Newborn screening (NBS) for cystic fibrosis (CF) is increasingly being implemented and is soon likely to be in use throughout the United States, because early detection permits access to specialized ...medical care and improves outcomes. The diagnosis of CF is not always straightforward, however. The sweat chloride test remains the gold standard for CF diagnosis but does not always give a clear answer. Genotype analysis also does not always provide clarity; more than 1500 mutations have been identified in the CF transmembrane conductance regulator (CFTR) gene, not all of which result in CF. Harmful mutations in the gene can present as a spectrum of pathology ranging from sinusitis in adulthood to severe lung, pancreatic, or liver disease in infancy. Thus, CF identified postnatally must remain a clinical diagnosis. To provide guidance for the diagnosis of both infants with positive NBS results and older patients presenting with an indistinct clinical picture, the Cystic Fibrosis Foundation convened a meeting of experts in the field of CF diagnosis. Their recommendations, presented herein, involve a combination of clinical presentation, laboratory testing, and genetics to confirm a diagnosis of CF.
Purpose This AUA Guideline focuses on evaluation/counseling and management of adult patients with clinically localized renal masses suspicious for cancer, including solid-enhancing tumors and Bosniak ...3/4 complex-cystic lesions. Materials and Methods Systematic review utilized research from the Agency for Healthcare Research and Quality and additional supplementation by the authors and consultant methodologists. Evidence-based statements were based on body of evidence strength Grade A/B/C (Strong/Moderate/Conditional Recommendations, respectively) with additional statements presented as Clinical Principles or Expert Opinions. Results Great progress has been made since the previous guidelines on management of localized renal masses was released (2009). The current guidelines provide updated, evidence-based recommendations regarding evaluation/counseling of patients with clinically localized renal masses, including the evolving role of renal mass biopsy. Given great variability of clinical, oncologic and functional characteristics, index patients are not utilized and the panel advocates individualized counseling/management. Management options (partial nephrectomy/radical nephrectomy/thermal ablation/active surveillance) are reviewed including recent data about comparative effectiveness and potential morbidities. Oncologic issues are prioritized while recognizing that functional outcomes are of great importance for survivorship for most patients with localized kidney cancer. A more restricted role for radical nephrectomy is recommended following well-defined selection criteria. Priority for partial nephrectomy is recommended for clinical T1a lesions, along with selective use of thermal ablation, particularly for tumors ≤3.0 cm. Important considerations for shared decision-making about active surveillance are explicitly defined. Conclusions Several factors should be considered during counseling/management of patients with clinically localized renal masses, including general health/comorbidities, oncologic potential of the mass, pertinent functional issues and relative efficacy/potential morbidities of various management strategies.
Identifying genetic biomarkers of synthetic lethal drug sensitivity effects provides one approach to the development of targeted cancer therapies. Mutations in ARID1A represent one of the most common ...molecular alterations in human cancer, but therapeutic approaches that target these defects are not yet clinically available. We demonstrate that defects in ARID1A sensitize tumour cells to clinical inhibitors of the DNA damage checkpoint kinase, ATR, both in vitro and in vivo. Mechanistically, ARID1A deficiency results in topoisomerase 2A and cell cycle defects, which cause an increased reliance on ATR checkpoint activity. In ARID1A mutant tumour cells, inhibition of ATR triggers premature mitotic entry, genomic instability and apoptosis. The data presented here provide the pre-clinical and mechanistic rationale for assessing ARID1A defects as a biomarker of single-agent ATR inhibitor response and represents a novel synthetic lethal approach to targeting tumour cells.
Molybdenum disulfide (MoS2) is a layered semiconducting material with a tunable bandgap that is promising for the next generation nanoelectronics as a substitute for graphene or silicon. Despite ...recent progress, the synthesis of high‐quality and highly uniform MoS2 on a large scale is still a challenge. In this work, a temperature‐dependent synthesis study of large‐area MoS2 by direct sulfurization of evaporated Mo thin films on SiO2 is presented. A variety of physical characterization techniques is employed to investigate the structural quality of the material. The film quality is shown to be similar to geological MoS2, if synthesized at sufficiently high temperatures (1050 °C). In addition, a highly uniform growth of trilayer MoS2 with an unprecedented uniformity of ±0.07 nm over a large area (> 10 cm2) is achieved. These films are used to fabricate field‐effect transistors following a straightforward wafer‐scale UV lithography process. The intrinsic field‐effect mobility is estimated to be about 6.5±2.2 cm2 V–1 s–1 and compared to previous studies. These results represent a significant step towards application of MoS2 in nanoelectronics and sensing.
A temperature‐dependent synthesis study of large‐area MoS2 by direct sulfurization of evaporated Mo thin films is presented. The resulting film quality is similar to geological MoS2. An unprecedented uniformity of ±0.07 nm over a large area (>10 cm2) is achieved with trilayer MoS2. The estimated intrinsic field‐effect mobility is approximately 6.5 ± 2.2 cm2 V–1 s–1.
Highly uniform large‐area MoS2 is chemically doped using molecular reductants and oxidants. Electrical measurements, photoemission, and Raman spectroscopy are used to study the doping effect and to ...understand the underlying mechanism. Strong work‐function changes of up to ±1 eV can be achieved, with contributions from state filling and surface dipoles. This results in high doping densities of up to ca. 8 × 1012 cm−2.
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A systematic review was conducted to evaluate the in vitro effects of nicotine on human gingival, periodontal ligament and oral epithelial cells, specifically: cell viability, cell ...attachment, cell proliferation and inflammatory mediator production.
This report followed the PRISMA statement. Two reviewers performed a literature search up to October 2018 in 3 databases: MEDLINE, EMBASE and Web of Science, supplemented by manual searching. Inclusion criteria comprised: in vitro studies evaluating human gingival fibroblasts, human periodontal ligament cells or human gingival/oral epithelial cells; nicotine exposure as a variable; including an appropriate control (no nicotine); published in English. Quality assessment was based on a 15-item checklist.
Of 356 potentially eligible studies, 42 were included. The median quality assessment score was 8/15. Study designs were highly heterogeneous. IC50 values for nicotine (exposure concentration causing 50% cell death or inhibition of cell growth or other utilised toxicity metric) derived from ten studies ranged from 6 μM to 25 mM. Studies investigating cell attachment, proliferation and inflammatory mediator production suggested that effects can be seen at a wide range of nicotine concentrations, but results were often contradictory.
According to findings from in vitro studies, nicotine, at levels found in tobacco smokers, nicotine replacement therapy users and e-cigarette users, is unlikely to be cytotoxic to human gingival and periodontal cells, though saliva levels in smokeless tobacco users may be high enough to achieve cytotoxicity. There was limited and contradictory evidence for nicotine effects on cell attachment, proliferation and inflammatory mediator production.
It is well established that whole tobacco smoke is highly damaging to oral tissues. The specific effects of nicotine are not well understood but are of increasing importance given the recent popularity of novel nicotine products. Increased knowledge on this topic will help to better inform dental professionals and patients.
Atomically thin molybdenum disulfide (MoS2) is a promising two-dimensional semiconductor for high-performance flexible electronics, sensors, transducers, and energy conversion. Here, piezoresistive ...strain sensing with flexible MoS2 field-effect transistors (FETs) made from highly uniform large-area films is demonstrated. The origin of the piezoresistivity in MoS2 is the strain-induced band gap change, which is confirmed by optical reflection spectroscopy. In addition, the sensitivity to strain can be tuned by more than 1 order of magnitude by adjusting the Fermi level via gate biasing.
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