A translation and preliminary validation of the Dutch Wound-QoL questionnaire

Background: Chronic wounds have a major impact on patients' health-related quality of life (HRQoL). Therefore, measuring HRQoL is an indispensable part of the treatment of patients with chronic wounds. The aim of this study was to translate and validate the Wound-QoL, a wound-specific HRQoL questionnaire, in a Dutch population. Methods: The Wound-QoL was translated into Dutch according to the international standards. Patients with chronic wounds were asked to complete questionnaires at baseline (T0) and after six weeks (T1), including Wound-QoL, EQ-5D-3L (a generic questionnaire to measure HRQoL) and a visual analogue scale (VAS) measuring wound pain. If patients were not able to complete the questionnaire by themselves, it was read out to them by a nurse. Further data were obtained from medical records. Results: Of the 120 patients included, 64 (53.3%) completed the questionnaire by themselves. To 55 patients (45.8%), the questionnaire was read out. The internal consistency of the Wound-QoL global score was high at both time points (T0: Cronbach's α = 0.89, T1: Cronbach's α = 0.92). The item selectivity for global score ranged from r = 0.25 to r = 0.77 at T0 and from r = 0.40 to r = 0.79 at T1. Overall, the self-completion and read-out subgroups showed similar internal consistency and item selectivity scores. With regard to convergent validity, significant correlations were found between Wound-QoL and EQ-5D-3L (T0: r = - 0.45, p < 0.001, T1: r = - 0.50, p < 0.001) as well as between Wound-QoL and pain VAS (T0: r = 0.23, p = 0.012, T1: r = 0.37, p = 0.001) at both time points. Responsiveness analyses showed significant correlations between changes in Wound-QoL and changes in EQ-5D-3L (r = - 0.37, p < 0.001), pain VAS (r = 0.24, p = 0.044) and wound size (r = 0.24, p = 0.013). The self-completion and read-out subgroups showed differences in convergent validity and responsiveness. Conclusions: The results indicate that the Dutch version of the Wound-QoL has positive psychometric properties. However, more research is needed to further explore the differences between self-completed and read-out questionnaires

Multiwavelength Observations of Massive Stellar Cluster Candidates in the Galaxy

The Galaxy appears to be richer in young, massive stellar clusters than previously known, due to advances in infrared surveys which have uncovered deeply embedded regions of star formation. Young, massive clusters can significantly impact the surrounding interstellar medium (ISM) and hence radio observations can also be an important tracer of their activity. Several hundred cluster candidates are now known by examining survey data. Here we report on multiwavelength observations of six of these candidates in the Galaxy. We carried out 4.9 and 8.5 GHz VLA observations of the radio emission associated with these clusters to obtain the physical characteristics of the surrounding gas, including the Lyman continuum photon flux and ionized gas mass. Spitzer Infrared Array Camera observations were also made of these regions, and provide details on the stellar population as well as the dust continuum and polycyclic aromatic hydrocarbon emission. When compared to the known young, massive clusters in the Galaxy, the six cluster candidates have less powerful Lyman ionizing fluxes and ionize less of the H II mass in the surrounding ISM. Therefore, these cluster candidates appear to be more consistent with intermediate-mass clusters (10^3-10^4 Msun).Comment: 39 pages, 20 figures. Accepted in the Astronomical Journal; to be published Fall 201

High Mass Star Formation. II. The Mass Function of Submillimeter Clumps in M17

We have mapped an approximately 5.5 by 5.5 pc portion of the M17 massive star-forming region in both 850 and 450 micron dust continuum emission using the Submillimeter Common-User Bolometer Array (SCUBA) on the James Clerk Maxwell Telescope (JCMT). The maps reveal more than 100 dusty clumps with deconvolved linear sizes of 0.05--0.2 pc and masses of 0.8--120 solar masses, most of which are not associated with known mid-infrared point sources. Fitting the clump mass function with a double power law gives a mean power law exponent of alpha_high = -2.4 +/- 0.3 for the high-mass power law, consistent with the exponent of the Salpeter stellar mass function. We show that a lognormal clump mass distribution with a peak at about 4 solar masses produces as good a fit to the clump mass function as does a double power law. This 4 solar mass peak mass is well above the peak masses of both the stellar initial mass function and the mass function of clumps in low-mass star-forming regions. Despite the difference in intrinsic mass scale, the shape of the M17 clump mass function appears to be consistent with the shape of the core mass function in low-mass star-forming regions. Thus, we suggest that the clump mass function in high-mass star-forming regions may be a scaled-up version of that in low-mass regions, instead of its extension to higher masses.Comment: 33 pages, 6 figures, 3 tables. Accepted for publication in the Astrophysical Journa

Nomenclature of Genetically Determined Myoclonus Syndromes:Recommendations of the International Parkinson and Movement Disorder Society Task Force

Genetically determined myoclonus disorders are a result of a large number of genes. They have wide clinical variation and no systematic nomenclature. With next-generation sequencing, genetic diagnostics require stringent criteria to associate genes and phenotype. To improve (future) classification and recognition of genetically determined movement disorders, the Movement Disorder Society Task Force for Nomenclature of Genetic Movement Disorders (2012) advocates and renews the naming system of locus symbols. Here, we propose a nomenclature for myoclonus syndromes and related disorders with myoclonic jerks (hyperekplexia and myoclonic epileptic encephalopathies) to guide clinicians in their diagnostic approach to patients with these disorders. Sixty-seven genes were included in the nomenclature. They were divided into 3 subgroups: prominent myoclonus syndromes, 35 genes; prominent myoclonus syndromes combined with another prominent movement disorder, 9 genes; disorders that present usually with other phenotypes but can manifest as a prominent myoclonus syndrome, 23 genes. An additional movement disorder is seen in nearly all myoclonus syndromes: ataxia (n = 41), ataxia and dystonia (n = 6), and dystonia (n = 5). However, no additional movement disorders were seen in related disorders. Cognitive decline and epilepsy are present in the vast majority. The anatomical origin of myoclonus is known in 64% of genetic disorders: cortical (n = 34), noncortical areas (n = 8), and both (n = 1). Cortical myoclonus is commonly seen in association with ataxia, and noncortical myoclonus is often seen with myoclonus-dystonia. This new nomenclature of myoclonus will guide diagnostic testing and phenotype classification. (c) 2019 The Authors. Movement Disorders published by Wiley Periodicals, Inc. on behalf of International Parkinson and Movement Disorder Society

Educating Dairy and Beef Producers on Environmental Issues and Regulatory Concerns for Smaller Farms

Livestock producers in Iowa have seen a progression of regulations and compliance enforcement throughout the past two decades. Awareness through Extension meetings and information put out by commodity groups has played a substantial role in bringing confinement feeding operations and large CAFO feedlots into compliance. For small to medium-sized feedlots and dairies that may or may not be classified as CAFOs, the education and outreach was not formalized prior to the EPA beginning their recent compliance reviews. This issue surfaced because of EPA interpretation of regulations and the subsequent impact on livestock producers. The message from EPA was not well defined and still remains a challenge for livestock producers, extension personnel, and agribusiness (advisers) and agency staff

NEMO reshapes the α-Synuclein aggregate interface and acts as an autophagy adapter by co-condensation with p62

NEMO is a ubiquitin-binding protein which regulates canonical NF-kappa B pathway activation in innate immune signaling, cell death regulation and host-pathogen interactions. Here we identify an NF-kappa B-independent function of NEMO in proteostasis regulation by promoting autophagosomal clearance of protein aggregates. NEMO-deficient cells accumulate misfolded proteins upon proteotoxic stress and are vulnerable to proteostasis challenges. Moreover, a patient with a mutation in the NEMO-encoding IKBKG gene resulting in defective binding of NEMO to linear ubiquitin chains, developed a widespread mixed brain proteinopathy, including alpha-synuclein, tau and TDP-43 pathology. NEMO amplifies linear ubiquitylation at alpha-synuclein aggregates and promotes the local concentration of p62 into foci. In vitro, NEMO lowers the threshold concentrations required for ubiquitin-dependent phase transition of p62. In summary, NEMO reshapes the aggregate surface for efficient autophagosomal clearance by providing a mobile phase at the aggregate interphase favoring co-condensation with p62. Selective autophagy helps to degrade aggregated proteins accumulating in neurodegenerative diseases. Here, the authors show that NEMO, a ubiquitin binding protein previously linked to innate immune signaling, is recruited to misfolded proteins and promotes their autophagic clearance by forming condensates with the autophagy receptor p62

CAG Repeats Determine Brain Atrophy in Spinocerebellar Ataxia 17: A VBM Study

Abnormal repeat length has been associated with an earlier age of onset and more severe disease progression in the rare neurodegenerative disorder spinocerebellar ataxia 17 (SCA17).To determine whether specific structural brain degeneration and rate of disease progression in SCA17 might be associated with the CAG repeat size, observer-independent voxel-based morphometry was applied to high-resolution magnetic resonance images of 16 patients with SCA17 and 16 age-matched healthy controls. The main finding contrasting SCA17 patients with healthy controls demonstrated atrophy in the cerebellum bilaterally. Multiple regression analyses with available genetic data and also post-hoc correlations revealed an inverse relationship again with cerebellar atrophy. Moreover, we found an inverse relationship between the CAG repeat length and rate of disease progression.Our results highlight the fundamental role of the cerebellum in this neurodegenerative disease and support the genotype-phenotype relationship in SCA17 patients. Genetic factors may determine individual susceptibility to neurodegeneration and rate of disease progression

The price of tumor control: an analysis of rare side effects of anti-CTLA-4 therapy in metastatic melanoma from the ipilimumab network

Background: Ipilimumab, a cytotoxic T-lymphocyte antigen-4 (CTLA-4) blocking antibody, has been approved for the treatment of metastatic melanoma and induces adverse events (AE) in up to 64% of patients. Treatment algorithms for the management of common ipilimumab-induced AEs have lead to a reduction of morbidity, e.g. due to bowel perforations. However, the spectrum of less common AEs is expanding as ipilimumab is increasingly applied. Stringent recognition and management of AEs will reduce drug-induced morbidity and costs, and thus, positively impact the cost-benefit ratio of the drug. To facilitate timely identification and adequate management data on rare AEs were analyzed at 19 skin cancer centers. Methods and Findings: Patient files (n = 752) were screened for rare ipilimumab-associated AEs. A total of 120 AEs, some of which were life-threatening or even fatal, were reported and summarized by organ system describing the most instructive cases in detail. Previously unreported AEs like drug rash with eosinophilia and systemic symptoms (DRESS), granulomatous inflammation of the central nervous system, and aseptic meningitis, were documented. Obstacles included patientś delay in reporting symptoms and the differentiation of steroid-induced from ipilimumab-induced AEs under steroid treatment. Importantly, response rate was high in this patient population with tumor regression in 30.9% and a tumor control rate of 61.8% in stage IV melanoma patients despite the fact that some patients received only two of four recommended ipilimumab infusions. This suggests that ipilimumab-induced antitumor responses can have an early onset and that severe autoimmune reactions may reflect overtreatment. Conclusion: The wide spectrum of ipilimumab-induced AEs demands doctor and patient awareness to reduce morbidity and treatment costs and true ipilimumab success is dictated by both objective tumor responses and controlling severe side effects