MicroBooNE and the ν_{e} Interpretation of the MiniBooNE Low-Energy Excess.

A new generation of neutrino experiments is testing the 4.7σ anomalous excess of electronlike events observed in MiniBooNE. This is of huge importance for particle physics, astrophysics, and cosmology, not only because of the potential discovery of physics beyond the standard model, but also because the lessons we will learn about neutrino-nucleus interactions will be crucial for the worldwide neutrino program. MicroBooNE has recently released results that appear to disfavor several explanations of the MiniBooNE anomaly. Here, we show quantitatively that MicroBooNE results, while a promising start, unquestionably do not probe the full parameter space of sterile neutrino models hinted at by MiniBooNE and other data, nor do they probe the ν_{e} interpretation of the MiniBooNE excess in a model-independent way.

Quality of life and clinical characteristics of self-improving congenital ichthyosis within the disease spectrum of autosomal-recessive congenital ichthyosis.

BACKGROUND: Autosomal-recessive congenital ichthyosis (ARCI) is a heterogeneous group of ichthyoses presenting at birth. Self-improving congenital ichthyosis (SICI) is a subtype of ARCI and is diagnosed when skin condition improves remarkably (within years) after birth. So far, there are sparse data on SICI and quality of life (QoL) in this ARCI subtype. This study aims to further delineate the clinical spectrum of SICI as a rather unique subtype of ARCI. OBJECTIVES: This prospective study included 78 patients (median age: 15 years) with ARCI who were subdivided in SICI (n = 18) and non-SICI patients (nSICI, n = 60) by their ARCI phenotype. METHODS: Quality of life (QoL) was assessed using the (Children's) Dermatology Life Quality Index. Statistical analysis was performed with chi-squared and t-Tests. RESULTS: The genetically confirmed SICI patients presented causative mutations in the following genes: ALOXE3 (8/16; 50.0%), ALOX12B (6/16; 37.5%), PNPLA1 (1/16; 6.3%) and CYP4F22 (1/16; 6.3%). Hypo-/anhidrosis and insufficient vitamin D levels (<30 ng/mL) were often seen in SICI patients. Brachydactyly (a shortening of the 4th and 5th fingers) was statistically more frequent in SICI (P = 0.023) than in nSICI patients. A kink of the ear's helix was seen in half of the SICI patients and tends to occur more frequently in patients with ALOX12B mutations (P = 0.005). QoL was less impaired in patients under the age of 16, regardless of ARCI type. CONCLUSIONS: SICI is an underestimated, milder clinical variant of ARCI including distinct features such as brachydactyly and kinking of the ears. Clinical experts should be aware of these features when seeing neonates with a collodion membrane. SICI patients should be regularly checked for clinical parameters such as hypo-/anhidrosis or vitamin D levels and monitored for changes in quality of life.

High rate of self-improving phenotypes in children with non-syndromic congenital ichthyosis: case series from south-western Germany.

BACKGROUND: Non-syndromic congenital ichthyosis describes a heterogeneous group of hereditary skin disorders associated with erythroderma and scaling at birth. Although both severe and mild courses are known, the prediction of the natural history in clinical practice may be challenging. OBJECTIVES: To determine clinical course and genotype-phenotype correlations in children affected by non-syndromic congenital ichthyosis in a case series from south-western Germany. METHODS: We performed a retrospective observational study of 32 children affected by non-syndromic congenital ichthyoses seen in our genodermatosis clinic between 2011 and 2020. Follow-ups included assessment of weight and severity of skin involvement utilizing a modified Ichthyosis Area Severity Index (mIASI). mIASI was calculated as a sum comprising the previously published IASI score and an additional novel score to evaluate palmoplantar involvement. Linear regression was assessed using Pearson correlation, and statistical analysis was performed using the Wilcoxon-Mann-Whitney test. RESULTS: This study included 23 patients with autosomal recessive congenital ichthyosis, seven with keratinopathic ichthyosis and two with harlequin ichthyosis. Cutaneous manifestations improved in more than 70% of the children during the follow-up. Especially in patients with mutations in ALOXE3 and ALOX12B, mIASI scores dropped significantly. The most common phenotype observed in this study was designated 'mild fine scaling ichthyosis'. Severe palmoplantar involvement occurred in patients with KRT1 and ABCA12 mutations; most patients demonstrated hyperlinearity as a sign of dryness and scaling. Weight was mainly in the normal range and negatively correlated with the severity of skin involvement. CONCLUSIONS: Congenital ichthyosis that self-improves and evolves with mild fine scaling ichthyosis was the most common phenotype observed in our patients. This type might be underdiagnosed if the genetic diagnosis is not performed in the first year of life. mIASI is an easy and fast instrument for scoring disease severity and adding additional points for palmoplantar involvement might be valuable.

New opportunities at the next-generation neutrino experiments I: BSM neutrino physics and dark matter.

The combination of the high intensity proton beam facilities and massive detectors for precision measurements of neutrino oscillation parameters including the charge-parity violating (CPV) phase will open the door to help make beyond the standard model (BSM) physics reachable even in low energy regimes in the accelerator-based experiments. Large-mass detectors with highly precise tracking and energy measurements, excellent timing resolution, and low energy thresholds will enable the searches for BSM phenomena from cosmogenic origin, as well. Therefore, it is also conceivable that BSM topics in the next-generation neutrino experiments could be the dominant physics topics in the foreseeable future, as the precision of the neutrino oscillation parameter and CPV measurements continue to improve.This paper provides a review of the current landscape of BSM theory in neutrino experiments in two selected areas of the BSM topics-dark matter and neutrino related BSM-and summarizes the current results from existing neutrino experiments to set benchmarks for both theory and experiment. This paper then provides a review of upcoming neutrino experiments throughout the next 10 to 15 year time scale and their capabilities to set the foundation for potential reach in BSM physics in the two aforementioned themes. An important outcome of this paper is to ensure theoretical and simulation tools exist to carry out studies of these new areas of physics, from the first day of the experiments, such as Deep Underground Neutrino Experiment in the U.S. and Hyper-Kamiokande Experiment in Japan.

68Ga-PSMA PET/CT based primary staging and histological correlation after extended pelvic lymph node dissection at radical prostatectomy.

INTRODUCTION: Prostate-specific membrane antigen positron emission tomography-computed tomography (PSMA PET/CT) represents the upcoming standard for the staging of prostate cancer (PCa). However, there is still an unmet need for the validation of PSMA PET/CT at primary staging and consecutive histological correlation. Consequently, we decided to analyze the prediction parameter of PSMA PET/CT at primary staging. METHODS: We relied on 90 ≥ intermediate-risk PCa patients treated with radical prostatectomy (RP) and extended pelvic lymph node dissection. All patients were administered to 68Ga-PSMA PET/CT prior to surgery. 68Ga-PSMA PET/CT data were retrospectively reevaluated by a single radiologist and consequently compared to histological results from RP. Sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) for the detection of lymph node metastases were analyzed per-patient (n = 90), per-pelvic side (n = 180), and per-anatomic-region (external iliac artery and vein left/right vs. obturator fossa left/right vs. internal iliac artery left/right) (n = 458), respectively. RESULTS: Sensitivity, specificity, PPV, and NPV per-patient were: 43.8, 96.0, 70.0, and 88.8%, respectively. Sensitivity, specificity, PPV, and NPV per-pelvic-side were: 42.9, 95.6, 56.3, and 92.7%, respectively. Sensitivity, specificity, PPV, and NPV per-anatomic-region were: 47.6, 98.9, 66.7, and 97.5%, respectively. CONCLUSIONS: Negative 68Ga-PSMA PET/CT results were highly reliable in our study. Positive 68Ga-PSMA PET/CT results, however, revealed less reliable results. Larger and ideally prospective trials are justified to clarify the potential role of PSMA PET/CT based primary staging.

Arsenic-containing hydrocarbons: effects on gene expression, epigenetics, and biotransformation in HepG2 cells.

Arsenic-containing hydrocarbons (AsHCs), a subgroup of arsenolipids found in fish and algae, elicit substantial toxic effects in various human cell lines and have a considerable impact on cellular energy levels. The underlying mode of action, however, is still unknown. The present study analyzes the effects of two AsHCs (AsHC 332 and AsHC 360) on the expression of 44 genes covering DNA repair, stress response, cell death, autophagy, and epigenetics via RT-qPCR in human liver (HepG2) cells. Both AsHCs affected the gene expression, but to different extents. After treatment with AsHC 360, flap structure-specific endonuclease 1 (FEN1) as well as xeroderma pigmentosum group A complementing protein (XPA) and (cytosine-5)-methyltransferase 3A (DNMT3A) showed time- and concentration-dependent alterations in gene expression, thereby indicating an impact on genomic stability. In the subsequent analysis of epigenetic markers, within 72 h, neither AsHC 332 nor AsHC 360 showed an impact on the global DNA methylation level, whereas incubation with AsHC 360 increased the global DNA hydroxymethylation level. Analysis of cell extracts and cell media by HPLC-mass spectrometry revealed that both AsHCs were considerably biotransformed. The identified metabolites include not only the respective thioxo-analogs of the two AsHCs, but also several arsenic-containing fatty acids and fatty alcohols, contributing to our knowledge of biotransformation mechanisms of arsenolipids.

Reevaluation of the diametral compression test for tablets using the flattened disc geometry.

Mechanical strength is an important critical quality attribute for tablets. It is classically measured, in the pharmaceutical field, using the diametral compression test. Nevertheless, due to small contact area between the tablet and the platens, some authors suggested that during the test, the failure could occur in tension away from the center which would invalidate the test and the calculation of the tensile strength. In this study, the flattened disc geometry was used as an alternative to avoid contact problems. The diametral compression on both flattened and standard geometries was first studied using finite element method (FEM) simulation. It was found that, for the flattened geometry, both maximum tensile strain and stress were located at the center of the tablet, which was not the case for the standard geometry. Experimental observations using digital image correlation (DIC) confirmed the numerical results. The experimental tensile strength obtained using both geometries were compared and it was found that the standard geometry always gave lower tensile strength than the flattened geometry. Finally, high-speed video capture of the test made it possible to detect that for the standard geometry the crack initiation was always away from the center of the tablet.

Recent progress in the pathophysiology and treatment of FSGS recurrence.

Focal segmental glomerulosclerosis (FSGS) is a glomerular disease characterized by proteinuria, frequent progression to end-stage renal disease, and recurrence after kidney transplantation in ∼25% of patients, which negatively impacts long-term allograft survival. Experimental studies suggest that abnormalities in T and, possibly, B cells may represent one initial pathogenic trigger, leading to podocyte injury and progressive loss. New data also support the existence of circulating permeability factors able to damage the podocytes, but no single molecule has been consistently identified as the causal pathogenic element in FSGS recurrence. Unfortunately, major progress from mechanistic studies has not translated into substantial advancements in patient treatment, with plasmapheresis (PP) and high doses of cyclosporine (CsA) remaining the mainstays of therapy. Despite consistent experimental and clinical evidence that treatment of proteinuria slows renal function decline in proteinuric nephropathies, maximal use of antiproteinuric agents such as renin angiotensin system antagonists is not routine in the management of FSGS recurrence. More recently, encouraging results have been reported with anti-CD20 depleting antibody rituximab, but further studies are needed to establish its safety/efficacy profile.

Fast screening of solid electrolytes: a high throughput solid state NMR probe.

In this article we describe the construction of a high throughput solid state NMR probe for a fast and reliable determination of the NMR line width of a given nuclear species within a solid material. Since the NMR line width scales with the inverse of the mobility of the studied species and hence its ionic conductivity, this approach allows a fast screening of the material's promise as a solid electrolyte. The functionality of the approach is exemplified by the determination of the (7)Li-NMR line width of a set of 30 different liquid and solid Li-containing samples.

Postoperative insole-paedobarographic gait analysis for patients with flap coverages of weight-bearing and non-weight-bearing areas of the foot.

Functional results regarding shoe modifications, gait analysis and long-term durability of the reconstructed foot have not been reported using insole paedobarography. This article presents insole-paedobarographic gait analysis and discusses the various pressure distribution patterns following the reconstruction of the foot. This retrospective study reports on the clinical and functional results in 23 out of 39 patients who received flap coverage of their feet in our department in the period from 2001 to 2010. Mean follow-up time amounted to 46.6 months. Patients were separated into two groups, those with flap coverage to the sole of the foot (group 1) and those with flap coverage to non-weight-bearing areas of the foot (group 2). Gait analysis was accomplished by using insole paedobarography. The results of the gait analysis have shown that in both patient groups, when comparing affected feet with sound feet, the affected feet were exposed to significantly less support time (group 1; affected vs. sound feet: 0.44 ± 0.07 s vs. 0.55 ± 0.11 s, p = 0.047), (group 2; affected vs. sound feet: 0.47 ± 0.07 s vs. 0.54 ± 0.07 s, p = 0.029). In addition, in both patient groups, the analysis of peak-pressure distributions revealed greater pressures on the affected feet compared to the sound feet (group 1; affected vs. sound feet: 47.9 ± 10.13 N cm(-2) vs. 36.3 ± 7.5 N cm(-2), p = 0.008), (group 2; affected vs. sound feet: 38.08 ± 13.98 N cm(-2) vs. 32.92 ± 14.77 N cm(-2), p = 0.061). The insole paedobarography can contribute to a more precise gait analysis following a soft-tissue reconstruction not only of the sole but also of other foot regions as well. It can help to identify and correct movement sequences and peak-pressure distributions which are damaging to the flaps. The resulting potential minimisation of the ulceration rate can lead to a further optimisation in the rate of completely rehabilitated patients and a reduction in the revision rate.

Allogeneic gene-modified tumor cells (RCC-26/IL-7/CD80) as a vaccine in patients with metastatic renal cell cancer: a clinical phase-I study.

Despite novel targeted agents, prognosis of metastatic renal cell cancer (RCC) remains poor, and experimental therapeutic strategies are warranted. Transfection of tumor cells with co-stimulatory molecules and/or cytokines is able to increase immunogenicity. Therefore, in our clinical study, 10 human leukocyte antigen (HLA)-A(*)0201(+) patients with histologically-confirmed progressive metastatic clear cell RCC were immunized repetitively over 22 weeks with 2.5-40 × 10(6) interleukin (IL)-7/CD80 cotransfected allogeneic HLA-A(*)0201(+) tumor cells (RCC26/IL-7/CD80). Endpoints of the study were feasibility, safety, immunological and clinical responses. Vaccination was feasible and safe. In all, 50% of the patients showed stable disease throughout the study; the median time to progression was 18 weeks. However, vaccination with allogeneic RCC26/IL-7/CD80 tumor cells was not able to induce TH1-polarized immune responses. A TH2 cytokine profile with increasing amounts of antigen-specific IL-10 secretion was observed in most of the responding patients. Interferon-γ secretion by patient lymphocytes upon antigen-specific and non-specific stimulation was substantially impaired, both before and during vaccination, as compared with healthy controls. This is possibly due to profound tumor-induced immunosuppression, which may prevent induction of antitumor immune responses by the gene-modified vaccine. Vaccination in minimal residual disease with concurrent depletion of regulatory cells might be one strategy to overcome this limitation.

[Procedure guideline for sentinel lymph node diagnosis]. / Verfahrensanweisung für die nuklearmedizinische Wächter-Lymphknoten-Diagnostik.

The authors present a procedure guideline for scintigraphic detection of sentinel lymph nodes in malignant melanoma and other skin tumours, in breast cancer, in head and neck cancer, and in prostate and penile carcinoma. Important goals of sentinel lymph node scintigraphy comprise reduction of the extent of surgery, lower postoperative morbidity and optimization of histopathological examination focussing on relevant lymph nodes. Sentinel lymph node scintigraphy itself does not diagnose tumorous lymph node involvement and is not indicated when lymph node metastases have been definitely diagnosed before sentinel lymph node scintigraphy. Procedures are compiled with the aim to reliably localise sentinel lymph nodes with a high detection rate typically in early tumour stages. Radiation exposure is low so that pregnancy is not a contraindication for sentinel lymph node scintigraphy. Even with high volumes of scintigraphic sentinel lymph node procedures surgeons, theatre staff and pathologists receive a radiation exposure <1 mSv/year so that they do not require occupational radiation surveillance.

Gallbladder metastasis from renal cell carcinoma mimicking acute cholecystitis.

Renal cell carcinoma constitutes about 3% of adult malignancies. It has a high metastatic potential associated with synchronous or metachronous metastatic disease. Further, it is known to metastasize mainly to the lung, bone, brain, liver, or adrenal glands. In very rare cases it can metastasize to the gallbladder mimicking acute cholecystitis on clinical exam. In this case we present a patient who developed a gallbladder metastasis five years after a renal cell carcinoma mimicking acute cholecystitis.

Introduction and methodology - Guidelines on Parenteral Nutrition, Chapter 1.

Guidelines for Parenteral Nutrition were prepared by the German Society for Nutritional Medicine (http://www.dgem.de/), in collaboration with other medical associations to provide guidance for quality assurance for parenteral nutrition (PN) practice, and to promoting health and quality of life of patients concerned. A coordination team proposed topics, working group leaders who along with working group members performed systematic literatur searches and drafted recommendations in a nominal group process. Recommendations were discussed and agreed upon in a structured consensus conference process, followed by a Delphi consensus. The current English version of the guidelines was written and updated during the period between the last quarter of 2007 and the first quarter of 2009. The recommendations of the guidelines should be reviewed, and if necessary updated five years after publication.

Post-malignancy irradiation ulcers with exposed alloplastic materials can be salvaged with topical negative pressure therapy (TNP).

AIM: The aim of this study was to salvage or to integrate exposed alloplastic meshes in post malignancy irradiated chronic wounds by using topical negative pressure (TNP) therapy together with staged debridement. METHODS: Three patients with secondarily exposed alloplastic meshes in irradiated non-healing wounds were treated by serial debridement and repeated topical negative pressure therapy until clean and vital wounds were achieved, followed by ultimate plastic coverage by a myocutaneous flap or split-thickness skin graft. The range of the follow-up period was from 18 to 36 months. RESULTS: After staged serial debridement and repeated vacuum treatment periods wounds were preconditioned in an acceptable fashion for ultimate plastic coverage. After the treatment with a myocutaneous flap or split-thickness skin graft all three patients achieved long-term stable wounds with no alloplastic mesh complication within the follow-up period. CONCLUSION: Computer-controlled TNP therapy (vacuum-assisted closure therapy) together with staged debridement can help to induce granulation tissue formation in irradiated wounds and allows integration of alloplastic materials into regenerating wounds after ablative oncologic surgery.

Liver fibrogenesis due to cholestasis is associated with increased Smad7 expression and Smad3 signaling.

BACKGROUND/AIMS: Profibrogenic TGF-beta signaling in hepatic stellate cells is modulated during transdifferentiation. Strategies to abrogate TGF-beta effects provide promising antifibrotic results, however, in vivo data regarding Smad activation during fibrogenesis are scarce. METHODS: Here, liver fibrosis was assessed subsequent to bile duct ligation by determining liver enzymes in serum and collagen deposition in liver tissue. Activated hepatic stellate cells were identified by immunohistochemistry and immunoblots for alpha smooth muscle actin. Cellular localization of Smad3 and Smad7 proteins was demonstrated by immunohistochemistry. RTPCR for Smad4 and Smad7 was conducted with total RNA and Northern blot analysis for Smad7 with mRNA. Whole liver lysates were prepared to detect Smad2/3/4 and phospho- Smad2/3 by Western blotting. RESULTS: Cholestasis induces TGF-beta signaling via Smad3 in vivo, whereas Smad2 phosphorylation was only marginally increased. Smad4 expression levels were unchanged. Smad7 expression was continuously increasing with duration of cholestasis. Hepatocytes of fibrotic lesions exhibited nuclear staining Smad3. In contrast to this, Smad7 expression was localized to activated hepatic stellate cells. CONCLUSIONS: Hepatocytes of damaged liver tissue display increased TGF-beta signaling via Smad3. Further, negative feedback regulation of TGF-beta signaling by increased Smad7 expression in activated hepatic stellate cells occurs, however does not interfere with fibrogenesis.

[De Quervain's stenosing tendovaginitis--one of the most common conditions affecting the hand]. / Erkennen Sie auf Anhieb die Tendovaginitis stenosans de Quervain?

De Quervain's stenosing tendovaginitis is an inflammation of the first dorsal compartment. It is considered to be one of the most common forms of inflammation of the tendon sheaths. The diagnosis is based on the case history and the clinical examination. Finkelstein's test is pathognomonic. Should conservative treatment not prove successful, the condition is readily amenable to surgical treatment.