Unraveling the Mechanisms of Cutaneous Graft-Versus-Host Disease

The skin is the most common target organ affected by graft-versus-host disease (GVHD), with severity and response to therapy representing important predictors of patient survival. Although many of the initiating events in GVHD pathogenesis have been defined, less is known about why treatment resistance occurs or why there is often a permanent failure to restore tissue homeostasis. Emerging data suggest that the unique immune microenvironment in the skin is responsible for defining location- and context-specific mechanisms of injury that are distinct from those involved in other target organs. In this review, we address recent advances in our understanding of GVHD biology in the skin and outline the new research themes that will ultimately enable design of precision therapies

Classifying Alarms: Seeking Durability, Credibility, Consistency, and Simplicity

Alongside the development and testing of new audible alarms intended to support International Electrotechnical Commission 60601-1-8, a global standard concerned with alarm safety, the categories of risk that the standard denotes require further thought and possible updating. In this article, we revisit the origins of the categories covered by the standard. These categories were based on the ways that tissue damage can be caused. We consider these categories from the varied professional perspectives of the authors: human factors, semiotics, clinical practice, and the patient or family (layperson). We conclude that while the categories possess many clinically applicable and defensible features from our range of perspectives, the advances in alarm design now available may allow a more flexible approach. We present a three-tier system with superordinate, basic, and subordinate levels that fit both within the thinking embodied in the current standard and possible new developments

Dendritic Cells Cross-Present Immunogenic Lentivector-Encoded Antigen from Transduced Cells to Prime Functional T Cell Immunity

Recombinant lentiviral vectors (LVs) are highly effective vaccination vehicles that elicit protective T cell immunity in disease models. Dendritic cells (DCs) acquire antigen at sites of vaccination and migrate to draining lymph nodes, where they prime vaccine-specific T cells. The potency with which LVs activate CD8+ T cell immunity has been attributed to the transduction of DCs at the immunization site and durable presentation of LV-encoded antigens. However, it is not known how LV-encoded antigens continue to be presented to T cells once directly transduced DCs have turned over. Here, we report that LV-encoded antigen is efficiently cross-presented by DCs in vitro. We have further exploited the temporal depletion of DCs in the murine CD11c.DTR (diphtheria toxin receptor) model to demonstrate that repopulating DCs that were absent at the time of immunization cross-present LV-encoded antigen to T cells in vivo. Indirect presentation of antigen from transduced cells by DCs is sufficient to prime functional effector T cells that control tumor growth. These data suggest that DCs cross-present immunogenic antigen from LV-transduced cells, thereby facilitating prolonged activation of T cells in the absence of circulating LV particles. These are findings that may impact on the future design of LV vaccination strategies

Comparing the Job Satisfaction and Intention to Leave of Different Categories of Health Workers in Tanzania, Malawi, and South Africa.

Job satisfaction is an important determinant of health worker motivation, retention, and performance, all of which are critical to improving the functioning of health systems in low- and middle-income countries. A number of small-scale surveys have measured the job satisfaction and intention to leave of individual health worker cadres in different settings, but there are few multi-country and multi-cadre comparative studies. The objective of this study was to compare the job satisfaction and intention to leave of different categories of health workers in Tanzania, Malawi, and South Africa. We undertook a cross-sectional survey of a stratified cluster sample of 2,220 health workers, 564 from Tanzania, 939 from Malawi, and 717 from South Africa. Participants completed a self-administered questionnaire, which included demographic information, a 10-item job satisfaction scale, and one question on intention to leave. Multiple regression was used to identify significant predictors of job satisfaction and intention to leave. There were statistically significant differences in job satisfaction and intention to leave between the three countries. Approximately 52.1% of health workers in South Africa were satisfied with their jobs compared to 71% from Malawi and 82.6% from Tanzania (χ2=140.3, p<0.001). 18.8% of health workers in Tanzania and 26.5% in Malawi indicated that they were actively seeking employment elsewhere, compared to 41.4% in South Africa (χ2=83.5, p<0.001). The country differences were confirmed by multiple regression. The study also confirmed that job satisfaction is statistically related to intention to leave. We have shown differences in the levels of job satisfaction and intention to leave between different groups of health workers from Tanzania, Malawi, and South Africa. Our results caution against generalising about the effectiveness of interventions in different contexts and highlight the need for less standardised and more targeted HRH strategies than has been practised to date

Dermatological remedies in the traditional pharmacopoeia of Vulture-Alto Bradano, inland southern Italy

Dermatological remedies make up at least one-third of the traditional pharmacopoeia in southern Italy. The identification of folk remedies for the skin is important both for the preservation of traditional medical knowledge and in the search for novel antimicrobial agents in the treatment of skin and soft tissue infection (SSTI). Our goal is to document traditional remedies from botanical, animal, mineral and industrial sources for the topical treatment of skin ailments. In addition to SSTI remedies for humans, we also discuss certain ethnoveterinary applications. Field research was conducted in ten communities in the Vulture-Alto Bradano area of the Basilicata province, southern Italy. We randomly sampled 112 interviewees, stratified by age and gender. After obtaining prior informed consent, we collected data through semi-structured interviews, participant-observation, and small focus groups techniques. Voucher specimens of all cited botanic species were deposited at FTG and HLUC herbaria located in the US and Italy. We report the preparation and topical application of 116 remedies derived from 38 plant species. Remedies are used to treat laceration, burn wound, wart, inflammation, rash, dental abscess, furuncle, dermatitis, and other conditions. The pharmacopoeia also includes 49 animal remedies derived from sources such as pigs, slugs, and humans. Ethnoveterinary medicine, which incorporates both animal and plant derived remedies, is addressed. We also examine the recent decline in knowledge regarding the dermatological pharmacopoeia. The traditional dermatological pharmacopoeia of Vulture-Alto Bradano is based on a dynamic folk medical construct of natural and spiritual illness and healing. Remedies are used to treat more than 45 skin and soft tissue conditions of both humans and animals. Of the total 165 remedies reported, 110 have never before been published in the mainland southern Italian ethnomedical literature

Costs associated with febrile neutropenia in solid tumor and lymphoma patients - an observational study in Singapore.

BackgroundThe primary objective was to describe the total direct inpatient costs among solid tumor and lymphoma patients with chemotherapy-induced febrile neutropenia (FN) and the factors that were associated with higher direct cost. The secondary objective was to describe the out-of-pocket patient payments and the factors that were associated with higher out-of-pocket patient payments.MethodsThis was a single-center observational study conducted at the largest cancer center in Singapore. All of the adult cancer patients hospitalized due to FN from 2009 to 2012 were studied. The primary outcomes were the total hospital cost and the out-of-pocket patient payments (adjusted by government subsidy) per FN episode. Univariate analysis and multiple linear regression were conducted to identify the factors associated with higher FN costs.ResultsThree hundred and sixty seven adult cancer patients were documented with FN-related hospitalizations. The mean total hospital cost was US$4,193 (95$3,779-4,607) and the mean out-of-pocket patient payment was US$2,230 (95$1,976-2,484), per FN episode. The factors associated with a higher total hospital cost were longer length of stay, severe sepsis, and lymphoma as underlying cancer. The out-of-pocket patient payment was positively associated with longer length of stay, severe sepsis, lymphoma diagnosed as underlying cancer, the therapeutic use of granulocyte colony-stimulating factor (GCSF), the private ward class, and younger patients.ConclusionsThe total hospital cost and out-of-pocket patient payments of FN management in lymphoma cases were substantial compared with other solid tumors. Factors associated with a higher FN management cost may be useful for developing appropriate strategies to reduce the cost of FN for cancer patients

Semi-analytical approach to magnetized temperature autocorrelations

The cosmic microwave background (CMB) temperature autocorrelations, induced by a magnetized adiabatic mode of curvature inhomogeneities, are computed with semi-analytical methods. As suggested by the latest CMB data, a nearly scale-invariant spectrum for the adiabatic mode is consistently assumed. In this situation, the effects of a fully inhomogeneous magnetic field are scrutinized and constrained with particular attention to harmonics which are relevant for the region of Doppler oscillations. Depending on the parameters of the stochastic magnetic field a hump may replace the second peak of the angular power spectrum. Detectable effects on the Doppler region are then expected only if the magnetic power spectra have quasi-flat slopes and typical amplitude (smoothed over a comoving scale of Mpc size and redshifted to the epoch of gravitational collapse of the protogalaxy) exceeding 0.1 nG. If the magnetic energy spectra are bluer (i.e. steeper in frequency) the allowed value of the smoothed amplitude becomes, comparatively, larger (in the range of 20 nG). The implications of this investigation for the origin of large-scale magnetic fields in the Universe are discussed. Connections with forthcoming experimental observations of CMB temperature fluctuations are also suggested and partially explored.Comment: 40 pages, 13 figure