 for disease-specific mortality. CONCLUSION: The p16/p53/HPV joint groups showed greater distinction in clinical outcomes compared to results based on the individual biomarkers alone. This finding suggests that assessing multiple molecular markers in HNC patients will better predict the diverse outcomes and potentially the type of treatment targeted to those markers

Complex Etiology Underlies Risk and Survival in Head and Neck Cancer Human Papillomavirus, Tobacco, and Alcohol: A Case for Multifactor Disease

Findings are inconsistent about whether tobacco, alcohol, and human papillomavirus (HPV) are two independent HNC risk factor groups that distinguish an infection-associated cancer from a tobacco/alcohol-associated HNC. We found that cancer in the oral cavity risk was greater in HPV-E6/E7 seropositive/heavy tobacco users (adjusted OR = 3.5) than in HPV-seronegative/heavy tobacco users (adjusted OR = 1.4); and HPV-seropositive/heavy alcohol users (adjusted OR = 9.8) had greater risk than HPV-seronegative/heavy alcohol users (adjusted OR = 3.1). In contrast, the risk of oropharyngeal cancer was greater in the HPV-seronegative/heavy tobacco (adjusted OR = 11.0) than in HPV-seropositive/heavy tobacco (adjusted OR = 4.7) users and greater in HPV-seronegative/heavy alcohol users (adjusted OR = 24.3) compared to HPV-seropositive/heavy alcohol users (adjusted OR = 8.5). Disease-specific and recurrence-free adjusted survival were significantly worse in oropharyngeal HPV-seronegative cases with no survival differences by HPV status seen in oral cavity cases. The association between tobacco/alcohol, HPV, and tumor site is complex. There appear to be distinct tumor site differences in the combined exposure risks, suggesting that different molecular pathways are involved

Impairment-targeted exercises for older adults with knee pain: protocol for a proof-of-principle study.

BACKGROUND: Exercise therapy for knee pain and osteoarthritis remains a key element of conservative treatment, recommended in clinical guidelines. Yet systematic reviews point to only modest benefits from exercise interventions.One reason for this might be that clinical trials tend to use a one-size-fits-all approach to exercise, effectively disregarding the details of their participants' clinical presentations. This uncontrolled before-after study (TargET-Knee-Pain) aims to test the principle that exercises targeted at the specific physical impairments of older adults with knee pain may be able to significantly improve those impairments. It is a first step towards testing the effectiveness of this more individually-tailored approach. METHODS/DESIGN: We aim to recruit 60 participants from an existing observational cohort of community-dwelling older adults with knee pain. Participants will all have at least one of the three physical impairments of weak quadriceps, a reduced range of knee flexion and poor standing balance. Each participant will be asked to undertake a programme of exercises, targeted at their particular combination and degree of impairment(s), over the course of twelve weeks. The exercises will be taught and progressed by an experienced physiotherapist, with reference to a "menu" of agreed exercises for each of the impairments, over the course of six fortnightly home visits, alternating with six fortnightly telephone calls. Primary outcome measures will be isometric quadriceps strength, knee flexion range of motion, timed single-leg standing balance and the "Four Balance Test Scale" at 12 weeks. Key secondary outcome measures will be self-reported levels of pain, stiffness and difficulties with day-to-day functional tasks (WOMAC). Outcome measures will be taken at three time-points (baseline, six weeks and twelve weeks) by a study nurse blinded to the exercise status of the participants. DISCUSSION: This study (TargET-Knee-Pain) is the first step towards exploring whether an impairment-targeted approach to exercise prescription for older adults with knee pain may have sufficient efficacy to warrant further testing. If warranted, future randomised clinical trials may compare this approach with more traditional one-size-fits-all exercise approaches. TRIAL REGISTRATION: Current Controlled Trials ISRCTN61638364.RIGHTS : This article is licensed under the BioMed Central licence at http://www.biomedcentral.com/about/license which is similar to the 'Creative Commons Attribution Licence'. In brief you may : copy, distribute, and display the work; make derivative works; or make commercial use of the work - under the following conditions: the original author must be given credit; for any reuse or distribution, it must be made clear to others what the license terms of this work are

Evidence for Vertical Transmission of HPV from Mothers to Infants

Few large studies have evaluated concordance based on a broad spectrum of human papillomavirus (HPV) types in oral and genital specimens of mothers and their recently born infants. This information is important in determining whether HPV vaccines administered prior to pregnancy may be useful for preventing vertical transmission. HPV DNA was positive in 30% of mothers and 1.5% of newborns. Maternal/newborn concordance (HPV+/+ or HPV−/−) was 71%. Among HPV DNA+ mothers, only 3% of their infants were DNA+ and only 1 pair had the same HPV type. Among HPV− women, 0.8% of infants were HPV+. HPV DNA detected in hospitalized newborns reflects current infection transmitted to infants during pregnancy or delivery. None of the mother/baby HPV DNA+ concordance pairs detected viral types found in HPV vaccines suggesting that vaccination prior to pregnancy is unlikely to be efficacious in preventing vertical transmission