This paper investigates the formation and evolution of deep convection inside the east-west oriented rainbands associated with a low-level jet (LLJ) in Typhoon Morakot (2009). With the typhoon center ...to the northwest of Taiwan, the westerly LLJ occurred as a result from the interaction of typhoon circulation with the southwest monsoon flow, which supplied the water vapor for the extreme rainfall (of ~ 1000 mm) over southwestern Taiwan. The Cloud-Resolving Storm Simulator with 1 km grid spacing was used to simulate the event, and it successfully reproduced the slow-moving rainbands, the embedded cells, and the dynamics of merger and back-building (BB) on 8 August as observed. Our model results suggest that the intense convection interacted strongly with the westerly LLJ that provided reversed vertical wind shear below and above the jet core. Inside mature cells, significant dynamical pressure perturbations (p'd) are induced with positive (negative) p'd at the western (eastern) flank of the updraft near the surface and a reversed pattern aloft (> 2 km). This configuration produced an upward-directed pressure gradient force (PGF) to the rear side and favors new development to the west, which further leads to cell merging as the mature cells slowdown in eastward propagation. The strong updrafts also acted to elevate the jet and enhance the local vertical wind shear at the rear flank. Additional analysis reveals that the upward PGF there is resulted mainly by the shearing effect but also by the extension of upward acceleration at low levels. In the horizontal, the upstream-directed PGF induced by the rear-side positive p'd near the surface is much smaller, but can provide additional convergence for BB development upstream. Finally, the cold-pool mechanism for BB appears to be not important in the Morakot case, as the conditions for strong evaporation in downdrafts do not exist.
Treatment options for vancomycin-resistant enterococci (VRE) bloodstream infection are limited. Studies comparing daptomycin or linezolid in treating VRE bloodstream infection have conflicting ...results and suggest daptomycin underdosing. The responses to different daptomycin doses have not been studied. We conducted a multicentre prospective cohort study to compare linezolid and daptomycin (≥6 mg/kg) for the treatment of VRE bloodstream infection. The primary outcome was 14-day mortality. We used multivariate logistic regression analysis for outcome analysis and a generalized additive model for dose-dependent response estimation. Two hundred twelve patients were included (daptomycin, n = 141; linezolid, n = 71). All-cause 14-day mortality was higher in the daptomycin group (36.9% vs. 21.1%; p 0.03). After adjusting for confounders in logistic regression, mortality was lower in the linezolid group (adjusted odds ratio (aOR), 0.45; 95% confidence interval (CI), 0.21–0.96; p 0.04). The generalized additive model showed that higher-dose daptomycin (≥9 mg/kg) was associated with better survival than lower-dose daptomycin (6–9 mg/kg). Logistic regression showed that linezolid (aOR, 0.36; 95% CI, 0.17–0.79; p 0.01) and higher-dose daptomycin (aOR, 0.26; 95% CI, 0.09–0.74; p 0.01) independently predicted lower mortality compared to lower-dose daptomycin. Linezolid was not superior to higher-dose daptomycin in terms of mortality (aOR, 1.40; 95% CI, 0.45–4.37; p 0.57). Higher-dose daptomycin had lower mortality than lower-dose daptomycin. Despite higher mortality for lower-dose daptomycin than linezolid, linezolid conferred no survival benefit compared to higher-dose daptomycin. Our findings suggest that the recommended daptomycin dose is suboptimal for treating VRE bacteraemia.
Accurate and robust pathological image analysis for colorectal cancer (CRC) diagnosis is time-consuming and knowledge-intensive, but is essential for CRC patients' treatment. The current heavy ...workload of pathologists in clinics/hospitals may easily lead to unconscious misdiagnosis of CRC based on daily image analyses.
Based on a state-of-the-art transfer-learned deep convolutional neural network in artificial intelligence (AI), we proposed a novel patch aggregation strategy for clinic CRC diagnosis using weakly labeled pathological whole-slide image (WSI) patches. This approach was trained and validated using an unprecedented and enormously large number of 170,099 patches, > 14,680 WSIs, from > 9631 subjects that covered diverse and representative clinical cases from multi-independent-sources across China, the USA, and Germany.
Our innovative AI tool consistently and nearly perfectly agreed with (average Kappa statistic 0.896) and even often better than most of the experienced expert pathologists when tested in diagnosing CRC WSIs from multicenters. The average area under the receiver operating characteristics curve (AUC) of AI was greater than that of the pathologists (0.988 vs 0.970) and achieved the best performance among the application of other AI methods to CRC diagnosis. Our AI-generated heatmap highlights the image regions of cancer tissue/cells.
This first-ever generalizable AI system can handle large amounts of WSIs consistently and robustly without potential bias due to fatigue commonly experienced by clinical pathologists. It will drastically alleviate the heavy clinical burden of daily pathology diagnosis and improve the treatment for CRC patients. This tool is generalizable to other cancer diagnosis based on image recognition.
Fragile histidine triad (FHIT) loss by the two-hit mechanism of loss of heterozygosity and promoter hypermethylation commonly occurrs in non-small cell lung cancer (NSCLC) and may confer cisplatin ...resistance in NSCLC cells. However, the underlying mechanisms of FHIT loss in cisplatin resistance and the response to cisplatin-based chemotherapy in NSCLC patients have not yet been reported. In the present study, inhibition concentration of 50% cell viability induced by cisplatin (IC50) and soft agar growth and invasion capability were increased and decreased in FHIT-knockdown and -overexpressing cells, respectively. Mechanistically, Slug transcription is upregulated by AKT/NF-κB activation due to FHIT loss and, in turn, Slug suppresses PUMA expression; this decrease of PUMA by FHIT loss is responsible for cisplatin resistance. In addition, cisplatin resistance due to FHIT loss can be conquered by AKT inhibitor-perifosine in xenograft tumors. Among NSCLC patients, low FHIT, high p-AKT, high Slug and low PUMA were correlated with shorter overall survival, relapse-free survival and poorer response to cisplatin-based chemotherapy. Therefore, the AKT inhibitor perifosine might potentially overcome the resistance to cisplatin-based chemotherapy in NSCLC patients with low-FHIT tumors, and consequently improve the outcome.
Summary
Background Bullous pemphigoid (BP) has been associated with neurological and psychiatric diseases; however, large‐scale population‐based study of different comorbid diseases in patients with ...BP is quite limited.
Objectives We sought to analyse the prevalence of neurological, psychiatric, autoimmune and inflammatory skin diseases prior to the diagnosis of BP and their associations with BP among patients with BP from a nationwide database in Taiwan.
Methods A total of 3485 patients with BP and 17 425 matching controls were identified from the National Health Insurance Database in Taiwan from 1997 to 2008. Conditional logistic regression analyses for a nested case–control study were performed to examine the prevalence of comorbidities prior to the diagnosis of BP between these two groups.
Results Overall, our results showed that stroke odds ratio (OR) 3·30; 95% confidence interval (95% CI) 3·03–3·60, dementia (OR 4·81; 95% CI 4·26–5·42), Parkinson disease (OR 3·49; 95% CI 3·05–3·98), epilepsy (OR 3·97; 95% CI 3·28–4·81), schizophrenia (OR 2·56; 95% CI 1·52–4·30) and psoriasis (OR 2·02; 95% CI 1·54–2·66) were significantly associated with BP. Among them, the association with schizophrenia and psoriasis was predominant in female and male patients, respectively, with BP. It remains for all these comorbid diseases to be independently associated with BP by multivariate analysis.
Conclusions Patients with BP are more likely to have various neurological diseases, schizophrenia and psoriasis prior to the diagnosis of BP, supporting associations found in other studies. Further research is required to elucidate the tentative causal association with BP.
Summary
Background
Inherited epidermodysplasia verruciformis (EV) is a rare skin disorder characterized by susceptibility to specific types of human papilloma virus (HPV) and is strongly associated ...with skin carcinomas. Inactivating mutations in EVER1/EVER2 account for most cases of EV. However, more phenotypes related to but distinct from EV have been reported with an immunodeficiency state but without EVER1/EVER2 mutation, and the genetic basis for these atypical EV cases is poorly understood.
Objectives
To identify the causative gene responsible for three siblings affected by atypical EV but without EVER1/EVER2 mutation.
Methods
Whole‐exome sequencing followed by Sanger sequencing was performed to identify the gene responsible for the patients with atypical EV enrolled in our study.
Results
A homozygous splicing mutation was detected in LCK (c.188‐2A>G). This mutation resulted in an exon 3 deletion T lymphocyte‐specific protein tyrosine kinase isoform, which further led to frameshift mutation and subsequent mRNA decay.
Conclusions
We demonstrate a novel mutation in LCK in a family affected by atypical EV with T‐cell defects, HPV infection and virus‐induced malignancy, providing new clues in the understanding of host defences against HPV and better genetic counselling of patients with the EV phenotype.
What's already known about this topic?
Epidermodysplasia verruciformis (EV) is an unusual genodermatosis characterized by an increased susceptibility to β‐human papillomavirus and is associated with a high risk of skin carcinoma.
Inactivating mutations in EVER1/EVER2 account for most cases of EV.
What does this study add?
Our study suggests an association between a novel splicing mutation in LCK and EV susceptibility.
What is the translational message?
Patients with EV should be tested for T lymphocyte‐specific protein tyrosine kinase deficiency and T‐cell function, which will help guide treatment.
Linked Comment: Uitto and Vahidnezhad. Br J Dermatol 2016; 175:1138–1139.
To evaluate the efficacy of stent placement in the treatment of portal vein (PV) stenosis or occlusion in living donor liver transplant (LDLT) recipients, 468 LDLT records were reviewed. Sixteen (10 ...PV occlusions and 6 stenoses) recipients (age range, 8 months–59 years) were referred for possible interventional angioplasty (dilatation and/or stent) procedures. Stent placement was attempted in all. The approaches used were percutaneous transhepatic (n = 10), percutaneous transsplenic (n = 4), and intraoperative (n = 2). Technical success was achieved in 11 of 16 patients (68.8%). The sizes of the stents used varied from 7 mm to 10 mm in diameter. In the five unsuccessful patients, long‐term complete occlusion of the PV with cavernous transformation precluded catherterization. The mean follow‐up was 12 months (range, 3–24). The PV stent patency rate was 90.9% (10/11). Rethrombosis and occlusion of the stent and PV occurred in a single recipient who had a cryoperserved vascular graft to reconstruct the PV during the LDLT operation. PV occlusion of >1 year with cavernous transformation seemed to be a factor causing technical failure. In conclusion, early treatment of PV stenosis and occlusion by stenting is an effective treatment in LDLT. Percutaneous transhepatic and transsplenic, and intraoperative techniques are effective approaches depending on the situation.
Vascular stents in management of portal venous complications: percutaneous transhepatic and transplenic and intraoperative techniques can be effective in patients with portal venous complications, depending on the situation.
Nanometer-thick passive films on metals usually impart remarkable resistance to general corrosion but are susceptible to localized attack in certain aggressive media, leading to material failure with ...pronounced adverse economic and safety consequences. Over the past decades, several classic theories have been proposed and accepted, based on hypotheses and theoretical models, and oftentimes, not sufficiently nor directly corroborated by experimental evidence. Here we show experimental results on the structure of the passive film formed on a FeCr
Ni
single crystal in chloride-free and chloride-containing media. We use aberration-corrected transmission electron microscopy to directly capture the chloride ion accumulation at the metal/film interface, lattice expansion on the metal side, undulations at the interface, and structural inhomogeneity on the film side, most of which had previously been rejected by existing models. This work unmasks, at the atomic scale, the mechanism of chloride-induced passivity breakdown that is known to occur in various metallic materials.
Anthropogenic atmospheric emissions of typical toxic heavy metals have caused worldwide concern due to their adverse effects on human health and the ecosystem. By determining the best available ...representation of time-varying emission factors with S-shape curves, we establish the multiyear comprehensive atmospheric emission inventories of 12 typical toxic heavy metals (Hg, As, Se, Pb, Cd, Cr, Ni, Sb, Mn, Co, Cu, and Zn) from primary anthropogenic activities in China for the period of 1949-2012 for the first time. Further, we allocate the annual emissions of these heavy metals in 2010 at a high spatial resolution of 0.5 degree 0.5 degree grid with ArcGIS methodology and surrogate indexes, such as regional population and gross domestic product (GDP). Our results show that the historical emissions of Hg, As, Se, Cd, Cr, Ni, Sb, Mn, Co, Cu, and Zn, during the period of 1949-2012, increased by about 22-128 times at an annual average growth rate of 5.1-8.0 %, reaching about 526.9-22 319.6 t in 2012. Nonferrous metal smelting, coal combustion of industrial boilers, brake and tyre wear, and ferrous metal smelting represent the dominant sources of heavy metal emissions. In terms of spatial variation, the majority of emissions are concentrated in relatively developed regions, especially for the northern, eastern, and southern coastal regions. In addition, because of the flourishing nonferrous metal smelting industry, several southwestern and central-southern provinces play a prominent role in some specific toxic heavy metals emissions, like Hg in Guizhou and As in Yunnan. Finally, integrated countermeasures are proposed to minimize the final toxic heavy metals discharge on account of the current and future demand of energy-saving and pollution reduction in China.
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