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Background: Definitive chemoradiation therapy (dCRT) is the standard treatment for patients with nonsurgical esophageal squamous cell carcinoma (ESCC), yet patients have demonstrated great variations in their responses to dCRT and inevitably progressed following treatment. Methods: To identify prognostic biomarkers, we performed targeted next‐generation sequencing of 416 cancer‐related genes on primary tumors from 47 nonsurgical ESCC patients prior to dCRT treatment. The association between genetic alterations and patients' local recurrence‐free survival (LRFS), progression‐free survival (PFS), and overall survival (OS) was analyzed. Results: TP53 (78% of patients), NOTCH1 (32%), ARID1A (13%), FAT1 (13%), and CDKN2A (13%) were commonly mutated in ESCC patients, while gene amplifications frequently occurred in MCL1 (36%), FGF19 (34%), MYC (32%), CCND1 (27%), ZNF217 (15%), CDKN2A (13%), and YAP1 (11%). Univariate and multivariate analyses of clinical factors and genetic alterations indicated that sex is an independent prognostic factor, with males tending to have better LRFS (hazard ratio [HR], 0.25; 95%CI, 0.08‐0.77, P =.015) and progression‐free survival (PFS) (HR, 0.35; 95%CI, 0.13‐0.93, P =.030) following dCRT. Meanwhile, YAP1 amplification (n = 7) was an adverse prognostic factor, and patients with this alteration demonstrated a tendency toward worse outcomes with shorter LRFS (HR, 4.06; 95%CI, 1.26‐13.14, P =.019) and OS (HR, 2.78; 95%CI, 0.95‐8.17, P =.062). In a subgroup analysis, while sex and M‐stage were controlled, a much stronger negative effect of YAP1 amplification vs wild‐type in LRFS was observed (log‐rank P =.0067). Conclusion: The results suggested that YAP1 amplification is a potentially useful biomarker for predicting treatment outcomes and identifying patients with a high risk of relapse who should be closely monitored. [ABSTRACT FROM AUTHOR]

The diagnosis of railway system faults is significant for its comfort, efficiency, and safety. The rail surface wear is the key impact factor when considering the health conditions of rails. This paper accomplishes contactless rail wear diagnosis by using multidimensional scaling based on a novel informational dissimilarity measure (IDM) to cluster intact and different worn rail profile data. The IDM uses weighted‐probability distribution of dispersion patterns to extract accurate time domain features from rail profile data, and the loss of information is minimized, which can greatly improve the accuracy for wear diagnosis. All the analyzing data for real experiments are collected by a laser scanner camera on an inspection car, where heavy‐haul railway rails with different types of surface wear are inspected. Experimental results with simulated and reality‐based data show that the proposed methods can identify worn profile data and discriminate different types of worn profiles more effectively when compared with existing methods. Thus, the proposed method offers a new thinking for the diagnosis of rail surface wear for heavy‐haul railways. [ABSTRACT FROM AUTHOR]

Familial multiple intestinal atresias is an autosomal recessive disease with or without combined immunodeficiency. In the last year, several reports have described mutations in the gene TTC7A as causal to the disease in different populations. However, exact correlation between different genotypes and various phenotypes are not clear. In this study, we report identification of novel compound heterozygous mutations in TTC7A gene in a Malay girl with familial multiple intestinal atresias and severe combined immunodeficiency ( MIA-SCID) by whole exome sequencing. We found two mutations in TTC7A: one that destroyed a putative splicing acceptor at the junction of intron 17/exon 18 and one that introduced a stop codon that would truncate the last two amino acids of the encoded protein. Reviewing the recent reports on TTC7A mutations reveals correlation between the position and nature of the mutations with patient survival and clinical manifestations. Examination of public databases also suggests carrier status for healthy individuals, making a case for population screening on this gene, especially in populations with suspected frequent founder mutations. [ABSTRACT FROM AUTHOR]

The controllable formation of zinc oxide ( ZnO) nanostructures and nanowires by a cheap and environmental friendly fabrication method of simply subjecting metallic zinc films in sodium chloride ( NaCl) solution at 170°C from 3 to 15 h under hydrothermal conditions is demonstrated in this study. Scanning electron microscopy ( SEM) and X-ray diffraction ( XRD) indicate that ZnO films with different morphologies are obtained: from a film with network of circular pores to a film with nanowire-like network with bigger pores. It is observed that heating duration has an effect on its photoluminescence ( PL) properties. Ultraviolet emission is observed for all ZnO films. Green emission surfaces after heating for 6 h, which subsequently disappears after 15 h of heating. It is suggested that the morphology change over different heating durations is responsible for the rise and subsequent decline in green emissions. Lastly, the growth mechanism behind zinc oxidation and morphology change is proposed and investigated with the aid of experimental method. It is verified that pitting corrosion is responsible for the growth mechanism here. [ABSTRACT FROM AUTHOR]

This paper proposes a hybrid approach to determine the fracture resistance for mode I and mixed-mode I and II fracture specimens, combining both numerically computed and experimentally measured load ( P) versus load-line displacement (LLD or Δ) relationships for metallic fracture specimens. The hybrid approach predicates on the same principle as the conventional, multiple-specimen experimental method in determining the energy release rate. The hybrid method computes the P-Δ curves from multiple finite element (FE) models, each with a different crack depth. The experimental procedure measures the P-Δ curve from a standard fracture specimen with a growing crack. The intersections between the experimental P-Δ curve and the numerical P-Δ curves from multiple FE models dictate the LLD levels to compute the strain energy ( U) using the area under the numerical P-Δ curves. This method provides accurate estimates of the J resistance data for both SE(B) specimen under mode I loading and single-edge notched specimens under mixed-mode I and II loading. [ABSTRACT FROM AUTHOR]

Background and Purpose: The cannabinoid CB(1) receptor is primarily thought to be functionally coupled to the G(i) form of G proteins, through which it negatively regulates cAMP accumulation. Here, we investigated the dual coupling properties of CB(1) receptors and characterized the structural determinants that mediate selective coupling to G(s) and G(i).Experimental Approach: A cAMP-response element reporter gene system was employed to quantitatively analyze cAMP change. CB(1)/CB(2) receptor chimeras and site-directed mutagenesis combined with functional assays and computer modelling were used to determine the structural determinants mediating selective coupling to G(s) and G(i).Key Results: CB(1) receptors could couple to both G(s)-mediated cAMP accumulation and G(i)-induced activation of ERK1/2 and Ca(2+) mobilization, whereas CB(2) receptors selectively coupled to G(i) and inhibited cAMP production. Using CB(1)/CB(2) chimeric receptors, the second intracellular loop (ICL2) of the CB(1) receptor was identified as primarily responsible for mediating G(s) and G(i) coupling specificity. Furthermore, mutation of Leu-222 in ICL2 to either Ala or Pro switched G protein coupling from G(s) to G(i), while to Ile or Val led to balanced coupling of the mutant receptor with G(s) and G(i) .Conclusions and Implications: The ICL2 of CB(1) receptors and in particular Leu-222, which resides within a highly conserved DRY(X)(5) PL motif, played a critical role in G(s) and G(i) protein coupling and specificity. Our studies provide new insight into the mechanisms governing the coupling of CB(1) receptors to G proteins and cannabinoid-induced tolerance. [ABSTRACT FROM AUTHOR]

Electrically induced fatigue crack growth is an important degradation mechanism for ferroelectric devices. Reliability concerns for ferroelectric devices place stringent demands for ferroelectric materials. In situ observation of electrically induced fatigue crack growth was carried out for ferroelectric single crystals under alternating electric field. Electrically induced fatigue crack growth was observed both below and above the coercive field. Crack closure and open behavior were observed together with 90° ferroelectric domain switching during the electric cycling. The crack propagation behavior is a repeated process of continuous but small increments followed by a sudden increase in the crack length. It was suggested that the electric boundary condition along the crack face, from its mouth to its tip, is a variation from the impermeable to the permeable state. The gradual attainment of an impermeable crack tip after an incubation period of field cycling causes the observed jump in crack propagation. [ABSTRACT FROM AUTHOR]

ABSTRACT Cracks often initiate from the mechanical joints which are widely used in structural components. It has been reported that cracks in mechanical joints are under mixed-mode condition and there is a critical angle at which mode I stress intensity factor becomes maximum. The crack propagates in an arbitrary direction and the prediction of fatigue crack growth path is needed to provide against crack propagation and examine safety. In this study, mixed-mode fatigue crack growth tests are performed for horizontal and critical inclined cracks in mechanical joints. Fatigue crack growth paths are predicted using a weight function approach and maximum tangential stress criterion. [ABSTRACT FROM AUTHOR]

To explode ultrasonographic pregnatal diagnosing value through retrospective study on absent pulmonary valve syndrome (APVS). 66558 examinations cases within 10 years from our centre were retrospectively studied by fetal echocardiography (FECG) include two dimension and Doppler imaging. APVS is typical shown by FECG include 2D and spectral Doppler and colour Doppler imaging, but isolate absent of pulmonary valve should be examed carefully to determine and exclude the other intracardiac malformations. [Extracted from the article]

In‐DRAM processing circuit is able to reduce operation time and power consumption than the traditional CPU + MEMORY system in performing the complicated computation such as convolution. These benefits are gained by bitwise and parallel processing of the in‐DRAM convolution circuit. To realise the in‐DRAM circuit, an inter‐bank processing circuit is proposed with bitwise summation/comparison circuit for performing convolution inside DRAM. Compared to the intra‐bank bitwise operation, the inter‐bank circuit can significantly reduce the power consumption and the number of row activation cycles to accomplish convolution. For the number of cycles, the inter‐bank circuit takes only 65 cycles for calculating 16 × 16 feature map. On the contrary, the intra‐bank needs as many as 192 cycles. In terms of power consumption, the inter‐bank circuit consumes smaller power by 35% than the intra‐bank. In the proposed in‐DRAM processing circuit, no complicated multiplier and adder are needed in performing the convolution. The Modified National Institute of Standards and Technology (MNIST) recognition rate of the proposed bitwise processing circuit can be as high as 97.28%, indicating very little loss due to the ternary kernels. [ABSTRACT FROM AUTHOR]

Objectives: Pancreatic cancer (PC) is one of the most lethal malignancies with an increasing death rate over the years. We performed targeted sequencing and survival analyses on 90 Chinese pancreatic cancer patients, hoping to identify genomic biomarkers associated with clinical outcomes and therapeutic options. Method: Genomic DNA was extracted from formalin‐fixed paraffin‐embedded (FFPE) tissue specimens of 90 pancreatic cancer patients and sequenced. The associations with clinicopathological factors were analyzed. Result: High prevalence of driver mutations in KRAS, TP53, CDKN2A, SMAD4, and ARID1A genes were found. Most mutated genes in PC belonged to cell cycle and DNA damage repair pathways. Tumors that arise from the pancreas' body and tail (BT tumors) displayed a higher ratio of mutated KRAS and TP53 than those that arise from the pancreas' head and neck (HN tumors), who showed less diverse KRAS subtypes. Patients with a KRAS p.G12R mutated tumor tended to have a prolonged disease‐free survival (DFS) and overall survival (OS) than other KRAS subtypes. Those with an altered ARID1A gene and more than two mutated driver genes tended to have a shorter DFS and OS. Conclusion: HN and BT tumors of the pancreas displayed different mutational profiles, which had prognostic significances and indicated different potential therapeutic options. [ABSTRACT FROM AUTHOR]

Association of circulating tumor DNA from the cerebrospinal fluid with high-risk CNS involvement in patients with diffuse large B-cell lymphoma Dear Editor, Central nervous system (CNS) involvement in diffuse large B-cell lymphoma (DLBCL) patients correlates with dismal outcomes, and the detection sensitivity of conventional diagnosis of lymphoma is restricted.1-4 Circulating tumor DNA from cerebrospinal fluid (CSF-ctDNA) has played an important part in the application of liquid biopsy for patients with CNS cancers.5 In this study, we provided new insights into feasibility of CSF-derived biomarkers for CNS relapse diagnosis in DLBCL patients. Moreover, we compared alterations in five CSF-CNS genes from systemic tumor tissue of DLBCL patients in high-risk (HR) group with an additional dataset of 40 patients clinically diagnosed as low risk (LR) for CNS relapse. Five CSF-CNS genes in CSF was found to be associated with CNS risk in DLBCL patients, which deserve further investigation to determine their relevance among the diagnosis, treatment, and outcome. [Extracted from the article]

An abstract of the article "The relevance study for fetal genetic soft marker, structural malformation and chromosomal abnormalities," by Q. Wu and W. Yang is presented.

ABSTRACT The fracture process of brittle materials with randomly orientated microcracks critically depends on strong interactions among microcracks and the coalescence path that leads to a fatal crack. In this paper, a model based on the coalescence process for planar orientated microcracks is presented. An energy ratio is defined as the competition between the potential energy release and the new crack surface energy in each coalescence step, which is a token of the excessive driving force for microcrack propagation. A critical linkage dictates the coalescence of microcracks under stress loading. Probabilities of microcrack coalescence dominated by the first linkage and subsequent linkages are analysed for collinear and wavy microcrack arrays in detail. [ABSTRACT FROM AUTHOR]

Polychromatic X-ray microdiffraction is an emerging tool for studying mesoscale structure and dynamics. Crystalline phase, orientation (texture), elastic and plastic strain can be nondestructively mapped in three dimensions with good spatial and angular resolution. Local crystallographic orientation can be determined to ∼0.01° and elastic strain tensor elements can be measured with a resolution of ∼10-4 or better. Complete strain tensor information can be obtained by augmenting polychromatic microdiffraction with a monochromatic measurement of one Laue-reflection energy. With differential-aperture depth profiling, volumes tens to hundreds of micrometers below the surface are accessible so that three-dimensional distributions of crystalline morphology including grain boundaries, triple points, second phases and inclusions can all be mapped. Volume elements below 0.25 μm³ are routinely resolved so that the grain boundary structure of most materials can be characterized. Here the theory, instrumentation and application of polychromatic microdiffraction are described. [ABSTRACT FROM AUTHOR]

Several recent studies have linked human chromosome 1p to essential hypertension (EH) or blood pressure (BP) levels. In an independent population of 148 hypertensive families from China we tested these findings. Thirty highly informative microsatellite markers spanning about 284 cM were genotyped. Qualitative linkage analysis was conducted using non-parametric linkage analysis implemented within the GENEHUNTER 2.0 software, whereas quantitative analysis was performed with the variance-component method integrated in the S.O.L.A.R. 1.7.4. software with an additional Haseman-Elston method using the SAGE/SIBPAL2 program. We observed suggestive linkage between D1S2890 (1p31, 80.9 cM) and hypertension using the multipoint non-parametric linkage analysis (NPL= 2.19, P= 0.01). In the quantitative analysis we didn't observe a significant excess of identity-by-descent allele sharing between the systolic blood pressure levels and the markers. However, the D1S207 microsatellite marker (1p21) which is located about 107 cM from the telomere of 1p showed weak linkage evidence with the diastolic blood pressure levels (LOD= 1.42). These findings suggest linkage of 1p31 with essential hypertension in the ethnic Chinese, and provide a potential clue for future studies involving candidate genes for hypertension. [ABSTRACT FROM AUTHOR]

Background: ALK‐tyrosine kinase inhibitors (TKIs) have been proven effective for treating ALK‐positive non‐small cell lung cancer (NSCLC), although patients present with variable responses and disease progression courses. The detailed underlying molecular mechanisms require further investigation to yield a better prognosis. Methods: Targeted next‐generation sequencing (NGS) mutation profiling was performed on samples from 42 NSCLC patients confirmed positive for ALK rearrangements by fluorescence in situ hybridization or immunohistochemistry who experienced disease progression after crizotinib treatment. Results: ALK rearrangements were not confirmed in six patients (14%) with other potential oncogenic drivers identified by NGS, who therefore did not respond to crizotinib and had significantly shorter overall survival (OS) compared to NGS ALK ‐positive patients. Fifteen ALK activating mutations were detected in 8 out of 26 post‐treatment samples (31%), among which ALK L1196M and G1269A were the most common acquired mutations detected in half of the patients with ALK activating mutations. Dynamic monitoring of the genetic evolution in one patient revealed both spatial and temporal heterogeneity of resistant mechanisms during different ALK‐TKI treatment courses. Activation of ALK downstream or bypass pathways was detected in patients without ALK activating mutations, such as genetic alterations in PIK3CA, MET, and KRAS. Interestingly, we identified two patients with acquired mutations in the DNA mismatch repair gene POLE, which resulted in a dramatically increased tumor mutation burden, and might contribute to the poor response to crizotinib. Conclusions: Heterogeneous resistant mechanisms have been identified and correlate to diverse responses to crizotinib. Comprehensive and dynamic mutation profiling is required to better predict clinical outcomes. [ABSTRACT FROM AUTHOR]

In-DRAM processing circuit is able to reduce operation time and power consumption than the traditional CPU + MEMORY system in performing the complicated computation such as convolution. These benefits are gained by bitwise and parallel processing of the in-DRAM convolution circuit. To realise the in-DRAM circuit, an inter-bank processing circuit is proposed with bitwise summation/ comparison circuit for performing convolution inside DRAM. Compared to the intra-bank bitwise operation, the inter-bank circuit can significantly reduce the power consumption and the number of row activation cycles to accomplish convolution. For the number of cycles, the inter-bank circuit takes only 65 cycles for calculating 16 × 16 feature map. On the contrary, the intra-bank needs as many as 192 cycles. In terms of power consumption, the inter-bank circuit consumes smaller power by 35% than the intra-bank. In the proposed in-DRAM processing circuit, no complicated multiplier and adder are needed in performing the convolution. The Modified National Institute of Standards and Technology (MNIST) recognition rate of the proposed bitwise processing circuit can be as high as 97.28%, indicating very little loss due to the ternary kernels. [ABSTRACT FROM AUTHOR]

Summary: Background: Fibrosis‐4 index (FIB‐4) is a surrogate marker for hepatic fibrosis in hepatitis B virus (HBV) carriers. Aim: To investigate whether FIB‐4 index stratifies the risks of adverse liver events. Methods: A total of 2075 treatment‐naïve, noncirrhotic the patients with chronic HBV infection were included. Most of them (82.1%) were HBeAg‐negative patients and their baseline FIB‐4 levels were explored to stratify the risks of cirrhosis, cirrhosis‐related complications and liver‐related mortality. Results: During a mean follow‐up period of 15.47 years, we found a higher baseline FIB‐4 index was associated with increased incidence rates of cirrhosis in addition to the common host and viral factors. Patients with FIB‐4 >1.29, compared to those with FIB‐4 <1.29, were associated with increased risks of cirrhosis, cirrhosis‐related complications and liver‐related mortality with the hazard ratio (95% confidence interval) of 6.19 (4.76‐8.05), 6.88, (3.68‐12.86) and 7.79, (4.54‐13.37) respectively. Within the first 3 years of follow‐up, FIB‐4 remained stable and its kinetics were consistently associated with the develoopment of adverse liver events. Furthermore, FIB‐4 index of 1.29 was able to stratify all the risks of adverse liver events even in HBeAg‐negative patients with a low risk of disease progression (HBV DNA <2000 IU/mL, HBsAg <1000 IU/mL and ALT <40 U/L). Only 1 patient with FIB‐4 index <1.29 developed cirrhosis but not other events within 15 years of follow‐up. Conclusions: In noncirrhotic patients with chronic HBV infection, a higher FIB‐4 index was associated with increased risks of adverse liver events. FIB‐4 index <1.29 is useful for the prediction of the lowest risks of disease progression. [ABSTRACT FROM AUTHOR]

Water sustainability in megacities is a growing challenge with far-reaching effects. Addressing sustainability requires an integrated, multidisciplinary approach able to capture interactions among hydrology, population growth, and socioeconomic factors and to reflect changes due to climate variability and land use. We developed a new systems modeling framework to quantify the influence of changes in land use, crop growth, and urbanization on groundwater storage for Beijing, China. This framework was then used to understand and quantify causes of observed decreases in groundwater storage from 1993 to 2006, revealing that the expansion of Beijing's urban areas at the expense of croplands has enhanced recharge while reducing water lost to evapotranspiration, partially ameliorating groundwater declines. The results demonstrate the efficacy of such a systems approach to quantify the impacts of changes in climate and land use on water sustainability for megacities, while providing a quantitative framework to improve mitigation and adaptation strategies that can help address future water challenges. [ABSTRACT FROM AUTHOR]

Type 2 diabetes ( T2D) is characterized by insulin resistance and impaired insulin secretion. The present study aimed to identify the influence of insulin sensitivity on the genetic risk of impaired insulin secretion among a Chinese Han population. For 3229 controls and 1994 treatment-naïve T2D, single nucleotide polymorphisms ( SNPs) from 24 T2D-related genomic loci were genotyped and a genetic risk score ( GRS) was constructed. Results showed that GRS was associated with insulin secretion and disposition indices in both controls and treatment-naïve T2Ds. Upon stratifying the participants into tertiles by the Matsuda index, we observed an inhibitory relationship between the GRS and insulin secretion in low insulin sensitive but not in high insulin sensitive controls and treatment-naïve T2Ds. Moreover, low insulin sensitive individuals exhibited more severe impairment in insulin secretion and beta cell response to insulin sensitivity with an increase in risk alleles. Our findings identified that the association of GRS with insulin secretion was strongly modulated by insulin sensitivity in both controls and T2Ds of Chinese Han. It indicates that insulin sensitization should be emphasized in prevention and treatment of T2D for beta cell protection. [ABSTRACT FROM AUTHOR]

Background Clearance of hepatitis B surface antigen ( HBsAg) indicates clinical control of hepatitis B virus ( HBV) infection. However, little is known about the impact of viral genomic variations on HBsAg loss. Methods We explored the association between viral genomic factors and HBsAg loss in 2121 HBeAg-negative patients. HBV pre-core stop codon (1896) and basal core promoter (BCP) (1762/1764) sequences were determined in patients with HBV DNA ≥200 IU/ mL ( N = 1693). The effect of HBV genotype on HBsAg loss was further validated in the whole cohort of 3445 HBsAg carriers. Results The cumulative lifetime (age 28-75 years) incidence of HBsAg loss was 50.4% in 2121 HBeAg-negative patients. We found that genotype C, but not pre-core stop codon or BCP mutants, was associated with HBsAg loss. Compared to genotype B patients, genotype C patients had higher lifetime chance of HBsAg loss, with hazard ratio of 1.8 (95% confidence interval: 1.4-2.4). Multivariable analysis showed that male sex, elevated ALT levels, lower serum HBV DNA and HBsAg levels, and genotype C infection were associated with higher chance of HBsAg loss independently. We then performed sensitivity analysis, which re-included HBeAg-positive, cirrhotic and treatment-experienced patients, and confirmed the robustness of our results in 3445 HBsAg carriers. Conclusion Genotype C infection, compared to genotype B, is associated with a higher lifetime chance of HBsAg loss in Asian HBV carriers. [ABSTRACT FROM AUTHOR]

Objective Progressive β-cell dysfunction hinders the maintenance of glycaemic control in type 2 diabetes, but comparative data on β-cell-protective therapies are lacking in the early stage of type 2 diabetes. Here we evaluated the comparative glycaemic efficacy and impact on β-cell function of three antihyperglycaemic agents that have a β-cell-protective effect, exenatide, insulin and pioglitazone, in newly diagnosed patients with type 2 diabetes. Design and methods In this 48-week, multicentre, parallel-group study, 416 patients newly diagnosed with type 2 diabetes were randomly assigned 1 : 1 : 1 to receive exenatide, insulin or pioglitazone. The primary end-point was the change in glycosylated haemoglobin (HbA1c) from baseline. Secondary end-points included effects on weight, blood pressure, lipid profiles and β-cell function assessed by homeostasis model assessment, fasting proinsulin:insulin ( PI/I), disposition index ( DI) and acute insulin response ( AIR). Results At week 48, mean [95% confidence interval ( CI)] HbA1c changes from baseline were −1.8% (−1.55% to −2.05%) with exenatide, −1.7% (−1.52% to −1.96%) with insulin and −1.5% (−1.23% to −1.71%) with pioglitazone. Treatment differences were −0.20% (95% CI −0.46% to 0.06%) for exenatide versus insulin ( P = 0.185), and −0.37% (95% CI −0.63% to −0.12%) for exenatide versus pioglitazone ( P = 0.002). Significant improvements from baseline in AIR, PI/I and DI were observed with all treatments, with the greatest improvements in DI, as well as weight, blood pressure and lipid profile, observed with exenatide. Conclusions All three agents showed efficacy regarding glycaemic control and metabolic benefits; however, exenatide showed the greatest efficacy. β-cell function improved in all treatment groups; hence, early initiation of β-cell-protective therapy may halt the decline in β-cell function in type 2 diabetes. [ABSTRACT FROM AUTHOR]

OBJECTIVE: Progressive [beta]-cell dysfunction hinders the maintenance of glycaemic control in type 2 diabetes, but comparative data on [beta]-cell-protective therapies are lacking in the early stage of type 2 diabetes. Here we evaluated the comparative glycaemic efficacy and impact on [beta]-cell function of three antihyperglycaemic agents that have a [beta]-cell-protective effect, exenatide, insulin and pioglitazone, in newly diagnosed patients with type 2 diabetes. DESIGN AND METHODS: In this 48-week, multicentre, parallel-group study, 416 patients newly diagnosed with type 2 diabetes were randomly assigned 1 : 1 : 1 to receive exenatide, insulin or pioglitazone. The primary end-point was the change in glycosylated haemoglobin (HbA1c) from baseline. Secondary end-points included effects on weight, blood pressure, lipid profiles and [beta]-cell function assessed by homeostasis model assessment, fasting proinsulin:insulin (PI/I), disposition index (DI) and acute insulin response (AIR). RESULTS: At week 48, mean [95% confidence interval (CI)] HbA1c changes from baseline were -1.8% (-1.55% to -2.05%) with exenatide, -1.7% (-1.52% to -1.96%) with insulin and -1.5% (-1.23% to -1.71%) with pioglitazone. Treatment differences were -0.20% (95% CI -0.46% to 0.06%) for exenatide versus insulin (P = 0.185), and -0.37% (95% CI -0.63% to -0.12%) for exenatide versus pioglitazone (P = 0.002). Significant improvements from baseline in AIR, PI/I and DI were observed with all treatments, with the greatest improvements in DI, as well as weight, blood pressure and lipid profile, observed with exenatide. CONCLUSIONS: All three agents showed efficacy regarding glycaemic control and metabolic benefits; however, exenatide showed the greatest efficacy. [beta]-cell function improved in all treatment groups; hence, early initiation of [beta]-cell-protective therapy may halt the decline in [beta]-cell function in type 2 diabetes. [ABSTRACT FROM AUTHOR]

The performance of multi-source multi-relay wireless networks based on a joint source-relay-selection scheme is investigated over Rayleigh interference-limited fading channels. The tight lower bound and asymptotic expressions for the outage probability are derived and the diversity order of the system with/without co-channel interference is further discussed. Simulation results are presented to demonstrate the validity of the theoretical analysis. [ABSTRACT FROM AUTHOR]

The performance of multi‐source multi‐relay wireless networks based on a joint source‐relay‐selection scheme is investigated over Rayleigh interference‐limited fading channels. The tight lower bound and asymptotic expressions for the outage probability are derived and the diversity order of the system with/without co‐channel interference is further discussed. Simulation results are presented to demonstrate the validity of the theoretical analysis. [ABSTRACT FROM AUTHOR]

Chromosome 6p is one of the most commonly implicated regions in the genome-wide linkage scans of schizophrenia, whereas further association studies for markers in this region were inconsistent likely due to heterogeneity. This study aimed to identify more homogeneous subgroups of families for fine mapping on regions around markers D6S296 and D6S309 (both in 6p24.3) as well as D6S274 (in 6p22.3) by means of similarity in neurocognitive functioning. A total of 160 families of patients with schizophrenia comprising at least two affected siblings who had data for eight neurocognitive test variables of the continuous performance test (CPT) and the Wisconsin card sorting test (WCST) were subjected to cluster analysis with data visualization using the test scores of both affected siblings. Family clusters derived were then used separately in family-based association tests for 64 single nucleotide polymorphisms (SNPs) covering the region of 6p24.3 and 6p22.3. Three clusters were derived from the family-based clustering, with deficit cluster 1 representing deficit on the CPT, deficit cluster 2 representing deficit on both the CPT and the WCST, and a third cluster of nondeficit. After adjustment using false discovery rate for multiple testing, SNP rs13873 and haplotype rs1225934-rs13873 on BMP6-TXNDC5 genes were significantly associated with schizophrenia for the deficit cluster 1 but not for the deficit cluster 2 or nondeficit cluster. Our results provide further evidence that the BMP6-TXNDC5 locus on 6p24.3 may play a role in the selective impairments on sustained attention of schizophrenia. [ABSTRACT FROM AUTHOR]

A letter to the editor on a study that reveals higher percentage of Chinese family with late-onset autosomal dominant non-syndromic progressive sensorineural hearing loss is presented.

We report here the clinical, genetic, and molecular characteristics of a large Chinese family exhibiting non-syndromic, late-onset autosomal dominant sensorineural hearing loss. Clinical evaluation revealed variable phenotypes of hearing loss in terms of severity and age-at-onset of disease in these subjects. Genome-wide linkage analysis mapped the disease gene to the DFNA5 locus with a maximum two-point log odds score of 5.39 at [theta] = 0 for marker D7S2457. DNA sequencing of DFNA5 revealed a novel heterozygous IVS8+4 A>G substitution in the splice donor site of intron 8. Reverse transcriptase–polymerase chain reaction (RT–PCR) showed skipping of exon 8 in the mutant transcript. This mutation faithfully cosegregated with hearing loss in the family. In addition, the mutation was absent in 100 unrelated control DNA samples of Chinese origin. The IVS8+4 A>G mutation is predicted to create a shift in the reading frame and introduce a stop codon at position 372, thereby resulting in a prematurely truncated DFNA5 protein. Up to date, a total of four mutations in DFNA5 have been reported to lead to hearing impairment, all of them result in skipping of exon 8 at the mRNA level. Our findings provide further support for the hypothesis that DFNA5-associated hearing loss is caused by a very specific gain-of-function mutation. [ABSTRACT FROM AUTHOR]

Evidence for association with schizophrenia has been reported for NOTCH4, although results have been inconsistent. Previous studies have focused on polymorphisms in the 5′ promoter region and first exon of NOTCH4. Our aim was to test the association of the entire genomic region of NOTCH4 in 218 families with at least two siblings affected by schizophrenia in Taiwan. We genotyped seven single nucleotide polymorphisms (SNPs) of this gene, with average intermarker distances of 5.3 kb. Intermarker linkage disequilibrium (LD) was calculated usinggold software, and single-locus and haplotype association analyses were performed usingtransmit software. We found that the T allele of SNP rs2071285 ( P= 0.035) and the G allele of SNP rs204993 ( P= 0.0097) were significantly preferentially transmitted to the affected individuals in the single-locus association analysis. The two SNPs were in high LD (D′ > 0.8). Trend for overtransmission was shown for the T-G haplotype of the two SNPs to affected individuals ( P= 0.053), with the A-A haplotype significantly undertransmitted ( P= 0.034). The associated region distributed across the distal portion of the NOTCH4 gene and overlapped with the genomic region of the G-protein signaling modulator 3 and pre-B-cell leukemia transcription factor 2. In summary, we found modest association evidence between schizophrenia and the distal genomic region of NOTCH4 in this Taiwanese family sample. Further replication for association with the distal genomic region of NOTCH4 is warranted. [ABSTRACT FROM AUTHOR]

To explore the detection rate, types, accompanying abnormalities and prognosis of fetal congenital heart disease (CHD) in a single centre of northwest China, in order to lay a foundation for further studying the epidemiological characteristics of fetal CHD and integrated management of FCHD in the prenatal and postnatal. The number of abortion cases, intrauterine and postnatal natural deaths of fetal CHD accounted for 60.3% (1357/2251) of the total follow-up, of which complex CHD and chromosomal abnormalities accounting for the majority. The fetal complex CHD were more common while the prognosis were worse than simple CHD, but some types of complex CHD could be corrected by surgery by pregnancy monitoring and evaluation. [Extracted from the article]

Background: One of the major challenges in managing invasive breast cancer (BC) is the lack of reliable biomarkers to track response. Circulating tumor DNA (ctDNA) from liquid biopsy, as a candidate biomarker, provides a valuable assessment of BC patients. In this retrospective study, we evaluated the utility of ctDNA to reflect the efficacy of treatment and to monitor resistance mechanisms. Methods: Targeted next‐generation sequencing (NGS) of 416 cancer‐relevant genes was performed on 41 plasma biopsy samples of 19 HER2+ and 12 HER2‐ BC patients. Longitudinal ctDNA samples were analyzed in three BC patients over the treatment course for detecting acquired mutations. Results: In HER2+ BC patients, ERBB2 somatic copy numbers in ctDNA samples were significantly higher in patients progressed on HER2‐targeted therapy than those who were still responding to the treatment. Recurrent acquired mutations were detected in genes including ERBB2, TP53, EGFR, NF1, and SETD2, which may contribute to trastuzumab resistance. In longitudinal analyses, the observed mutation allele frequencies were tracked closely in concordance with treatment responses. A novel ERBB2 p.(Leu869Arg) mutation was acquired in one patient upon resistant to trastuzumab therapy, which was further validated as an oncogenic mutation in vitro and contributed to resistance. In HER2‐ BC patients with chemotherapy resistance, genetic alterations on TP53, PIK3CA, and DNA damage repair genes were frequently observed. Conclusions: In summary, ctDNA monitoring, particularly longitudinal analyses, provides valuable insights into the assessment of targeted therapy efficacy and gene alterations underlying trastuzumab resistance and chemotherapy resistance in HER2+ and HER2‐ BC patients, respectively. [ABSTRACT FROM AUTHOR]

A capacitive-type MEMS acoustic sensor with a planarised TiN/plasma-enhanced chemical vapour deposition-Si3N4/TiN diaphragm based on a polyimide sacrificial layer is presented. The multi-layer diaphragm has the effective residual stress of +31.5 MPa. Furthermore, this sensor features a 21% lower parasitic capacitance and a 56% lower air-gap resistance in comparison with those of a sensor fabricated without planarisation. Five photomasks were used. In addition, to evaluate the frequency response, both an effective capacitance model and an equivalent circuit model equipped with a voltage-controlled voltage source are newly proposed and compared with conventional models. The open-circuit sensitivity is modelled to -45.4 dBV/Pa at 1 kHz with 9.6 V, indicating a difference of 0.9 dB in comparison with the open-circuit sensitivity of the conventional model. [ABSTRACT FROM AUTHOR]

An abstract of the article "Retrospective study of fetal echocardiography and follow-up after birth in a single centre," by Y. Wang and colleagues is presented.