Organic Intercalation Induced Kinetic Enhancement of Vanadium Oxide Cathodes for Ultrahigh-Loading Aqueous Zinc-Ion Batteries.
Vanadium-based oxides have attracted much attention because of their rich valences and adjustable structures. The high theoretical specific capacity contributed by the two-electron-transfer process (V5+ /V3+ ) makes it an ideal cathode material for aqueous zinc-ion batteries. However, slow diffusion kinetics and poor structural stability limit the application of vanadium-based oxides. Herein, a strategy for intercalating organic matter between vanadium-based oxide layers is proposed to attain high rate performance and long cycling life. The V3 O7 ·H2 O is synthesized in situ on the carbon cloth to form an open porous structure, which provides sufficient contact areas with electrolyte and facilitates zinc ion transport. On the molecular level, the added organic matter p-aminophenol (pAP) not only plays a supporting role in the V3 O7 ·H2 O layer, but also shows a regulatory effect on the V5+ /V4+ redox process due to the reducing functional group on pAP. The novel composite electrode with porous structure exhibits outstanding reversible specific capacity (386.7 mAh g-1 , 0.1 A g-1 ) at a high load of 6.5 mg cm-2 , and superior capacity retention of 80% at 3 A g-1 for 2100 cycles.


GLUT1 and GLUT8 in endometrium and endometrial adenocarcinoma.
Glucose is provided to cells by a family of glucose transport facilitators known as GLUTs. These transporters are expressed in a tissue specific manner and are overexpressed in many primary tumors of these tissues. Regulation of glucose transport facilitator expression has been demonstrated in endometrial tissue and endometrial adenocarcinoma. The following experiments were conducted to quantify and localize the expression of GLUT1 and GLUT8 in benign endometrium and compare this expression to endometrial cancer. Endometrial tissue samples were obtained from random hysterectomy specimens of patients with benign indications for surgery and endometrial cancer. Immunoblot and immunolocatization studies were performed using GLUT1 and GLUT8 specific antisera. Endometrial samples from 65 women who had undergone hysterectomy were examined (n=38 benign, n=27 malignant). A 44 and a 35.4 kDa immunoreacive species was demonstrated in endometrium and endometrial cancer for GLUT1 and GLUT8, respectively. Upregulation of GLUT1 expression was demonstrated with increasing grade of tumors (P<0.002). GLUT8 expression was increased in all tumor subtypes compared to atrophic endometrium (P<0.001). Apical localization by GLUT1 and GLUT8 was demonstrated in endometrial glands. GLUT1 and GLUT8 demonstrated diffuse intracellular localization in the cancer subtypes. GLUT1 and GLUT8 are expressed in both human endometrium and endometrial cancer. There appears to be a step-wise progression in GLUT1 and GLUT8 expression as tumor histopathology worsens. GLUT1 and GLUT8 may be important markers in tumor differentiation, as well as providing energy to rapidly dividing tumor cells.


Dementia in the oldest old: a multi-factorial and growing public health issue.
The population of oldest old, or people aged 85 and older, is growing rapidly. A better understanding of dementia in this population is thus of increasing national and global importance. In this review, we describe the major epidemiological studies, prevalence, clinical presentation, neuropathological and imaging features, risk factors, and treatment of dementia in the oldest old. Prevalence estimates for dementia among those aged 85+ ranges from 18 to 38%. The most common clinical syndromes are Alzheimer's dementia, vascular dementia, and mixed dementia from multiple etiologies. The rate of progression appears to be slower than in the younger old. Single neuropathological entities such as Alzheimer's dementia and Lewy body pathology appear to have declining relevance to cognitive decline, while mixed pathology with Alzheimer's disease, vascular disease (especially cortical microinfarcts), and hippocampal sclerosis appear to have increasing relevance. Neuroimaging data are sparse. Risk factors for dementia in the oldest old include a low level of education, poor mid-life general health, low level of physical activity, depression, and delirium, whereas apolipoprotein E genotype, late-life hypertension, hyperlipidemia, and elevated peripheral inflammatory markers appear to have less relevance. Treatment approaches require further study, but the oldest old may be more prone to negative side effects compared with younger patients and targeted therapies may be less efficacious since single pathologies are less frequent. We also highlight the limitations and challenges of research in this area, including the difficulty of defining functional decline, a necessary component for a dementia diagnosis, the lack of normative neuropsychological data, and other shortcomings inherent in existing diagnostic criteria. In summary, our understanding of dementia in the oldest old has advanced dramatically in recent years, but more research is needed, particularly among varied racial, ethnic, and socioeconomic groups, and with respect to biomarkers such as neuroimaging, modifiable risk factors, and therapy.


[The effect of amplitude-frequency characteristics of the noise-covered test stimulus on the form of visual evoked potentials].
Visual evoked potentials in response to reverse checkerboard patterns presented in additive noise were analyzed. An induced by noise changes in visual evoked potentials form and in amplitude-frequency spectrum of checkerboard patterns were compared. It was found that character of visual evoked potentials form alteration correlated with stimulus amplitude-frequency spectrum alterations. Results obtained here support Gestalt-psychology view about using by visual system a spatial-frequency but not a discrete information description.


Effect of rituximab in patients with PLA2R-associated membranous nephropathy and malignancy.
Phospholipase A2 receptor (PLA2R)-associated membranous nephropathy (MN) is a common cause of nephrotic syndrome in nondiabetic adults who are also within the common age group for malignancy. How to treat patients with PLA2R-associated MN and malignancy effectively and safely still requires careful consideration. The aim of our study was to examine the outcomes and safety of rituximab (RTX) in these patients. Retrospective analysis of clinical data was performed on 15 patients with PLA2R-associated MN and malignancy. Patients were followed every 1-3 months for a minimum of 24 months. Clinical data were collected, including CD19+ B cells, anti-PLA2R antibodies, 24-hour urinary protein, serum albumin, and serum creatinine. The percentage of patients who achieved clinical remission and immunological remission was also measured. Among these 15 patients, 14 patients with solid tumors received treatment for malignant diseases with complete resection. One patient received chemotherapy for chronic myeloid leukemia, and achieved complete remission 36 months before the diagnosis of MN. There were 6 (40.00 %) patients who achieved complete remission and 14 (93.33 %) patients who achieved complete or partial remission at the last visit after RTX treatment. At the last visit, patients were clinically improved, as evidenced by significant improvements in anti-PLA2R antibody titer [2.00 (2.00, 2.00) vs 35.25 (11.18, 91.58) RU/ml, P = 0.002], 24-hour urine protein [0.39 (0.11, 2.28) vs 9.22 (4.47, 14.73) g/d, P = 0.001], and serum albumin [38.15 (34.80, 43.20) vs 23.70 (18.70, 25.70) g/L, P = 0.001]. During the follow-up, the renal function of those patients remained stable. Recurrence of malignant tumors or the occurrence of new tumor events were not observed. In this single-center retrospective study with a small sample size, RTX therapy might be an effective and safe treatment in patients with PLA2R-associated MN and malignancy.


Improved Quantitative Plant Proteomics via the Combination of Targeted and Untargeted Data Acquisition.
Quantitative proteomics strategies - which are playing important roles in the expanding field of plant molecular systems biology - are traditionally designated as either hypothesis driven or non-hypothesis driven. Many of these strategies aim to select individual peptide ions for tandem mass spectrometry (MS/MS), and to do this mixed hypothesis driven and non-hypothesis driven approaches are theoretically simple to implement. In-depth investigations into the efficacies of such approaches have, however, yet to be described. In this study, using combined samples of unlabeled and metabolically 15N-labeled Arabidopsis thaliana proteins, we investigate the mixed use of targeted data acquisition (TDA) and data dependent acquisition (DDA) - referred to as TDA/DDA - to facilitate both hypothesis driven and non-hypothesis driven quantitative data collection in individual LC-MS/MS experiments. To investigate TDA/DDA for hypothesis driven data collection, 7 miRNA target proteins of differing size and abundance were targeted using inclusion lists comprised of 1558 m/z values, using 3 different TDA/DDA experimental designs. In samples in which targeted peptide ions were of particularly low abundance (i.e., predominantly only marginally above mass analyser detection limits), TDA/DDA produced statistically significant increases in the number of targeted peptides identified (230 ± 8 versus 80 ± 3 for DDA; p = 1.1 × 10-3) and quantified (35 ± 3 versus 21 ± 2 for DDA; p = 0.038) per experiment relative to the use of DDA only. These expected improvements in hypothesis driven data collection were observed alongside unexpected improvements in non-hypothesis driven data collection. Untargeted peptide ions with m/z values matching those in inclusion lists were repeatedly identified and quantified across technical replicate TDA/DDA experiments, resulting in significant increases in the percentages of proteins repeatedly quantified in TDA/DDA experiments only relative to DDA experiments only (33.0 ± 2.6% versus 8.0 ± 2.7%, respectively; p = 0.011). These results were observed together with uncompromised broad-scale MS/MS data collection in TDA/DDA experiments relative to DDA experiments. Using our observations we provide guidelines for TDA/DDA method design for quantitative plant proteomics studies, and suggest that TDA/DDA is a broadly underutilized proteomics data acquisition strategy.


Variables related to the quality of life of families that have a child with severe to profound intellectual disabilities: A systematic review.
Family quality of life (FQoL) of families that have a child with severe to profound intellectual disabilities (SPID) is an important and emerging concept, however, related variables are inconclusive. To gain a better understanding of variables related to the FQoL of families that have a child with SPID, variables related to the FQoL of families that have a child with intellectual disabilities (ID) were systematically reviewed. A search strategy was performed in five databases. Critical appraisal tools were employed to evaluate the quality of both quantitative and qualitative studies. Data extraction and synthesis occurred to establish general study characteristics, variables, and theoretical concepts. Variables were categorised into four key concepts of the FQoL: systemic concepts, performance concepts, family-unit concepts and individual-member concepts. A total of 40 studies were retrieved with 98 variables. Quality scores ranged from 7 to 13 (quantitative) and 5 to 13 (qualitative) out of 13 and 14 points, respectively. Five out of the 40 studies (13%) focused on individuals with SPID. Variables related positively or negatively to the FQoL, and were categorised within systemic concepts (n = 3); performance concepts (n = 11); family-unit concepts (n = 26); and individual-member concepts (n = 58). Several variables were found to be (inter)related to the FQoL of families that have a child with ID. A contrasting picture emerged regarding the impact of a disability in relation to transitional phases. However, studies which include families of children with SPID were minimal, therefore, it remained ambiguous to what extent the identified variables apply to these families.


Magnetic skyrmions in FePt nanoparticles having Reuleaux 3D geometry: a micromagnetic simulation study.
The magnetization reversal in magnetic FePt nanoelements having Reuleaux 3D geometry is studied using micromagnetic simulations employing Finite Element discretizations. Magnetic skyrmions are revealed in different systems generated by the variation of the magnitude of the magnetocrystalline anisotropy which was kept normal to the nanoelement's base and parallel to the applied external field. The topological quantity of skyrmion number is computed in order to characterize micromagnetic configurations exhibiting skyrmionic formations. Micromagnetic configurations with a wide range of skyrmion numbers between -3 and 3 are indicative for the existence of one or multiple skyrmions that have been detected and stabilized in a range of external fields. Internal magnetic structures are shown consisting of Bloch type skyrmionic entities in the bulk altered to Néel skyrmions on the nanoelement's bottom and top base surfaces. The actual sizes of the formed skyrmions and the internal magnetization structures were computed. In particular, the sizes of the generated and persistent skyrmions were calculated as functions of the magnetocrystalline anisotropy value and of the applied external magnetic field. It is shown that the size of skyrmions is linearly dependent on the external field value. The slope of the linear curve can be controlled by the magnetocrystalline anisotropy value. The magnetic skyrmions can be created for FePt magnetic systems lacking of chiral interactions by designing the geometry-shape of the nanoparticle and by controlling the value of magnetocrystalline anisotropy.


Nevoid basal-cell carcinoma syndrome.
The nevoid basal-cell carcinoma syndrome is characterized by major manifestations, such as multiple basal-cell carcinomata, cysts of the jaws, and skeletal--specifically, rib--abnormalities. Findings in 53 patients and a review of the literature document both major and lesser-known manifestations of the disorder. The odontogenic keratocyst, which usually appears during adolescence, has a marked tendency to recur. In addition to the skin tumors, milia, epidermoid cysts, chalazia, comedones, and palmar and plantar pits are frequent. The skin tumors, originally thought to be independent of sun exposure, are more common in sun-exposed areas and are far less frequent and occur at a much later age in blacks than in whites. There is some evidence that radiation of the skin promotes the appearance of skin cancers in this disorder. Unilateral linear nevoid basal-cell carcinomas with comedones may represent postzygotic somatic mutation. A proclivity to other forms of neoplasia exists. Patients with this syndrome have had medulloblastoma, meningioma, ovarian fibroma, ovarian fibrosarcoma, fibrosarcoma of the jaws, cardiac fibroma, fetal rhabdomyoma, and lymphatic or chylous cysts of the mesentery. In addition to the usual modalities of treatment, topical immunotherapy and topical 5-fluorouracil have been used with success. Oral synthetic retinoids, such as 13-cis-retinoic acid, have been used to prevent new lesions from appearing and to arrest the growth of older lesions by inducing differentiation. The independent observations of increased prostaglandin levels associated both with odontogenic keratocyst expansion and aggression of basal cell cancers merit further investigation both as a fundamental cellular mechanism and as a possible basis for treatment (e.g., with antiprostaglandins). The key to pre- and early postnatal diagnosis of the disorder--as well as to an understanding of the basic abnormality--lies in molecular genetics. Prime attention should be given to finding the site of the gene through the use of DNA and other markers.


Unsupervised deep learning reveals prognostically relevant subtypes of glioblastoma.
One approach to improving the personalized treatment of cancer is to understand the cellular signaling transduction pathways that cause cancer at the level of the individual patient. In this study, we used unsupervised deep learning to learn the hierarchical structure within cancer gene expression data. Deep learning is a group of machine learning algorithms that use multiple layers of hidden units to capture hierarchically related, alternative representations of the input data. We hypothesize that this hierarchical structure learned by deep learning will be related to the cellular signaling system. Robust deep learning model selection identified a network architecture that is biologically plausible. Our model selection results indicated that the 1st hidden layer of our deep learning model should contain about 1300 hidden units to most effectively capture the covariance structure of the input data. This agrees with the estimated number of human transcription factors, which is approximately 1400. This result lends support to our hypothesis that the 1st hidden layer of a deep learning model trained on gene expression data may represent signals related to transcription factor activation. Using the 3rd hidden layer representation of each tumor as learned by our unsupervised deep learning model, we performed consensus clustering on all tumor samples-leading to the discovery of clusters of glioblastoma multiforme with differential survival. One of these clusters contained all of the glioblastoma samples with G-CIMP, a known methylation phenotype driven by the IDH1 mutation and associated with favorable prognosis, suggesting that the hidden units in the 3rd hidden layer representations captured a methylation signal without explicitly using methylation data as input. We also found differentially expressed genes and well-known mutations (NF1, IDH1, EGFR) that were uniquely correlated with each of these clusters. Exploring these unique genes and mutations will allow us to further investigate the disease mechanisms underlying each of these clusters. In summary, we show that a deep learning model can be trained to represent biologically and clinically meaningful abstractions of cancer gene expression data. Understanding what additional relationships these hidden layer abstractions have with the cancer cellular signaling system could have a significant impact on the understanding and treatment of cancer.


[Intensive therapy in burns and carbon monoxide poisoning].
While treatment conduction of 38 patients with severe burns and poisoning with carbonic oxide in complex of antishock measures there was applied a nondirect electrochemical oxidation of blood and internal laser irradiation of blood. There was used He-Nd laser. The mortality lowering by 3.3 times in comparison with 40 patients, in whom the traditional intensive therapy was applied, was noted.


The Hybrid cochlear implant: a review.
The Hybrid S or 'short-electrode' cochlear implant was developed to treat patients with a severe to profound hearing loss limited to the high frequencies. The short electrode is implanted into just the base or high-frequency region of the cochlea, with the goal of preserving residual low-frequency hearing. As a result, electric stimulation can be combined with acoustic stimulation in the same ear (and the opposite ear); this is one instance of 'acoustic plus electric' (A + E) stimulation. In this paper, we will review the latest findings from the first two stages of the clinical trial for the Hybrid concept in the United States. Generally, we will review surgical techniques, clinical trial criteria, residual hearing preservation, improvements in speech perception in quiet, and predictive factors for patient benefit. We will also discuss the significant benefit of A + E stimulation for speech perception in noise and musical measures of melody and instrument recognition, as well as valuable insights into central auditory nervous system plasticity gained from the use of a very short electrode array.


[Functional state of the hepatocyte cytoplasmic network in heliotrine injury of the rat liver].
Effect of an alkaloid heliotrine (25 mg per 100 g of body mass) on the functional state of cytoplasmic net in rat hepatocytes was studied. Distinct prolongation of hexenale sleep, decrease in content of protein, cytochromes P-450 and b5 as well as inhibition of oxidative degradation of amidopyrine and aniline in liver microsomal fraction were found. The data obtained suggest that a decrease in the rate of xenobiotics biotransformation in hepatocytes is one of the factors responsible for intoxication of a body and for impairment in pharmacodynamics of the drugs metabolized in liver tissue under conditions of acute toxic hepatites.


Modelling age-friendly environment for social connectedness: a cross-sectional study.
Background: The increase in aged populations in Malaysia has brought unprecedented challenges to families, policy makers, scholars, and business organisations. This paper adapted the WHO 2007 framework of features of age-friendly cities to examine age-friendly environment constructs and their linkages with social connectedness from the perspective of Malaysian middle-aged and older adults caring for themselves. Methods: A face-to-face cross-sectional survey was conducted on 402 middle-aged and older adults caring for themselves across selected states in west Malaysia, selected via purposive sampling. Firstly, features of age-friendly cities were explored through exploratory factor analysis involving 82 respondents. Subsequently, structural equation modelling was performed, involving 320 respondents. Results: The results indicated that the constructs of an age-friendly environment were built environment, community support and health services, civic participation, and employment as well as communication and information. The structural model provided evidence that implementing age-friendly initiatives relating to built environment, community support and health services, civic participation and employment as well as communication and information enables the ageing population to improve their connectedness with society. These findings supported the ecological theories, agreeing that age-friendly environments help middle-aged and older adults caring for themselves to increase their adaptability and reduce perceived pressure from the environment. This result was in line with the current literature in which an age-friendly environment is a form of support and an enabling environment to cultivate positive social relationships and connectivity. Conclusions: Creating an age-friendly environment that supports active and healthy living for middle-aged and older adults caring for themselves allows them to continue to share their experiences, knowledge, and wisdom. This is helpful and beneficial for societal well-being and economic development as well as for the future generations.


Quantitation of alpha-factor internalization and response during the Saccharomyces cerevisiae cell cycle.
The alpha-factor pheromone binds to specific cell surface receptors on Saccharomyces cerevisiae a cells. The pheromone is then internalized, and cell surface receptors are down-regulated. At the same time, a signal is transmitted that causes changes in gene expression and cell cycle arrest. We show that the ability of cells to internalize alpha-factor is constant throughout the cell cycle, a cells are also able to respond to pheromone throughout the cycle even though there is cell cycle modulation of the expression of two pheromone-inducible genes, FUS1 and STE2. Both of these genes are expressed less efficiently near or just after the START point of the cell cycle in response to alpha-factor. For STE2, the basal level of expression is modulated in the same manner.


Comparison of effects of peripheral vasculature on tonometric radial pulse and cuff-based brachial pulse waveform as used in estimation of central aortic pressures.
Aortic pressure estimation requires reliable peripheral pulse waveform acquisition. The peripheral waveform can change with local vascular effects that can be independent of aortic pressure. This study quantifies the effects of peripheral vasculature changes on radial and brachial waveforms. In 20 subjects (37± 15 years, 7 female), brachial volumetric displacement (cuff-based) and radial tonometry waveforms were simultaneously measured whilst a cuff around the hand on the same arm was inflated to induce transmural pressures of -60, -30, -15, 0, 15 and 30 mmHg, altering local peripheral resistance and compliance by graded arterial wall unloading. Aortic blood pressure (BP), augmentation index (AIx) and ejection duration were calculated from the measurements using a generalized transfer function. The parameters under unloaded conditions were compared to baseline measurements. Brachial systolic and diastolic BP did not change throughout the experiment. Altering peripheral resistance and compliance did not significantly change calculated aortic BP values, although changes were nominally greater for radial (maximum +8±1 mmHg) compared to brachial (maximum +2±1 mmHg) waveforms. AIx at 0 mmHg transmural pressure (maximum arterial wall unloading) was higher when derived from radial waveforms (+24±3%, p<0.001) but not when derived from brachial waveforms. Localized changes in peripheral resistance and compliance affect tonometer acquired radial waveforms but not volumetric displacement acquired brachial pressure waveforms, as judged by computed central aortic augmentation pressure parameters. This suggests aortic pressure estimation from the brachial cuff waveform is less sensitive to peripheral vasculature disturbances that alter the peripheral arterial pulse morphology.


Relationship between patient-based descriptions of sinusitis and paranasal sinus computed tomographic findings.
To evaluate the relationship of paranasal sinus symptoms with coronal computed tomographic (CT) findings. Prospective comparison of patient-based symptoms with imaging findings. Primary care and referral center office and hospital practices. Of 586 consecutive patients referred by otolaryngologists and primary care physicians for CT of the paranasal sinuses, 221 (151 women and 70 men; age range, 13-82 years; mean age, 44 years) participated by completing the Sino-Nasal Outcome Test-20 (SNOT-20) clinical questionnaire immediately before undergoing CT. Radiologists blinded to the patients' responses scored the degree of mucosal thickening at each of 12 sites on CT scans using a staged scale of severity (0-2 points). Bivariate analysis was performed to assess the relationship between patients' symptoms and CT findings. The SNOT-20 scores ranged from 0 (normal) to 78 (mean, 34). The most commonly reported symptom was fatigue. The CT scores ranged from 0 (normal) to 24 (mean, 4.07). Seventy-five patients (34%) had normal findings on the CT scan. The maxillary sinus was the most commonly involved site (96 patients, or 43%). The SNOT-20 and CT scores failed to significantly correlate (r = 0.11, P < or = .09). When the subset of patients with "positive" or "very positive" CT scans were considered, no significant correlation was observed (r = 0.12, P < or = .16). For the 132 patients reporting facial pain, the mean CT score was lower than for patients without facial pain (3.78 vs 4.78, P = .21). Patient-based reports of paranasal sinus symptoms failed to correlate with findings on CT scans; therefore, CT should be reserved for delineating the anatomy and pattern of inflammatory paranasal disease prior to surgical intervention.


Mobilization of Ca2+ by cyclic ADP-ribose from the endoplasmic reticulum of cauliflower florets.
The NAD+ metabolite cADP-Rib (cADPR) elevates cytosolic free Ca2+ in plants and thereby plays a central role in signal transduction pathways evoked by the drought and stress hormone abscisic acid. cADPR is known to mobilize Ca2+ from the large vacuole of mature cells. To determine whether additional sites for cADPR-gated Ca2+ release reside in plant cells, microsomes from cauliflower (Brassica oleracea) inflorescences were subfractionated on sucrose density gradients, and the distribution of cADPR-elicited Ca2+ release was monitored. cADPR-gated Ca2+ release was detected in the heavy-density fractions associated with rough endoplasmic reticulum (ER). cADPR-dependent Ca2+ release co-migrated with two ER markers, calnexin and antimycin A-insensitive NADH-cytochrome c reductase activity. To investigate the possibility that contaminating plasma membrane in the ER-rich fractions was responsible for the observed release, plasma membrane vesicles were purified by aqueous two-phase partitioning, everted with Brij-58, and loaded with Ca2+: These vesicles failed to respond to cADPR. Ca2+ release evoked by cADPR at the ER was fully inhibited by ruthenium red and 8-NH2-cADPR, a specific antagonist of cADPR-gated Ca2+ release in animal cells. The presence of a Ca2+ release pathway activated by cADPR at higher plant ER reinforces the notion that, alongside the vacuole, the ER participates in Ca2+ signaling.


Abnormal glucose tolerance and lipid abnormalities in Indian myocardial infarct survivors.
Glucose tolerance and lipid levels in a random sample of 103 Indian patients (96 males and 7 females) with coronary artery disease (CAD) aged between 20 and 55 years were compared with those in a healthy Indian control group matched as regards age and sex. Previous episodes of myocardial infarction were taken as evidence of CAD. Of the patients 44% were overweight. Glucose tolerance was abnormal in 55% of the patients. Both cholesterol and triglyceride values in the patients with CAD were significantly higher than those in the control group. Serum cholesterol levels were over 6,5 mmol/l in 62% of the patients with CAD and serum triglyceride levels were over 2,0 mmol/l in .53%. Males with CAD tended to have lower plasma high-density lipoprotein (HDL) cholesterol levels than the control group (P less than 0,01). There was a significant negative correlation between body mass index and HDL cholesterol, and no correlation was demonstrated between body mass index and total cholesterol or triglyceride levels. Furthermore, when the patients were sub-grouped according to their glucose tolerances it was found that only the triglyceride levels were significantly different (values were higher in those with abnormal glucose tolerance). Our data suggest that abnormal glucose tolerance and lipid aberrations are significant risk factors in Indian patients with CAD.


Interobserver variation in the histopathological assessment of nonalcoholic steatohepatitis.
Pathological assessment is considered as the gold standard for the diagnosis of nonalcoholic steatohepatitis (NASH). However, there is no agreement of histological features required for the diagnosis of NASH. In the present study, eight experienced hepatopathologists read liver biopsy specimen slides of 21 cases of NASH and suspected NASH independently and were asked to assess histopathological features and render a diagnosis. Interobserver variation among pathologists was evaluated by kappa statistics. Significant, good agreement was present in evaluation of the extent of steatosis and grade of fibrosis. Agreement was moderate concerning the localization of steatosis, localization of fibrosis, and glycogen nuclei. Only slight or poor agreement was seen in evaluation of type of steatosis, ballooning, intralobular necroinflammatory change, portal inflammation, and degree of neutrophilic infiltration. Thus the agreement varied for histological variables. Significant, moderate agreement was seen in the diagnosis of NASH but agreement was poor in the diagnosis of suggestive NASH. The agreement for the diagnosis of NASH was not high as for the individual histological findings that were thought to be the basis of the diagnosis. In conclusion, some histological features in NASH might prove useful for the development of a standardized and reliable pathological diagnosis and scoring system.


In vitro investigation of the hepatobiliary disposition mechanisms of the antifungal agent micafungin in humans and rats.
The purpose of the present study was to elucidate the transport mechanisms responsible for elimination of micafungin, a new semisynthetic echinocandin antifungal agent, which is predominantly cleared by biliary excretion in humans and rats. In vitro studies using sandwich-cultured rat and human hepatocytes were conducted. Micafungin uptake occurred primarily (∼75%) by transporter-mediated mechanisms in rat and human. Micafungin uptake into hepatocytes was inhibited by taurocholate (K(i) = 61 μM), Na(+) depletion (45-55% reduced), and 10 μM rifampin (20-25% reduced); these observations support the involvement of Na(+)-taurocholate-cotransporting polypeptide (NTCP/Ntcp) and, to a lesser extent, organic anion-transporting polypeptides in the hepatic uptake of micafungin. The in vitro biliary clearance of micafungin, as measured by the B-CLEAR technique, amounted to 14 and 19 μl/(min · mg protein) in human and rat, respectively. In vitro biliary excretion of micafungin was reduced by 80 and 75% in the presence of the bile salt export pump (BSEP) inhibitors taurocholate (100 μM) and nefazodone (25 μM), respectively. Biliary excretion of micafungin also was reduced in the presence of breast cancer resistance protein inhibitors [N-(4-[2-(1,2,3,4-tetrahydro-6,7-dimethoxy-2-isoquinolinyl)ethyl]-phenyl)-9,10-dihydro-5-methoxy-9-oxo-4-acridine carboxamide (GF120918) (10 μM) and fumitremorgin C (10 μM)]. In vitro biliary excretion of micafungin was not significantly altered by coincubation with P-glycoprotein or multidrug resistance-associated protein 2 inhibitors. These results suggest that NTCP/Ntcp and BSEP/Bsep are primarily responsible for hepatobiliary disposition of micafungin in human and rat. Interference with hepatic bile acid disposition could be one mechanism underlying hepatotoxicity associated with micafungin in some patients.


Acrylic bone cements: influence of time and environment on physical properties.
Acrylic bone cements are in extensive use in joint replacement surgery. They are weight bearing and load transferring in the bone-cement-prosthesis complex and therefore, inter alia, their mechanical properties are deemed to be crucial for the overall outcome. In spite of adequate preclinical test results according to the current specifications (ISO, ASTM), cements with inferior clinical results have appeared on the market. The aim of this study was to investigate whether it is possible to predict the long term clinical performance of acrylic bone cement on the basis of mechanical in vitro testing. We performed in vitro quasistatic testing of cement after aging in different media and at different temperatures for up to 5 years. Dynamic creep testing and testing of retrieved cement were also performed. Testing under dry conditions, as required in current standards, always gave higher values for mechanical properties than did storage and testing under more physiological conditions. We could demonstrate a continuous increase in mechanical properties when testing in air, while testing in water resulted in a slight decrease in mechanical properties after 1 week and then levelled out. Palacos bone cement showed a higher creep than CMW3G and the retrieved Boneloc specimens showed a higher creep than retrieved Palacos. The strength of a bone cement develops more slowly than the apparent high initial setting rate indicates and there are changes in mechanical properties over a period of five years. The effect of water absorption is important for the physical properties but the mechanical changes caused by physical aging are still present after immersion in water. The established standards are in need of more clinically relevant test methods and their associated requirements need better definition. We recommend that testing of bone cements should be performed after extended aging under simulated physiological conditions. Simple quasistatic and dynamic creep tests seem unable to predict clinical performance of acrylic bone cements when the products under test are chemically very similar. However, such testing might be clinically relevant if the cements exhibit substantial differences.


Reappraisal of the 1990 American College of Rheumatology criteria for the classification of cutaneous vasculitis: an analysis based on 766 patients.
The term cutaneous vasculitis (CV) includes a wide and heterogeneous group of entities. The American College of Rheumatology (ACR) established a set of criteria to classify vasculitis in 1990. Our aim was to further investigate into the applicability of these criteria for the classification of patients with primary CV. We analysed a large and unselected series of patients with CV attended to a university referral centre from January 1976 to December 2011. Patients were classified according to the methodology and criteria proposed by the ACR1990 core data set. Patients were also classified according to the same ACR 1990 database as proposed by Michel et al. in 1992 to differentiate Henoch-Schönlein purpura (HSP) from hypersensitivity vasculitis (HV). We assessed 766 patients (346 women and 420 men) with a mean age of 34 years. Patients with cutaneous lesions in the setting of conditions different from primary CV were excluded. According to the 1990 ACR criteria, 405 (63.1%) of the 642 patients with primary CV were classified as having HSP and 230 (35.8%) as HV. However, 119 (18.5%) patients fulfilled the ACR 1990 criteria for both entities. In addition, 7 (1.1%) did not meet the ACR 1990 criteria for any of them and, therefore, they were considered as non-classified vasculitis. When patients with primary CV were tested for the Michel et al. criteria, 392 (61.1%) were classified as having HSP and 250 (38.9%) as HV. Frequent discordance between the ACR 1990 and the Michel et al. criteria was observed. It ranged between 18.4 and 21.7% for HSP and 32.2 to 38% for HV. According to our data, the ACR 1990 criteria are of limited value for the classification of patients with primary CV.


Early changes in system [Formula: see text] and glutathione in the retina of diabetic rats.
Diabetic retinopathy (DR), the main cause of blindness among diabetic patients, affects both neuronal and vascular cells of the retina. Studies show that neuronal cell death begins after 4 weeks of diabetes and could be related with an increase in oxidative stress. System [Formula: see text] is a glutamate/cystine exchanger, formed by a catalytic subunit called xCT and a regulatory subunit 4F2hc, whose activity is crucial to the synthesis of glutathione, which is a key antioxidant molecule for cells. Although some studies have shown that glutamate transport mediated by excitatory amino acid transporters (EAATs) in diabetic rats is downregulated, there are no studies investigating system [Formula: see text] in this context. To evaluate whether system [Formula: see text] is modified by early onset of diabetes, primary retinal cell culture exposed to high glucose and retinas of rats 3 weeks after streptozotocin injection were used. We observed that xCT subunit protein expression both in cultures and in vivo were diminished. Furthermore, system [Formula: see text] activity and GSH levels were also decreased whereas oxidative stress was increased in retinas of diabetic animals. Therefore, this study raises the possibility that alterations in system [Formula: see text] expression and activity could occur during early onset of diabetes. In that way, system [Formula: see text] modifications could be related to increased ROS in diabetic retinopathy.


Distribution, functional impact, and origin mechanisms of copy number variation in the barley genome.
There is growing evidence for the prevalence of copy number variation (CNV) and its role in phenotypic variation in many eukaryotic species. Here we use array comparative genomic hybridization to explore the extent of this type of structural variation in domesticated barley cultivars and wild barleys. A collection of 14 barley genotypes including eight cultivars and six wild barleys were used for comparative genomic hybridization. CNV affects 14.9% of all the sequences that were assessed. Higher levels of CNV diversity are present in the wild accessions relative to cultivated barley. CNVs are enriched near the ends of all chromosomes except 4H, which exhibits the lowest frequency of CNVs. CNV affects 9.5% of the coding sequences represented on the array and the genes affected by CNV are enriched for sequences annotated as disease-resistance proteins and protein kinases. Sequence-based comparisons of CNV between cultivars Barke and Morex provided evidence that DNA repair mechanisms of double-strand breaks via single-stranded annealing and synthesis-dependent strand annealing play an important role in the origin of CNV in barley. We present the first catalog of CNVs in a diploid Triticeae species, which opens the door for future genome diversity research in a tribe that comprises the economically important cereal species wheat, barley, and rye. Our findings constitute a valuable resource for the identification of CNV affecting genes of agronomic importance. We also identify potential mechanisms that can generate variation in copy number in plant genomes.


Intraspecific deception by bluffing: a defense strategy of newly molted stomatopods (arthropoda: crustacea).
After molting, stomatopods can be evicted easily from home cavities by conspecifics because these marine crustaceans lose temporarily their body armor and the use of their raptorial appendages. Some newly molted stomatopods defend their cavities with a meral spread display, a signal correlated with attack when used by animals between molts. The use of the meral spread display actually increases after molting. Since new molts cannot fight, their use of meral spread appears to be a bluff.


MARIAN: an analysis tool for the assessment of left ventricular function measured by velocity encoding MRI.
Velocity encoding MRI is a new non-invasive technique for measuring cardiac blood flow velocities. Flow in the three directions of space can be measured during the entire heart cycle. However, the analysis of large amount of data obtained from this technique requires specialized computational software packages to provide physicians with efficient analysis tools. A data visualization software package named Magnetic Resonance Imaging Analyzer (MARIAN) was developed. This software package uses visualization, animation, analysis, and computational tools adapted to time series of cardiac MRI data files, all accessible through a sophisticated graphics user interface. MARIAN was used as a tool for the analysis of the left heart blood flow patterns in two groups of human subjects: ten volunteers and eight patients. The patients were diagnosed with incapacitating angina pectoris and previous left ventricular myocardial infarction. Vector plot animations of the left atrial flow were realized for all volunteer examinations. The temporal flow velocity profiles were sampled at the tips of the mitral leaflets and in the lumen of the right upper pulmonary vein, when possible. The isovolumic relaxation time (IVRT) was estimated. The following flow parameters were obtained from the velocity profiles: at the mitral valve, the early diastolic E-wave, the late diastolic A-wave, the time of occurrence of the E- and A- waves; at the right upper pulmonary vein, the systolic S-wave, the early diastolic D-wave and the reverse late diastolic R-wave. The results obtained were consistent with previous studies using similar MRI techniques. Compared to the control group, the patient group exhibited higher isovolumic relaxation time, a lower peak E-wave, and a lower D-wave. MARIAN thus provided a fast, efficient and accurate data visualization tool for the analysis of human data.


Effect of different types of conditioning contraction on upper body postactivation potentiation.
Muscle contractions preceding an activity can result in increased force generation (postactivation potentiation [PAP]). Although the type of muscular contractions could affect subsequent strength and power performance, little information exists on their effects. The purpose of this study was to examine PAP effects produced by isometric (ISO), concentric (CON), eccentric (ECC), or concentric-eccentric (DYN) conditioning contractions on upper body force and power performance. Ten male, competitive rugby players (mean ± SD: age 20.4 ± 0.8 years, height 177.0 ± 8.1 cm, body mass 90.2 ± 13.8 kg) performed a ballistic bench press throw (BBPT) followed by a 10-minute rest and one of the conditioning contractions. After a 12-minute rest, the subjects performed another BBPT (post-BBPT). The conditioning contractions, applied on separate days and in counterbalanced randomized order, were a 7-second isometric barbell bench press for ISO and 1 set of 3 bench press repetitions at 3 repetition maximum for CON, ECC, and DYN (each repetition lasting 2 seconds for CON and ECC, overall execution time <7 seconds for DYN). Peak power (Ppeak), peak force (Fpeak), maximum distance (Dmax) and rate of force development (RFD) were measured using a linear position transducer. Electromyography (EMG) of the pectoralis major and triceps brachii was also recorded. The ISO produced significantly higher Ppeak (587 ± 116 and 605 ± 126 W for pre- and post-BBPT, respectively; p < 0.05). No significant differences in Ppeak were revealed for CON, ECC, and DYN (p > 0.05), and no significant differences existed in Fpeak, Dmax, and RFD for ISO, CON, ECC, and DYN (p > 0.05). Finally, EMG was not significantly different between pre- and post-BBPT for any of the conditioning contractions (p > 0.05). Isometric contractions appear to be the only conditioning contractions increasing upper body power output after long resting periods.


[Factors affecting smoking of elementary and high school children from Chile].
Despite the harmful effects of tobacco millions of people continue to smoke. Many of these smokers, including most news smokers, are adolescents-both in Chile and in other countries. This study sought to determine the prevalence of smoking among Chilean elementary and high school children and to quantify the relative impact of socioeconomic, socio-cultural, familial, mass media exposure, demographic, educational and psychosocial factors on smoking. A representative sample of 2,967 elementary and high school children from Chile's Metropolitan Region were chosen at random, by grade (IV, VI, and VIII elementary school grades and I and IV high school grades), sex, type of school and geographical area. Prevalence of smoking was determined through an anonymous self-administered questionnaire. Socioeconomic status (SES) was measured by means of Graffar's modified method and family conditions, mass media exposure and psychosocial factors were registered. Scholastic achievement was measured by a language and mathematics test and other educational variables were considered. Statistical procedures included analysis of variance. Student's test and Scheffe's test for comparison of means, correlation, stepwise multiple regression, chisquared and PAHO/WHO risk approach methodology. Prevalence of smoking (10.6%) increased significantly with age, from 1.3% in school children aged < 13 years to 15.4% and 36.9%, in adolescent students aged 13-15 years and > or = 16 years, respectively (p < 0.001) and was higher in females than in males. Pleasure level (r = 0.499 p < 0.001), level of rebelliousness (r = 0.124 p < 0.0001), family recreation level (r = -0.131 p < 0.0001) and the percentage of school attendance (r = -0.118 p < 0.0001) were the independent variables with the greatest explanatory power in smoking variance (r2 = 0.2860), but pleasure level was the variable with the greatest explanatory power in the explained variance (89.2%) and with the greatest RR (34.3). The relative impact of the independent variables on smoking varied according to age, sex and SES. The result demonstrate that pleasure level, level of rebelliousness, family recreation level and the percentage of school attendance were the independent variables with the greatest explanatory power in smoking. These findings may be useful in the implementation of education and health policies with a view to the reduction of this serious public health risk factor.


Effects of food allergy on the dietary habits and intake of primary schools' Cypriot children.
Aim. To determine whether food allergy affects overall dietary intake and food choices in Cypriot primary school children. Methods. As part of the first epidemiological study in Cyprus on food allergy in primary school children, two 24-hour recalls (one from a week and one from a weekend day) of twenty-eight food allergic children (21 girls) and thirty healthy children (20 girls) aged 6-11 years old, were analysed and compared regarding their macro- and micronutrient content, food choices and meal distribution. Results. Significant differences between the two subgroups of children were estimated regarding the total energy intake and macronutrients, where food allergic children were found to consume in lower quantities, as well as for calcium, niacin, fiber and vitamin E. Food allergic children were also found to avoid combining foods from the various food groups in their meals, and to prefer specific food products from each category, whereas they consumed higher amounts of sugar and fructose. Conclusion. Food allergy in Cypriot food allergic children impacts on both the quality and quantity of food choices, probably due to lack of nutritional education regarding proper elimination diet and alternative nutrient sources.


Phase II trial of PN401, 5-FU, and leucovorin in unresectable or metastatic adenocarcinoma of the stomach: a Southwest Oncology Group study.
From February, 2001 to September, 2002, the Southwest Oncology Group (SWOG) accrued 65 patients with advanced gastric adenocarcinoma to a phase II trial of weekly 5-FU, leucovorin, and the orally-administered uridine analog PN401. Of these 65 patients, 57 were assessable for survival and toxicity, which were the endpoints for the study. Treatment consisted of the administration of 1200 mg/m(2) of 5-FU, 500 mg/m(2) of leucovorin, and 6 grams of PN401 every 8 h, beginning 8 h after the completion of the 5-FU infusion, and continuing for a total of 8 doses (48 grams) during each weekly chemotherapy session. Therapy was delivered for six weeks out of every 8-week treatment cycle. The gastrointestinal toxicity of this regimen was mild with 2 patients experiencing grade 3 stomatitis, and 6 patients having grade 3 diarrhea; and the hematologic toxicity was acceptable with 6 of 57 patients found to have had grade 3 or 4 leukopenia, and 14 of 57 patients experiencing grade 3 or 4 neutropenia. There were two deaths judged possibly related to treatment; one in a patient who experienced a variety of Grade 2 gastrointestinal toxicities and died at home with an unknown cause of death; and a second patient who also died at home, and for whom treatment-related sepsis could not be ruled out. The overall median survival was 7.2 months. The ability to safely deliver twice the usual dose of 5-FU with leucovorin on a weekly schedule suggests that oral uridine analog supplementation with PN401 may enhance the therapeutic index of the fluoropyrimidines.


Evaluation of laser scanning confocal microscopy as a method for characterizing reef-building coral tissue thickness and Symbiodiniaceae fluorescence.
Predicting the sensitivity of reef-building corals to disturbance, including bleaching, requires an understanding of physiological responses to stressors, which may be limited by destructive sampling and the capacity of common methodologies to characterize early life history stages. We developed a new methodology using laser scanning confocal microscopy (LSCM) to measure and track the physiological condition of corals. In a thermal stress experiment, we used LSCM to track coral condition during bleaching in adults and juveniles of two species, Montipora capitata and Pocillopora acuta Depth of fluorescence in coral tissues provides a proxy measure of tissue thickness, whereas Symbiodiniaceae population fluorescence relates to both population density and chlorophyll a content. In response to thermal stress, there were significant shifts in tissue thickness and Symbiodiniaceae fluorescence with differences between life stages. This method is particularly well suited for detecting shifts in physiological condition of living corals in laboratory studies, especially in small juvenile colonies.


Specific replacements of pyruvate for trophic support of central and peripheral nervous system neurons.
When embryonic central nervous system neurons are seeded at low densities with Eagle's basal medium supplemented with the serum substitute N1, glucose, and glutamine, neuronal survival for even 24 h requires the additional supply of exogenous pyruvate--and so does the survival of many peripheral nervous system neurons. Pyruvate can be replaced by alpha-ketoglutarate or oxaloacetate, but not by Krebs cycle substrates that are not keto acids. Most other alpha-keto acids tested (though not beta- or gamma-keto acids) also mimic pyruvate. The apparent equivalence to pyruvate of all these compounds includes identical ED50 values (300 microM for embryonic avian fore-brain neurons, 30-40 microM for rat hippocampal neurons), and also identical susceptibilities to the pyruvate-sparing effects of other low-molecular-weight agents present in Dulbecco's modified Eagle's medium or in astroglia conditioned medium. The substitute alpha-keto acids, however--unlike pyruvate, alpha-ketoglutarate, or oxaloacetate--support cell survival only in the presence of alpha-amino acids that transaminate to alpha-ketoglutarate, oxaloacetate, or pyruvate. The alpha-keto acids, therefore, operate as acceptors of amino groups from appropriate donors to generate Krebs cycle-relevant substrates. Consistent with this view, [14C]glutamate did not generate appreciable 14CO2 unless accompanied by a suitable alpha-keto acid.(ABSTRACT TRUNCATED AT 250 WORDS)


Resilient Delayed Impulsive Control for Consensus of Multiagent Networks Subject to Malicious Agents.
Impulsive control is widely applied to achieve the consensus of multiagent networks (MANs). It is noticed that malicious agents may have adverse effects on the global behaviors, which, however, are not taken into account in the literature. In this study, a novel delayed impulsive control strategy based on sampled data is proposed to achieve the resilient consensus of MANs subject to malicious agents. It is worth pointing out that the proposed control strategy does not require any information on the number of malicious agents, which is usually required in the existing works on resilient consensus. Under appropriate control gains and sampling period, a necessary and sufficient graphic condition is derived to achieve the resilient consensus of the considered MAN. Finally, the effectiveness of the resilient delayed impulsive control is well demonstrated via simulation studies.


[The pharmacokinetics of Kefzol in patients with acute pancreatitis when administered intravenously and endolymphatically].
Pharmacokinetics was studied of kefsole administered by intravenous and endolymphatic routes to patients (n = 23) with acute pancreatitis. The studies made showed that intravenous route for the drug administration makes for a quicker entering of the antibiotic into the peritoneal exudate. Apart from these reasons, endolymphatic antibacterial therapy does not appear to avert the development of complications involving pus-formation/discharging in acute pancreatitis and does not seem to be essential in the complex of therapeutic measures to be applied for treating the above patients.


Colorimetric Indicators Based on Anthocyanin Polymer Composites: A Review.
This review explores the colorimetric indicators based on anthocyanin polymer composites fabricated in the last decade, in order to provide a comprehensive overview of their morphological and compositional characteristics and their efficacy in their various application fields. Notably, the structural properties of the developed materials and the effect on their performance will be thoroughly and critically discussed in order to highlight their important role. Finally, yet importantly, the current challenges and the future perspectives of the use of anthocyanins as components of colorimetric indicator platforms will be highlighted, in order to stimulate the exploration of new anthocyanin sources and the in-depth investigation of all the possibilities that they can offer. This can pave the way for the development of high-end materials and the expansion of their use to new application fields.


Angiogenic and invasive properties of neurofibroma Schwann cells.
Neurofibromas are benign tumors from patients with von Recklinghausen Neurofibromatosis (NF1) that are comprised primarily of Schwann cells. These Schwann cells are found both in association with axons and in the extracellular matrix that is prevalent in neurofibromas, and in which fibroblasts are also abundant. An unresolved question has been whether cells in neurofibromas are normal cells or are intrinsically abnormal. We have tested the hypothesis that cells in neurofibromas are abnormal and have shown that neurofibroma Schwann cells, unlike normal Schwann cells, promote angiogenesis in the chick chorioallantoic membrane model system, and invade basement membranes in this system. In contrast, neurofibroma fibroblasts neither promote angiogenic reactions nor invade basement membranes. When injected into nude mice, neurofibroma Schwann cells do not form progressive tumors. These results suggest that NF1 Schwann cells differ from normal Schwann cells, that they are preneoplastic, and that genetic and/or epigenetic changes in Schwann cells may be required for development of peripheral nerve tumors in NF1.


Comparing classification methods for longitudinal fMRI studies.
We compare 10 methods of classifying fMRI volumes by applying them to data from a longitudinal study of stroke recovery: adaptive Fisher's linear and quadratic discriminant; gaussian naive Bayes; support vector machines with linear, quadratic, and radial basis function (RBF) kernels; logistic regression; two novel methods based on pairs of restricted Boltzmann machines (RBM); and K-nearest neighbors. All methods were tested on three binary classification tasks, and their out-of-sample classification accuracies are compared. The relative performance of the methods varies considerably across subjects and classification tasks. The best overall performers were adaptive quadratic discriminant, support vector machines with RBF kernels, and generatively trained pairs of RBMs.


'Secretly, it's a competition': a qualitative study investigating what helped employees quit smoking during a workplace smoking cessation group training programme with incentives.
Smoking cessation programmes in combination with financial incentives have shown to increase quit rates in smokers, but it is not clear which elements of this intervention help smokers to succeed in their quit attempt. The aim of this study was to explore the view of successful and unsuccessful quitters about which factors had affected their ability to quit smoking. Semistructured qualitative interviews were conducted and analysed using the Framework method. Interviews were conducted in 2017 with employees from nine different Dutch companies. 24 successful and unsuccessful quitters from the intervention group of a cluster randomised controlled trial (RCT) who participated in a workplace smoking cessation group training programme in which smoking abstinence was rewarded with financial incentives. Themes that emerged were the workplace setting, quitting with colleagues, motivation, family support, strategies and the financial incentives. The interviewees reported that the smoking cessation programme was appreciated in general, was convenient, lowered the threshold to sign up, stimulated peer support and competition and provided strategies to resist smoking. Personal motivation and a mind set to never smoke again were regarded as important factors for quit success. The financial incentives were not considered as a main motivator to quit smoking, which contradicts the results from the RCT. The financial incentives were considered as more attractive to smokers with a low income. According to participants, contributors to quitting smoking were the workplace cessation programme, personal motivation and peer support, but not the incentives. More research is needed on the contradiction between the perceived effects of financial incentives on quit success and the actual difference in quit rates. NTR5657.


Use of Lipid-modifying Therapy and LDL-C Goal Attainment in a High-Cardiovascular-Risk Population in the Netherlands.
This study investigates lipid-modifying therapy (LMT) and LDL-C goal attainment in a real-world, high-cardiovascular-risk population in the Netherlands. From the PHARMO Database Network, patients aged ≥18 years with an LDL-C measurement in 2012 (index date) were selected and hierarchically classified into the following mutually exclusive high-cardiovascular-risk categories: familial hypercholesterolemia (FH), recent acute coronary syndrome (ACS), coronary heart disease, ischemic stroke, peripheral arterial disease, and diabetes mellitus. LMT use and LDL-C goal attainment at the index date was assessed. Of 61 839 patients who met the inclusion criteria, 1132 (2%) had FH, 2431 (4%) had recent ACS, 6292 (10%) had coronary heart disease, 2868 (5%) had ischemic stroke, 3017 (5%) had peripheral arterial disease, and 46 099 (75%) had diabetes mellitus. Overall, 67% of patients were receiving LMT. Use of LMT ranged from 77% for recent ACS to 53% for FH, and standard-potency statins were the most prescribed. The percentage attaining an LDL-C goal of <100 mg/dL was 55%, ranging from 23% (FH) to 58% (recent ACS). Among LMT users, 69% taking high-potency statins, 70% taking standard-potency statins, and 20% receiving nonstatin LMTs attained an LDL-C goal of <100 mg/dL. LMT use among high-cardiovascular-risk patients was modest, which contributed to 46% of the cohort failing to reach LDL-C goals <100 mg/dL. Underuse and suboptimal use of LMTs in this cohort represent opportunities for quality improvement programs aimed at reducing the risk of cardiovascular events.


A Flow Dynamic Rationale for Accelerated Vascularized Composite Allotransplant Rejection.
From 1996 to 2000, Diefenbeck et al. carried out six knee vascularized composite allotransplants. The allotransplants were composed of bone, soft tissue, and femoral vascular pedicle (25 to 40 cm). All rejected between 14 and 56 months. Failures were attributed to chronic rejection. In 2008, the Louisville team lost their fourth patient's hand transplant at 8 months. During the rejection workup, intraoperative findings noted a thickened arterial pedicle attributed to intimal hyperplasia with significant fibrotic perivascular tissue and a near "no-flow phenomenon." No cutaneous rejection was appreciated and failure was attributed to chronic rejection. Data were collected from two teams, one in Germany and the other in Louisville, Kentucky. The population under study consisted of the six knee and one hand transplants. The factor of interest was the long donor arterial pedicle. The outcome measurements were transplant survival time and histopathologic results. There are only seven published vascularized composite allotransplant cases where a donor artery longer than 25 cm was used. This cohort represents a 100 percent accelerated failure rate. The cause of these losses remains unexplained. The donor arteries suffered from T-cell-mediated rejection and ischemia-induced media/adventitial necrosis. We hypothesize that the donor artery rejected at an accelerated rate because of ischemia caused by disruption of the external vasa vasorum in conjunction with intimal hyperplasia induced by T-cell-mediated rejection that led to disruption of the Windkessel effect. Loss of this effect presented as intimal hyperplasia accelerated by ischemia causing an expedited transplant failure. Therapeutic, V.


Loss of low-level antibiotic resistance in Neisseria gonorrhoeae due to env mutations.
Mutations (env) which resulted in increased sensitivity of gonococci to diverse compounds were studied by transformation. Strains carrying an env mutation were more sensitive than wild-type strains to several antibiotics, dyes, and detergents. The env mutations resulted in complete phenotypic suppression of low-level resistance to these same drugs determined by mutation at ery. Recombination was observed in transformation crosses between various env mutants. The env locus was not linked to the cluster of antibiotic resistance genes near str and spc.


Tunable Thermal Energy Transport across Diamond Membranes and Diamond-Si Interfaces by Nanoscale Graphoepitaxy.
The development of electronic devices, especially those that involve heterogeneous integration of materials, has led to increased challenges in addressing their thermal operational temperature demands. The heat flow in these systems is significantly influenced or even dominated by thermal boundary resistance at the interface between dissimilar materials. However, controlling and tuning heat transport across an interface and in the adjacent materials has so far drawn limited attention. In this work, we grow chemical vapor-deposited diamond on silicon substrates by graphoepitaxy and experimentally demonstrate tunable thermal transport across diamond membranes and diamond-silicon interfaces. We observed the highest diamond-silicon thermal boundary conductance (TBC) measured to date and increased diamond thermal conductivity due to strong grain texturing in the diamond near the interface. Additionally, nonequilibrium molecular dynamics simulations and a Landauer approach are used to understand the diamond-silicon TBC. These findings pave the way for tuning or increasing thermal conductance in heterogeneously integrated electronics that involve polycrystalline materials and will impact applications including electronics thermal management and diamond growth.


Availability and quality of coronary heart disease family history in primary care medical records: implications for cardiovascular risk assessment.
The potential to use data on family history of premature disease to assess disease risk is increasingly recognised, particularly in scoring risk for coronary heart disease (CHD). However the quality of family health information in primary care records is unclear. To assess the availability and quality of family history of CHD documented in electronic primary care records. Cross-sectional study. 537 UK family practices contributing to The Health Improvement Network database. Data were obtained from patients aged 20 years or more, registered with their current practice between 1(st) January 1998 and 31(st) December 2008, for at least one year. The availability and quality of recorded CHD family history was assessed using multilevel logistic and ordinal logistic regression respectively. In a cross-section of 1,504,535 patients, 19% had a positive or negative family history of CHD recorded. Multilevel logistic regression showed patients aged 50-59 had higher odds of having their family history recorded compared to those aged 20-29 (OR:1.23 (1.21 to 1.25)), however most deprived patients had lower odds compared to those least deprived (OR: 0.86 (0.85 to 0.88)). Of the 140,058 patients with a positive family history recorded (9% of total cohort), age of onset was available in 45%; with data specifying both age of onset and relative affected available in only 11% of records. Multilevel ordinal logistic regression confirmed no statistical association between the quality of family history recording and age, gender, deprivation and year of registration. Family history of CHD is documented in a small proportion of primary care records; and where positive family history is documented the details are insufficient to assess familial risk or populate cardiovascular risk assessment tools. Data capture needs to be improved particularly for more disadvantaged patients who may be most likely to benefit from CHD risk assessment.


[Evaluation of the Dutch Medical Treatment Act, five years after implementation: subjective and poorly substantiated].
Five years after its implementation, the Dutch Medical Treatment Act, which regulates the doctor-patient contract, was evaluated. Two subjects were investigated: the right of the patient to be informed and to give informed consent and the way physicians deal with personal information. From a methodological point of view, this appraisal was very disappointing. At best, the evaluation report is descriptive but not evaluative: no comparative study was carried out before and after the law was implemented to ascertain effects. The Act is difficult to evaluate in practice as its goal, improving the legal position of the patient, is dogmatic. Its regulations on informed consent and agreement as well as the rules of law concerning the use of patient data for clinical research, have at times proved to be impractical even though such legal directives appear to be reasonable. The problems addressed by this law should be more widely debated and be subjected to a far more rigorous validation process.


Congenital Absence of the Pericardium: Pearls and Pitfalls.
Congenital absence of the pericardium is a very uncommon condition that may be focal, unilateral or bilateral but most frequently involves the left sided pericardium. Clinical signs and symptoms are often absent or nonspecific, overlapping with many other more common conditions. Imaging findings are distinctive if the features are sought and recognized.


Deficiency of CD11b or CD11d results in reduced staphylococcal enterotoxin-induced T cell response and T cell phenotypic changes.
The beta(2) integrin CD11a is involved in T cell-APC interactions, but the roles of CD11b, CD11c, and CD11d in such interactions have not been examined. To evaluate the roles of each CD11/CD18 integrin in T cell-APC interactions, we tested the ability of splenocytes of CD11-knockout (KO) mice to respond to staphylococcal enterotoxins (SEs), a commonly used superantigen. The defect in T cell proliferation with SEA was more severe in splenocytes from mice deficient in CD18, CD11b, or CD11d than in CD11a-deficient splenocytes, with a normal response in CD11c-deficient splenocytes. Mixing experiments showed that the defect of both CD11b-KO and CD11d-KO splenocytes was, unexpectedly, in T cells rather than in APC. Cytometric analysis failed to detect CD11b or CD11d on resting or activated T cells or on thymocytes of wild-type adult mice, nor did Abs directed to these integrins block responses in culture, suggesting that T cells educated in CD11b-KO or CD11d-KO mice were phenotypically altered. Consistent with this hypothesis, T cells from CD11b-KO and CD11d-KO splenocytes exhibited reduced intensity of CD3 and CD28 expression and decreased ratios of CD4/CD8 cells, and CD4(+) T cells were reduced among CD11b-KO and CD11d-KO thymocytes. CD11b and CD11d were coexpressed on a subset of early wild-type fetal thymocytes. We postulate that transient thymocyte expression of both CD11b and CD11d is nonredundantly required for normal thymocyte and T cell development, leading to phenotypic changes in T cells that result in the reduced response to SE stimulation.


[Synthesis and pharmacological action of TRH analog peptide (Taltirelin)].
Taltirelin hydrate[1-methyl-(S)-4,5-dihydroorotyl-L-histidyl-L-prolineamide tetrahydrate] is a new orally active thyrotropin releasing hormone (TRH) peptide analog synthetized from aspartic acid. From preclinical studies with mice and rats, Taltirelin hydrate was found to be highly stable in the blood and brain as compared with TRH. Furthermore, the CNS stimulating actions of Taltirelin hydrate such as antagonistic actions against pentobarbital-induced anesthesia and reserpine- induced hypothermia were found to be about 100 times stronger and about 8 times longer-lasting as compared with those of TRH. Meanwhile, the affinity of Taltirelin hydrate for TRH-receptors was about 10 times lower, and the endocrine action was about 5 times less potent than those of TRH. Therefore, high CNS-selectivity and long-lasting action of Taltirelin hydrate would be attributed to its high stability in the body and low affinity for TRH-receptors. Oral administrations of Taltirelin hydrate ameliorated consiousness impairment, memory impairment and motor dysfunction in several models. The clinical studies for patients with spinocerebellar degeneration are in progress.


Computational Investigation of the Effect of Lipid Membranes on Ion Permeation in Gramicidin A.
Membrane proteins are embedded in a lipid bilayer and interact with the lipid molecules in subtle ways. This can be studied experimentally by examining the effect of different lipid bilayers on the function of membrane proteins. Understanding the causes of the functional effects of lipids is difficult to dissect experimentally but more amenable to a computational approach. Here we perform molecular dynamics simulations and free energy calculations to study the effect of two lipid types (POPC and NODS) on the conductance of the gramicidin A (gA) channel. A larger energy barrier is found for the K⁺ potential of mean force in gA embedded in POPC compared to that in NODS, which is consistent with the enhanced experimental conductance of cations in gA embedded in NODS. Further analysis of the contributions to the potential energy of K⁺ reveals that gA and water molecules in gA make similar contributions in both bilayers but there are significant differences between the two bilayers when the lipid molecules and interfacial waters are considered. It is shown that the stronger dipole moments of the POPC head groups create a thicker layer of interfacial waters with better orientation, which ultimately is responsible for the larger energy barrier in the K⁺ PMF in POPC.


Grafts for hemodialysis access: results and complications.
Vascular access for hemodialysis has taxed the ingenuity of surgeons for a long time. Although the Brescia-Cimino arteriovenous fistula has become the principal access, usage of grafts become necessary when suitable artery and vein are not available for making a fistula. A total of 36 grafts for 24 patients were placed at the Riyadh Armed Forces Hospital between January 1988 and December 1989. Three of the grafts were autologous and 33 were synthetic. The forearm was the site of placement in 31 cases, four were placed in the thigh while one was placed in the arm. Twenty-eight complications were encountered during the follow-up period of which thrombosis was the commonest occurring in 14 instances (50%). A total of 23 secondary procedures were performed to prolong graft patency of which thrombectomy was the commonest (52.2%). Eight primary grafts had to be abandoned or replaced by secondary grafts. The overall patency for primary grafts was (87.5%) at six months, (79.1%) at one year and (70.8%) at two years.


Living hybrid materials capable of energy conversion and CO2 assimilation.
This paper reviews our work on the fabrication of photobiochemical hybrid materials via immobilisation of photosynthetically active entities within silica materials, summarising the viability and productivity of these active entities post encapsulation and evaluating their efficiency as the principal component of a photobioreactor. Immobilisation of thylakoids extracted from spinach leaves as well as whole cells such as A. thaliana, Synechococcus and C. caldarium was carried out in situ using sol-gel methods. In particular, a comprehensive overview is given of the efforts to find the most biocompatible inorganic precursors that can extend the lifetime of the organisms upon encapsulation. The effect of matrix-cell interactions on cell lifetime and the photosynthetic efficiency of the resultant materials are discussed. Precursors based on alkoxides, commonly used in "Chimie Douce" to form porous silica gel, release by-products which are often cytotoxic. However by controlling the formation of gels from aqueous silica precursors and silica nanoparticles acting as "cements" one can significantly enhance the life span of the entrapped organelles and cells. Adapted characteristic techniques have shown survival times of up to 5 months with the photosynthetic production of oxygen recorded as much as 17 weeks post immobilisation. These results constitute a significant advance towards the final goal, long-lasting semi-artificial photobioreactors that can advantageously exploit solar radiation to convert polluting carbon dioxide into useful biofuels, sugars or medical metabolites.


The acute effects of a rollator in individuals with COPD.
To investigate whether the acute benefits of rollator use are consistent over time in individuals with moderate to severe chronic obstructive pulmonary disease. Thirty-one stable subjects with chronic obstructive pulmonary disease (13 men, 18 women), aged 68 +/- 8 years, with a forced expiratory volume in 1 second of 0.7 +/- 0.2 L (33% +/- 12% predicted) and a baseline 6-minute walk (6MW) of 261 +/- 68 m, were recruited from a respiratory clinic after completion of a pulmonary rehabilitation program. Two 6MWs were performed at baseline, 4 weeks, and 8 weeks, one walking unaided and the other walking with the assistance of a rollator. The test order was randomly chosen at baseline, and the same test order was used at each time point. The primary outcome measures were distance walked in 6 minutes (meters), perceived dyspnea using a modified Borg scale, and number of rests taken. Subjects achieved higher 6MW distances during assisted compared with unassisted walking at baseline (292 +/- 67 vs 263 +/- 67 m), 4 weeks (296 +/- 62 vs 275 +/- 63m), and 8 weeks (283 +/- 65 vs 259 +/- 68 m) (P = .013), with no time effect (P = .5). In addition, use of a rollator resulted in a significant improvement in dyspnea (P = .004) at baseline, 4 weeks, and 8 weeks, with no time effect (P = .7). The use of a rollator also reduced the number of rests taken during the 6MW (P < .001), with no time effect (P = .9). Rollator use resulted in improvements in performance in the 6MW, which were consistent over time among individuals with moderate to severe chronic obstructive pulmonary disease who walk less than 375 m during an unaided 6MW.


The impact of laser irradiation on global stability in patients with vertebrobasilar insufficiency: a clinical report.
The purpose of our experiment was to determine whether laser stimulation can improve microcirculation in the posterior regions of the brain in patients with vertebrobasilar insufficiency (VBI). We studied 25 patients (20 female, 5 male, mean age 64) diagnosed with chronic VBI. All were evaluated using the De Klyn test, followed by qualitative assessment of stability using a Berg Balance Scale and evaluation of global stability using an electronic balance platform. A CTL-1100 low power laser was used with standard parameters. We established a protocol for laser irradiation at 5 points along the vertebral artery in the cervical region bilaterally. Irradiation was performed 10 times over two weeks. Significant improvement occurred after therapy in headache (p=0.0005), vertigo (p<0.0000), and tinnitus (p=0.0387). No significant differences were observed in nausea or nystagmus caused by head rotation. The Berg Balance Scale results showed significant differences in almost all features. There was a tendency towards improved stability in all parameters, and statistically significant differences in the total surface of support and the spread surface of support for the left foot. Laser stimulation as applied in this study can be useful in the treatment of patients with VBI. The main reason for improvement in global stability, balance, and other VBI symptoms is better blood perfusion.


Anterior visceral endoderm directs ventral morphogenesis and placement of head and heart via BMP2 expression.
In amniotes, ventral folding morphogenesis achieves gut internalization, linear heart tube formation, ventral body wall closure, and encasement of the fetus in extraembryonic membranes. Impairment of ventral morphogenesis results in human birth defects involving body wall, gut, and heart malformations and in mouse misplacement of head and heart. Absence of knowledge about genetic pathways and cell populations directing ventral folding in mammals has precluded systematic study of cellular mechanisms driving this vital morphogenetic process. We report tissue-specific mouse mutant analyses identifying the bone morphogenetic protein (BMP) pathway as a key regulator of ventral morphogenesis. BMP2 expressed in anterior visceral endoderm (AVE) signals to epiblast derivatives during gastrulation to orchestrate initial stages of ventral morphogenesis, including foregut development and positioning of head and heart. These findings identify unanticipated functions for the AVE in organizing the gastrulating embryo and indicate that visceral endoderm-expressed BMP2 coordinates morphogenetic cell behaviors in multiple epiblast lineages.


The use of time-resolved fluorescence imaging in the study of protein kinase C localisation in cells.
Two-photon-excitation fluorescence lifetime imaging (2P-FLIM) was used to investigate the association of protein kinase C alpha (PKCalpha) with caveolin in CHO cells. PKCalpha is found widely in the cytoplasm and nucleus in most cells. Upon activation, as a result of increased intracellular Ca2+ and production of DAG, through G-protein coupled-phospholipase C signalling, PKC translocates to a variety of regions in the cell where it phosphorylates and interacts with many signalling pathways. Due to its wide distribution, discerning a particular interaction from others within the cell is extremely difficult. Fluorescence energy transfer (FRET), between GFP-PKCalpha and DsRed-caveolin, was used to investigate the interaction between caveolin and PKC, an aspect of signalling that is poorly understood. Using 2P-FLIM measurements, the lifetime of GFP was found to decrease (quench) in certain regions of the cell from approximately 2.2 ns to approximately 1.5 ns when the GFP and DsRed were sufficiently close for FRET to occur. This only occurred when intracellular Ca2+ increased or in the presence of phorbol ester, and was an indication of PKC and caveolin co-localisation under these conditions. In the case of phorbol ester stimulated PKC translocation, as commonly used to model PKC activation, three PKC areas could be delineated. These included PKCalpha that was not associated with caveolin in the nucleus and cytoplasm, PKCalpha associated with caveolin in the cytoplasm/perinuclear regions and probably in endosomes, and PKC in the peripheral regions of the cell, possibly indirectly interacting with caveolin. Based on the extent of lifetime quenching observed, the results are consistent with a direct interaction between PKCalpha and caveolin in the endosomes, and possibly an indirect interaction in the peripheral regions of the cell. The results show that 2P-FLIM-FRET imaging offers an approach that can provide information not only confirming the occurrence of specific protein-protein interactions but where they occur within the cell.


Oncogenic and metastatic properties of preprotachykinin-I and neurokinin-1 genes.
Breast cancer (BC) remains the cancer with highest mortality among women in the United States. Entry of BC cells (BCCs) in bone marrow (BM) leads to poor prognosis. This review discusses studies showing interactions between BCCs and BM stroma, consequently providing BCCs with advantages of survival within BM. Myc transcription factor is investigated as a link between the transforming properties of peptides derived from the preprotachykinin-I gene (PPT-I) and Neurokinin-1 (NK1) receptor. A co-culture method previously described to model early integration of BCC in BM is used to study timeline changes of PPT-I and TGF-beta using northern analyses and a bioassay, respectively. The results show changes of both genes in BCCs and BM stroma. Relevance of these changes to homeostasis in BM is discussed. Myc has been shown to link the expressions of TGF-beta1 and PPT-I in BCCs. We now show a role for Myc in the expression of NK1. PPT-I and the chemokine SDF-1alpha induce the expression of each other through an autocrine mechanism. Since a role for Myc in SDF-1alpha-PPT-I axis has not been studied, we speculate on this finding, based on the cell-homing property of SDF-1alpha. Since Myc could be oncogenic, it might be involved in the transforming properties of PPT-I and NK1 while SDF-1alpha could be involved in cell-homing of BCCs through the regulation of PPT-I. The findings are discussed in the context of other related reports.


Tocilizumab improves oxidative stress and endothelial glycocalyx: A mechanism that may explain the effects of biological treatment on COVID-19.
We investigated the effects of tocilizumab on endothelial glycocalyx, a determinant of vascular permeability, and myocardial function in rheumatoid arthritis (RA). Eighty RA patients were randomized to tocilizumab (n = 40) or conventional synthetic disease-modifying antirheumatic drugs (csDMARDs) and glucocorticoids (GC) (n = 40) for 3 months. Forty healthy subjects with similar age and sex served as controls. We measured: (a)perfused boundary region (PBR) of the sublingual arterial microvessels (increased PBR indicates reduced glycocalyx thickness), (b)pulse wave velocity (PWV), (c)global LV longitudinal strain (GLS), (d)global work index (GWI) using speckle tracking echocardiography and e)C-reactive protein (CRP), malondialdehyde (MDA) and protein carbonyls (PCs) as oxidative stress markers at baseline and post-treatment. Compared to controls, RA patients had impaired glycocalyx and myocardial deformation markers (P < 0.05). Compared with baseline, tocilizumab reduced PBR(2.14 ± 0.2 versus 1.97 ± 0.2 μm; P < 0.05) while no significant differences were observed post-csDMARDs + GC(P > 0.05). Compared with csDMARDs + GC, tocilizumab achieved a greater increase of GLS, GWI and reduction of MDA, PCs and CRP(P < 0.05). The percent improvement of glycocalyx thickness (PBR) was associated with the percent decrease of PWV, MDA, PCs and the percent improvement of GLS and GWI(P < 0.05). Tocilizumab improves endothelial function leading to a greater increase of effective myocardial work than csDMARDs + GC through a profound reduction of inflammatory burden and oxidative stress. This mechanism may explain the effects of tocilizumab on COVID-19. CLINICAL TRIAL REGISTRATION: url: https://www.clinicaltrials.gov. Unique identifier: NCT03288584.


Robot-assisted intravertebral augmentation corrects local kyphosis more effectively than a conventional fluoroscopy-guided technique.
OBJECTIVEIntravertebral augmentation (IVA) is a reliable minimally invasive technique for treating Magerl type A vertebral body fractures. However, poor correction of kyphotic angulation, the risk of cement leakage, and significant exposure to radiation (for the surgeon, the operating room staff, and the patient) remain significant issues. The authors conducted a study to assess the value of robot-assisted IVA (RA-IVA) for thoracolumbar vertebral body fractures.METHODSThe authors performed a retrospective, single-center study of patients who had undergone RA-IVA or conventional fluoroscopy-guided IVA (F-IVA) for thoracolumbar vertebral body fractures. Installation and operating times, guidance accuracy, residual local kyphosis, degree of restoration of vertebral body height, incidence of cement leakage, rate of morbidity, length of hospital stay, and radiation-related data were recorded.RESULTSData obtained in 30 patients who underwent RA-IVA were compared with those obtained in 30 patients who underwent F-IVA during the same period (the surgical indications were identical, but the surgeons were different). The mean ± SD installation time in the RA-IVA group (24 ± 7.5 minutes) was significantly shorter (p = 0.005) than that in the F-IVA group (26 ± 8 minutes). The mean operating time for the RA-IVA group (52 ± 11 minutes) was significantly longer (p = 0.026) than that for the F-IVA group (30 ± 11 minutes). All RA-IVAs and F-IVAs were Ravi's scale grade A (no pedicle breach). The mean degree of residual local kyphosis (4.7° ± 3.15°) and the percentage of vertebral body height restoration (63.6% ± 21.4%) were significantly better after RA-IVA than after F-IVA (8.4° ± 5.4° and 30% ± 34%, respectively). The incidence of cement leakage was significantly lower in the RA-IVA group (p < 0.05). The mean length of hospital stay after surgery was 3.2 days for both groups. No surgery-related complications occurred in either group. With RA-IVA, the mean radiation exposure was 438 ± 147 mGy × cm for the patient and 30 ± 17 mGy for the surgeon.CONCLUSIONSRA-IVA provided better vertebral body fracture correction than the conventional F-IVA. However, RA-IVA requires more time than F-IVA.


The History of Stuttering by 7 Years of Age: Follow-Up of a Prospective Community Cohort.
For a community cohort of children confirmed to have stuttered by the age of 4 years, we report (a) the recovery rate from stuttering, (b) predictors of recovery, and (c) comorbidities at the age of 7 years. This study was nested in the Early Language in Victoria Study. Predictors of stuttering recovery included child, family, and environmental measures and first-degree relative history of stuttering. Comorbidities examined at 7 years included temperament, language, nonverbal cognition, and health-related quality of life. The recovery rate by the age of 7 years was 65%. Girls with stronger communication skills at the age of 2 years had higher odds of recovery (adjusted OR = 7.1, 95% CI [1.3, 37.9], p = .02), but similar effects were not evident for boys (adjusted OR = 0.5, 95% CI [0.3, 1.1], p = .10). At the age of 7 years, children who had recovered from stuttering were more likely to have stronger language skills than children whose stuttering persisted (p = .05). No evident differences were identified on other outcomes including nonverbal cognition, temperament, and parent-reported quality of life. Overall, findings suggested that there may be associations between language ability and recovery from stuttering. Subsequent research is needed to explore the directionality of this relationship.


Fold-Change-Specific Enrichment Analysis (FSEA): Quantification of Transcriptional Response Magnitude for Functional Gene Groups.
Gene expression profiling data contains more information than is routinely extracted with standard approaches. Here we present Fold-Change-Specific Enrichment Analysis (FSEA), a new method for functional annotation of differentially expressed genes from transcriptome data with respect to their fold changes. FSEA identifies Gene Ontology (GO) terms, which are shared by the group of genes with a similar magnitude of response, and assesses these changes. GO terms found by FSEA are fold-change-specifically (e.g., weakly, moderately, or strongly) affected by a stimulus under investigation. We demonstrate that many responses to abiotic factors, mutations, treatments, and diseases occur in a fold-change-specific manner. FSEA analyses suggest that there are two prevailing responses of functionally-related gene groups, either weak or strong. Notably, some of the fold-change-specific GO terms are invisible by classical algorithms for functional gene enrichment, Singular Enrichment Analysis (SEA), and Gene Set Enrichment Analysis (GSEA). These are GO terms not enriched compared to the genome background but strictly regulated by a factor within specific fold-change intervals. FSEA analysis of a cancer-related transcriptome suggested that the gene groups with a tightly coordinated response can be the valuable source to search for possible regulators, markers, and therapeutic targets in oncogenic processes. Availability and Implementation: FSEA is implemented as the FoldGO Bioconductor R package and a web-server.


No time to eat: an adaptationist account of periovulatory behavioral changes.
A comprehensive review of women's dietary behavior across the menstrual cycle suggests a drop in caloric intake around the time of ovulation; similar patterns occur in many other mammals. The periovulatory nadir is puzzling, as it is not explicable in terms of changes in the energy budget. Existing explanations in the animal literature operate wholly at the proximate level of analysis and hence do not address this puzzle. In this paper, I offer an ultimate explanation for the periovulatory feeding nadir, arguing that the decrease in the set point for satiation during the fertile period of the female cycle is an adaptation produced by natural selection in order to reduce the motivational salience of goals that compete with those directly or indirectly pertaining to mating. In support of this explanation, I adduce evidence of: a) periovulatory reductions in other ingestive behaviors, and b) periovulatory increases in motor activity and the psychological concomitants thereof.


Burrowing star-nosed moles (Condylura cristata) are not hypoxia tolerant.
Star-nosed moles (Condylura cristata) have an impressive diving performance and burrowing lifestyle, yet no ventilatory data are available for this or any other talpid mole species. We predicted that, like many other semi-aquatic and fossorial small mammals, star-nosed moles would exhibit: (i) a blunted (i.e. delayed or reduced) hypoxic ventilatory response, (ii) a reduced metabolic rate and (iii) a lowered body temperature (Tb) in hypoxia. We thus non-invasively measured these variables from wild-caught star-nosed moles exposed to normoxia (21% O2) or acute graded hypoxia (21-6% O2). Surprisingly, star-nosed moles did not exhibit a blunted HVR or decreased Tb in hypoxia, and only manifested a significant, albeit small (<8%), depression of metabolic rate at 6% O2 relative to normoxic controls. Unlike small rodents inhabiting similar niches, star-nosed moles are thus intolerant to hypoxia, which may reflect an evolutionary trade-off favouring the extreme sensory biology of this unusual insectivore.


Hong Kong Women Project a Larger Body When Speaking to Attractive Men.
In this pilot study we investigated the vocal strategies of Cantonese women when addressing an attractive vs. unattractive male. We recruited 19 young female native speakers of Hong Kong Cantonese who completed an attractiveness rating task, followed by a speech production task where they were presented a subset of the same faces. By comparing the rating results and corresponding acoustic data of the facial stimuli, we found that when young Cantonese women spoke to an attractive male, they were less breathy, lower in fundamental frequency, and with denser formants, all of which are considered to project a larger body. Participants who were more satisfied with their own height used these vocal strategies more actively. These results are discussed in terms of the body size projection principle.