Characteristics associated with significantly worse quality of life in mycosis fungoides/Sezary syndrome from the Prospective Cutaneous Lymphoma International Prognostic Index (PROCLIPI) study

Background Mycosis fungoides (MF) and Sezary Syndrome (SS) are the most common cutaneous T-cell lymphomas. MF/SS is accompanied by considerable morbidity from pain, itching and disfigurement. Aim To identify factors associated with poorer health-related quality of life (HRQoL) in patients newly diagnosed with MF/SS. Methods Patients enrolled into Prospective Cutaneous Lymphoma International Prognostic Index (PROCLIPI; an international observational study in MF/SS) had their HRQoL assessed using the Skindex-29 questionnaire. Skindex-29 scores were analysed in relation to patient- and disease-specific characteristics. Results The study population consisted of 237 patients [60 center dot 3% male; median age 60 years, (interquartile range 49-70)], of whom 179 had early MF and 58 had advanced MF/SS. In univariate analysis, HRQoL, as measured by Skindex-29, was worse in women, SS, late-stage MF, those with elevated lactate dehydrogenase, alopecia, high modified Severity Weighted Assessment Tool and confluent erythema. Linear regression models only identified female gender (beta = 8 center dot 61; P = 0 center dot 003) and alopecia (beta = 9 center dot 71, P = 0 center dot 02) as independent predictors of worse global HRQoL. Item-level analysis showed that the severe impairment in symptoms [odds ratio (OR) 2 center dot 14, 95% confidence interval (CI) 1 center dot 19-3 center dot 89] and emotions (OR 1 center dot 88, 95% CI 1 center dot 09-3 center dot 27) subscale scores seen in women was caused by more burning/stinging, pruritus, irritation and greater feelings of depression, shame, embarrassment and annoyance with their diagnosis of MF/SS. Conclusions HRQoL is significantly more impaired in newly diagnosed women with MF/SS and in those with alopecia. As Skindex-29 does not include existential questions on cancer, which may cause additional worry and distress, a comprehensive validated cutaneous T-cell lymphoma-specific questionnaire is urgently needed to more accurately assess disease-specific HRQoL in these patients.Peer reviewe

The techno-ecological practice as the politics of ontological coalitions

The paper focuses on the art projects aimed at visualizing (grasping) the physical or biological phenomena through interfaces and / or installations designed specifically for such purpose. Such works often mirror the post-­digital condition of our time where the digital technologies constitute the common background for everyday activities, no longer having the allure of "new" and "exciting" (Berry, Dieter et al., 2015). In this process, both the networked technologies of wireless communication and the act of crossing the boundaries between the digital and the physical play the crucial role as the post-­digital networked imagery increasingly becomes directly connected to the physical environment. I would like to ponder on the questions of processuality and relationality involved in such instances where the complexity of the hybrid works of art clearly transgresses the paradigm of representationalism (Thrift, 2008;; Anderson and Harrison, 2010;; Kember and Zylinska, 2012). The particular attention is given to the fact that such artworks bond different ontological realms (discursive, physical, digital) and different agents (human and non-­human, carbon-­based and software-­based) forging “ontological coalitions” (Malafouris, 2013). Throughout the article the mutlirealist and relational perspective is offered, inspired by the propositions of Gilbert Simondon and Etienne Souriau. Based on the research project supported by National Science Centre Poland ("The aesthetics of post-­digital imagery: between new materialism and object-­oriented philosophy", 2016/21/B/HS2/00746)

A phase I randomized therapeutic MVA-B vaccination improves the magnitude and quality of the T cell immune responses in HIV-1-infected subjects on HAART

Trial Design Previous studies suggested that poxvirus-based vaccines might be instrumental in the therapeutic HIV field. A phase I clinical trial was conducted in HIV-1-infected patients on highly active antiretroviral therapy (HAART), with CD4 T cell counts above 450 cells/mm3 and undetectable viremia. Thirty participants were randomized (2:1) to receive either 3 intramuscular injections of MVA-B vaccine (coding for clade B HIV-1 Env, Gag, Pol and Nef antigens) or placebo, followed by interruption of HAART. Methods The magnitude, breadth, quality and phenotype of the HIV-1-specific T cell response were assayed by intracellular cytokine staining (ICS) in 22 volunteers pre- and post-vaccination. Results MVA-B vaccine induced newly detected HIV-1-specific CD4 T cell responses and expanded pre-existing responses (mostly against Gag, Pol and Nef antigens) that were high in magnitude, broadly directed and showed an enhanced polyfunctionality with a T effector memory (TEM) phenotype, while maintaining the magnitude and quality of the pre-existing HIV-1- specific CD8 T cell responses. In addition, vaccination also triggered preferential CD8+ T cell polyfunctional responses to the MVA vector antigens that increase in magnitude after two and three booster doses

Contemporary genetic technologies and female reproduction

BACKGROUNDThe Fifth Evian Annual Reproduction (EVAR) Workshop Meeting discussed knowledge regarding contemporary genetics in female reproduction.METHODSSpecialist reproductive medicine clinicians and geneticists delivered presentations based on published literature and current research. The content of this report is based on the expert presentations and subsequent group discussions that took place during this Workshop.RESULTSNumerous ovarian genes with a role in infertility have been identified. Future challenges for genetic screening of patients, such as those with polycystic ovary syndrome, primary ovarian insufficiency or endometriosis, include the identification of high-throughput strategies and how to apply these findings to infertile patients. The identification of high-quality embryos in IVF using objective technologies remains a high priority in order to facilitate single-embryo transfer. Gene expression profiling of cumulus cells surrounding the oocyte, and proteomic and metabolomic approaches in embryo culture media may significantly improve non-invasive embryo quality assessment.CONCLUSIONSThe way forward in advancing the knowledge of genes involved in reproduction was considered to be through genome-wide association studies involving large numbers of patients. Establishing international collaboration is required to enable the application of such technologies in sufficient numbers of patients

The rice NLR pair Pikp-1/Pikp-2 initiates cell death through receptor cooperation rather than negative regulation

Plant NLR immune receptors are multidomain proteins that can function as specialized sensor/helper pairs. Paired NLR immune receptors are generally thought to function via negative regulation, where one NLR represses the activity of the second and detection of pathogen effectors relieves this repression to initiate immunity. However, whether this mechanism is common to all NLR pairs is not known. Here, we show that the rice NLR pair Pikp-1/Pikp-2, which confers resistance to strains of the blast pathogen Magnaporthe oryzae (syn. Pyricularia oryzae) expressing the AVR-PikD effector, functions via receptor cooperation, with effector-triggered activation requiring both NLRs to trigger the immune response. To investigate the mechanism of Pikp-1/Pikp-2 activation, we expressed truncated variants of these proteins, and made mutations in previously identified NLR sequence motifs. We found that any domain truncation, in either Pikp-1 or Pikp-2, prevented cell death in the presence of AVR-PikD, revealing that all domains are required for activity. Further, expression of individual Pikp-1 or Pikp-2 domains did not result in cell death. Mutations in the conserved P-loop and MHD sequence motifs in both Pikp-1 and Pikp-2 prevented cell death activation, demonstrating that these motifs are required for the function of the two partner NLRs. Finally, we showed that Pikp-1 and Pikp-2 associate to form homo- and hetero-complexes in planta in the absence of AVR-PikD; on co-expression the effector binds to Pikp-1 generating a tri-partite complex. Taken together, we provide evidence that Pikp-1 and Pikp-2 form a fine-tuned system that is activated by AVR-PikD via receptor cooperation rather than negative regulation

Buried Versus Exposed Kirschner Wires Following Fixation of Hand Fractures: l Clinician and Patient Surveys

Background: Fractures of the metacarpals and phalanges are common. Placement of Kirschner wires (K-wires) is the most common form of surgical fixation. After placement, a key decision is whether to bury the end of a K-wire or leave it protruding from the skin (exposed). A recent systematic review found no evidence to support either approach. The aim of study was to investigate current clinical practice, understand the key factors influencing clinician decision-making, and explore patient preferences to inform the design of a randomized clinical trial. Methods: The steering group developed surveys for hand surgeons, hand therapists, and patients. Following piloting, they were distributed across the United Kingdom hand surgery units using the Reconstructive Surgery Trials Network. Results: A total of 423 hand surgeons, 187 hand therapists, and 187 patients completed the surveys. Plastic surgeons and junior surgical trainees preferred to leave K-wires not buried. Ease of removal correlated with a decision to leave wires exposed, whereas perceived risk of infection correlated with burying wires. Cost did not affect the decision. Hand therapists were primarily concerned about infection and patient-related outcomes. Patients were most concerned about wire-related problems and pain. Conclusion: This national survey provides a new understanding of the use of K-wires to manage hand fractures in the United Kingdom. A number of nonevidence-based factors seem to influence the decision to bury or leave K-wires exposed. The choice has important clinical and health economic implications that justify a randomized controlled trial

Biological versus chronological ovarian age:implications for assisted reproductive technology

<p>Abstract</p> <p>Background</p> <p>Women have been able to delay childbearing since effective contraception became available in the 1960s. However, fertility decreases with increasing maternal age. A slow but steady decrease in fertility is observed in women aged between 30 and 35 years, which is followed by an accelerated decline among women aged over 35 years. A combination of delayed childbearing and reduced fecundity with increasing age has resulted in an increased number and proportion of women of greater than or equal to 35 years of age seeking assisted reproductive technology (ART) treatment.</p> <p>Methods</p> <p>Literature searches supplemented with the authors' knowledge.</p> <p>Results</p> <p>Despite major advances in medical technology, there is currently no ART treatment strategy that can fully compensate for the natural decline in fertility with increasing female age. Although chronological age is the most important predictor of ovarian response to follicle-stimulating hormone, the rate of reproductive ageing and ovarian sensitivity to gonadotrophins varies considerably among individuals. Both environmental and genetic factors contribute to depletion of the ovarian oocyte pool and reduction in oocyte quality. Thus, biological and chronological ovarian age are not always equivalent. Furthermore, biological age is more important than chronological age in predicting the outcome of ART. As older patients present increasingly for ART treatment, it will become more important to critically assess prognosis, counsel appropriately and optimize treatment strategies. Several genetic markers and biomarkers (such as anti-Müllerian hormone and the antral follicle count) are emerging that can identify women with accelerated biological ovarian ageing. Potential strategies for improving ovarian response include the use of luteinizing hormone (LH) and growth hormone (GH). When endogenous LH levels are heavily suppressed by gonadotrophin-releasing hormone analogues, LH supplementation may help to optimize treatment outcomes for women with biologically older ovaries. Exogenous GH may improve oocyte development and counteract the age-related decline of oocyte quality. The effects of GH may be mediated by insulin-like growth factor-I, which works synergistically with follicle-stimulating hormone on granulosa and theca cells.</p> <p>Conclusion</p> <p>Patients with biologically older ovaries may benefit from a tailored approach based on individual patient characteristics. Among the most promising adjuvant therapies for improving ART outcomes in women of advanced reproductive age are the administration of exogenous LH or GH.</p