Systematic review of the effects of antimicrobial cycling on bacterial resistance rates within hospital settings.
Antimicrobial resistance is an evolving phenomenon with alarming public health consequences. Antibiotic cycling is a widely known antimicrobial stewardship initiative that encompasses periodical shifts in empirical treatment protocols with the aim of limiting selective pressures on bacterial populations. We present a review of the evidence regarding the actual impact of antimicrobial cycling on bacterial resistance control within hospitals. A systematic literature review was conducted using the PubMed/MedLine, Embase, CINAHL Plus and Global Health databases. A systematic search process retrieved a sole randomised study, and so we broadened inclusion criteria to encompass quasi-experimental designs. Fifteen studies formed our dataset including seven prospective trials and eight before-and-after studies. Nine studies evaluated cycling vs. a control group and produced conflicting results whilst three studies compared cycling with antibiotic mixing, with none of the strategies appearing superior. The rest evaluated resistance dynamics of each of the on-cycle antibiotics with contradictory findings. Research protocols differed in parameters such as the cycle length, the choice of antibiotics, the opportunity to de-escalate to narrow-spectrum agents and the measurement of indicators of collateral damage. This limited our ability to evaluate the replicability of findings and the overall policy effects. Dearth of robust designs and standardised protocols limits our ability to reach safe conclusions. Nonetheless, in view of the available data we find no reason to believe that cycling should be expected to improve antibiotic resistance rates within hospitals.


Current drug withdrawal strategy in prolactinoma patients treated with cabergoline: a systematic review and meta-analysis.
Cabergoline is a recommended first-line dopamine agonist for prolactinoma treatment, which is withdrawable for some cases. However, the optimal withdrawal strategy and the accurate recurrence rate associated with cabergoline withdrawal remains uncertain. To assess the current recurrence rate of hyperprolactinemia and possible favorable factors associated with cabergoline withdrawal in prolactinoma patients. The databases of PubMed, EMBASE, and Web of Science were searched up to May 2014 to identify studies containing data of recurrent hyperprolactinemia in prolactinoma patients after cabergoline withdrawal. Meta-analysis, including sensitivity analysis, meta-regression analysis, and subgroup analysis were performed. When the patients who received cabergoline withdrawal were pooled, it was found that the hyperprolactinemia recurrence rate was 65% by a random effects meta-analysis [95% confidence interval 55-74%]. In a random effects meta-regression adjusting for optimal withdrawal strategies, CAB dose reduced to the lowest level before withdrawal was associated with treatment success (p = 0.006), whereas CAB treatment longer than 2 years showed no trend of effect (p = 0.587). Patients who received the lowest CAB dose and presented a significant reduction in tumor size before withdrawal were more likely to achieve the best success (p < 0.001). Our meta-analysis shows that hyperprolactinemia recurs after cabergoline withdrawal in a majority of patients. The probability of success favors patients who have achieved normoprolactinemia and considerable reduction in tumor size by low dose of cabergoline treatment. In addition, our study further suggests that a beneficial strategy is associated with tapering CAB dose before withdrawal but not with CAB treatment duration longer than 2 years.


Differential effects of insulin-like growth factors on scratch wound repair in respiratory epithelial cells.
Insulin-like growth factors (IGFs) I and II, being potent promoters of cellular growth and differentiation, were investigated for their effectiveness in improving the rate of scratch closure in human respiratory epithelium in vitro. Human epithelial cell lines from the nasal, bronchial, and tracheal regions were analyzed for their response to IGF-I and IGF-II, in a confluent monolayer scratch assay. IGF-binding proteins (IGFBPs) produced by certain cells are able to reduce the effectiveness of the IGFs. Consequently, the analogues LongR3 IGF-I, Des1-3 IGF-I and Arg3 IGF-I were investigated also because of their lower affinity for the IGFBPs, while still retaining unaffected affinity for the IGF-I receptor. All growth factors that were analyzed significantly improved the rate of scratch closure in bronchial and tracheal epithelial cells (p < or = 0.05). In comparison, scratch closure was markedly slower in nasal epithelial cells and IGF-I was the most effective growth factor at effecting scratch closure in these cells. The IGF-I analogues did not significantly improve scratch closure compared with IGF-I, despite the presence of IGFBP-3 in nasal, bronchial, and tracheal epithelial cells. Addition of IGF-I to wounded nasal epithelial cells increases the rate of scratch closure and therefore may have potential for improving the healing of the nasal mucosa.


DNA self-assembly nanoflower reverse P-glycoprotein mediated drug resistance in chronic myelogenous leukemia therapy.
Introduction: Chronic myelogenous leukemia (CML) is a clonal myeloproliferative disorder caused by the BCR-ABL chimeric tyrosine kinase. Vincristine (VCR) is widely used in leukemia therapy but is hindered by multidrug resistance (MDR). Methods: We prepared DNA nanoflower via self-assembly for the delivery of VCR and P-glycoprotein small interfering RNA (P-gp siRNA). Results and Discussion: The as-prepared nanoflower had a floriform shape with high loading efficiency of VCR (80%). Furthermore, the nanoflower could deliver VCR and P-gp siRNA into MDR CML cells and induce potent cytotoxicity both in vitro and in vivo, thus overcoming MDR of CML. Overall, this nanoflower is a promising tool for resistant CML therapy.


A vapor-phase deposited polymer film to improve the adhesion of electroless-deposited copper layer onto various kinds of substrates.
The adhesion of electrodeposited metal film to polymeric circuit board substrate is one of the key elements to successful miniaturization of electronic devices. However, as the size of the circuit pattern continuously decreases, a novel method is urgently required to increase the adhesion of the metal film on the substrate, especially on the smooth surface, which is critical to decrease the minimum feature size of the metal pattern. In this research, we developed an adhesion promoter layer by depositing metal chelating poly(4-vinylpyridine) (P4VP) film onto various organic and inorganic substrates via initiated chemical vapor deposition process (iCVD) to enhance the adhesion between the electroless deposited copper (Cu) layer and the substrate. The highest peel strength obtained between the electroless deposited Cu layer and P4VP coated substrate was 1.22 kgf/cm. Many advantageous characteristics of the adhesion promoter layer, including extreme thinness, the improved adhesion strength, conformal coverage, scalability of the deposition process, and short process time, will prompt the applicability of this adhesion promoter layer to industrial scale production.


Peri-operative risk factors of chronic kidney disease after liver transplantation.
Chronic kidney disease (CKD) is a frequent long-term complication after liver transplantation (LT) and is associated with poor long-term survival. The aim of our study was to identify the risk factors of developing post-transplant CKD at 1 year, during the pre-operative, peri-operative, and post-LT phases. All consecutive patients who underwent primary LT between July 2013 and February 2018 were analyzed. To assess the impact of peri- and post-operative factors on renal function at 1 year we performed a propensity score matching on gender, age of the recipient, Model for End-Stage Liver Disease (MELD) score, etiology of the hepatic disease, and estimated Glomerular Filtration Rate (eGFR) at baseline. Among the 245 patients who underwent LT, 215 had available data at one year (Y1), and 46% of them had CKD. Eighty-three patients in the CKD group and 83 in the normal renal function group were then matched. The median follow-up was 35 months (27-77). Patients with CKD at Y1 had a decreased 5-year survival compared to patients with normal renal function at one year: figures were 62% and 90%, respectively, p = 0.001. The independent predictors of CKD at Y1 were major complications (OR = 2.2, 95% CI [1.2-4.2]), p = 0.015, intensive care unit (ICU) stay > 5 days (OR = 2.2, 95% CI [1.3-5.1]), p = 0.046, ICU serum lactate level at 24 h ≥ 2.5 mmol/L (OR = 3.8 95% CI [1.1-8]), p = 0.034, need for post-LT renal replacement therapy (OR = 6.4 95% CI [1.4-25]), and MELD score ≥ 20 (OR = 2.1 95% CI [1.1-3.9]), p = 0.019. The peri-operative period has a major impact on CKD incidence. Early recognition of patients at high risk of CKD may be critical for implementation of nephroprotective measures.


The omics discovery REST interface.
The Omics Discovery Index is an open source platform that can be used to access, discover and disseminate omics datasets. OmicsDI integrates proteomics, genomics, metabolomics, models and transcriptomics datasets. Using an efficient indexing system, OmicsDI integrates different biological entities including genes, transcripts, proteins, metabolites and the corresponding publications from PubMed. In addition, it implements a group of pipelines to estimate the impact of each dataset by tracing the number of citations, reanalysis and biological entities reported by each dataset. Here, we present the OmicsDI REST interface (www.omicsdi.org/ws/) to enable programmatic access to any dataset in OmicsDI or all the datasets for a specific provider (database). Clients can perform queries on the API using different metadata information such as sample details (species, tissues, etc), instrumentation (mass spectrometer, sequencer), keywords and other provided annotations. In addition, we present two different libraries in R and Python to facilitate the development of tools that can programmatically interact with the OmicsDI REST interface.


Novel noncontact meibography with anterior segment optical coherence tomography: Hosik meibography.
To present a novel noncontact meibography system with anterior segment optical coherence tomography (OCT), which is widely used in clinics for the anterior segment (cornea, anterior chamber angle, etc.), and compare the results with preexisting infrared meibography. This research was carried out at the Seoul St Mary's Hospital with 2 volunteers. Preexisting infrared meibography was performed on the subjects, and photographs of the meibomian gland were taken again with the anterior segment OCT. With the anterior segment OCT, a tomogram of the meibomian gland could be taken and a picture of the whole meibomian gland could be taken from the infrared images for monitoring. The resolution of the preexisting infrared meibography was a pixel size of 640 × 480. In the anterior segment OCT, the meibomian glands were clearly identified just beneath the palpebral conjunctiva. There was no problem in grading the meibomian gland with the infrared images for monitoring. The resolution was 239 × 178 or 129 × 95 pixels, depending on the save option of the photograph. This novel meibography using anterior OCT yielded meibomian gland tomograms without any additional equipment, and overall infrared meibography was possible for grading. We believe this new technique will be useful in clinics for meibomian gland dysfunction and the like.


Ergonomic intervention, workplace exercises and musculoskeletal complaints: a comparative study.
Musculoskeletal disorders are among the most prevalent occupational disorders in different jobs such as office work. Some interventions such as ergonomic modifications and workplace exercises are introduced as the methods for alleviating these disorders. In this study we compared the effect of ergonomic modifications and workplace exercises on musculoskeletal pain and discomfort in a group of office workers. In an interventional study on office workers, the effect of two interventions was compared. Ergonomic modification consisted of correcting the arrangement of workstation and changing some equipment; workplace exercises included stretching exercises focusing on neck, shoulders, low back, and hand and wrist. Musculoskeletal complaints were assessed and compared before and after 1 month interventions. The frequency of musculoskeletal complaints was high before the study. Both interventions significantly reduced complaints in a similar manner except for low back pain which was reduced in exercise group more than the other group. In this study we found a beneficial short-term effect for both ergonomic modifications and stretching work-place exercises on reducing musculoskeletal pain in office workers.


[Protein content of various summer pastures].
The chemical composition of some summer pastures in Sardinia (in the surroundings of Sassari) has been examined. Very low protein content was found out (5,17 g/%). This in the grazing ruminants, particularly in the sheep, can compromise the ration's digestibility and utilization. The need to integrate the summer pasture with nitrogenous matters in emphasized.


Animal models of tuberculosis: Guinea pigs.
The progression of the disease that follows infection of guinea pigs with Mycobacterium tuberculosis displays many features of human tuberculosis (TB), and the guinea pig model of TB has been used for more than 100 years as a research tool to understand and describe disease mechanisms. Changes in the bacterial burden and pathology following infection can be readily monitored and used to evaluate the impact of TB interventions. Demonstration of the protective efficacy of vaccines in the low-dose aerosol guinea pig model is an important component of the preclinical data package for novel vaccines in development, and there is a continual need to improve the model to facilitate progression of vaccines to the clinic. Development of better tools with which to dissect the immune responses of guinea pigs is a focus of current research.


Epithelioid Cell Granulomas in Crohn's Disease Are Differentially Associated With Blood Vessels and Lymphatic Vessels: A Sequential Double Immunostaining Study.
Crohn's disease (CD) is a gastrointestinal disorder of unknown etiology. CD-specific longitudinal ulcers show an association between disease pathogenesis and vasculature dysfunction. Granulomatous lymphangitis may also contribute to CD pathogenesis; meanwhile, vasculitis is the primary CD lesion. We investigated the association between granulomas and lymphatic and blood vessels to assess the role of vasculature in CD pathogenesis. Two small and large intestine specimens were obtained from four CD patients. From each specimen, 160 sequential sections were obtained and double immunohistochemical stained to label lymphatic and blood vessels in association with granulomas. We found that 289 of 342 granulomas (85%) were associated with a lymphatic vessel and 313 of 364 granulomas (86%) were associated with a blood vessel. Although intrablood vessel granulomas were not detected, intralymphatic vessel granulomas were. In the internal region of the granuloma, we found more blood vessels than lymphatic vessels. Hence, these results cumulatively demonstrate that CD epithelioid cell granulomas are differentially associated with lymphatic and blood vessels, suggesting both as essential for the formation and maintenance of these granulomas. Moreover, both lymphatic and blood vessels may participate in granulomatous inflammation in the primary CD lesions; however, additional studies with larger numbers of participants are required to validate our findings.


Compartment Syndrome After Varicose Vein Surgery Evidenced by CT Images.
A 21-year-old man developed compartment syndrome after a varicose vein surgery. Because of a lack of appropriate diagnostic apparatus, it was not possible to measure calf pressure. The only diagnostic tool available was computed tomography (CT). With the aid of CT, faster diagnosis of the compartment syndrome was possible, leading to appropriate management. By providing unique CT images of a patient before and after having compartment syndrome and after a fasciotomy, this study could add valuable references for diagnosis of compartment syndrome using CT.


Prevalence of dermatitis in the working population, United States, 2010 National Health Interview Survey.
Prevalence patterns of dermatitis among workers offer clues about risk factors and targets for prevention, but population-based estimates of the burden of dermatitis among US workers are lacking. Data from an occupational health supplement to the 2010 National Health Interview Survey (NHIS-OHS) were used to estimate the prevalence of dermatitis overall and by demographic characteristics and industry and occupation (I&O) of current/recent employment. Data were available for 27,157 adults, including 17,524 current/recent workers. The overall prevalence rate of dermatitis among current/recent workers was 9.8% (range among I&O groups: 5.5-15.4%), representing approximately 15.2 million workers with dermatitis. The highest prevalence rates were among I&O groups related to health care. Overall, 5.6% of dermatitis cases among workers (9.2% among healthcare workers) were attributed to work by health professionals. Dermatitis affected over 15 million US workers in 2010, and its prevalence varied by demographic characteristics and industry and occupation of employment. The prevalence rate of work-related dermatitis based on the NHIS-OHS was approximately 100-fold higher than incidence rates based on the Bureau of Labor Statistics' Survey of Occupational Illness and Injury.


Adaptation to multiday ozone exposure is associated with a sustained increase of bronchoalveolar uric acid.
The phenomenon of ozone tolerance is described, but the underlying mechanisms remain unknown. We tested whether adaptation to multiday ozone exposure was related to an upregulated pulmonary antioxidant defence. Six calves were exposed to 0.75 ppm ozone, 12 h day(-1) for seven consecutive days. Pulmonary function tests and bronchoalveolar lavage (BAL) were performed before, after the first (D1), third (D3) and seventh (D7) exposure. Differential cell count, total proteins, 8-epi-PGF2alpha, glutathione and uric acid were determined in BAL. Dynamic lung compliance and arterial oxygen tension were significantly decreased and lung oedema impaired pulmonary function on D1. By repeating ozone exposures, progressive functional adaptation occurred. Ozone induced a significant increase of BAL neutrophil percentage on D1. On D3 and D7, neutrophil percentage was progressively decreased, but remained significantly elevated. BAL total proteins were significantly increased on D1 and decreased progressively until D7. 8-Epi-PGF2alpha was significantly increased on D1 and was returned to baseline on D3 and D7, whilst glutathione significantly increased on D3 and returned to baseline on D7. Uric acid was increased ten-fold on D1. On D3, uric acid was increased six-fold and was persistently elevated at D7. This study suggests that ozone adaptation of functional and inflammatory variables is accompanied with sustained BAL uric acid elevation.


Reproducible and sustained efficacy of targeted therapy with vemurafenib in patients with BRAF(V600E)-mutated Erdheim-Chester disease.
Histiocytoses are rare disorders with heterogeneous prognosis. BRAF(V600E) mutations have been observed in half of patients with Langerhans cell histiocytosis (LCH) and in 50% to 100% of patients with Erdheim-Chester disease (ECD) patients. We recently reported short-term efficacy of a BRAF inhibitor (vemurafenib) in three patients with multisystemic ECD. Vemurafenib was given to eight patients with multisystemic ECD with CNS and/or cardiac involvement. All patients were refractory to first-line treatment and harbored a BRAF(V600E) mutation. Four patients also had LCH lesions. Positron emission tomography (PET) scan response at month 6 was used as the main evaluation criterion. Secondary evaluation criteria were comparison at baseline and at last visit of PET and of cardiovascular and cerebral infiltrations (computed tomography scan and magnetic resonance imaging [MRI]). All patients were partial metabolic responders at 6 months of vemurafenib, and the median reduction in maximum standardized uptake value was 63.5% (range, 41.3% to 86.9%). Evaluation of cardiac and aortic infiltrations showed that seven patients had a partial response and one patient had stable disease according to surface measurements derived from RECIST criteria. The four patients with infratentorial CNS infiltration had an objective decrease of the lesions on MRI. All patients had an improvement of general symptoms and a persistent response to vemurafenib, with a median follow-up time of 10.5 months (range, 6 to 16 months). Skin adverse effects were frequent and severe. Vemurafenib has an objective and sustained efficacy in BRAF(V600E)-mutated ECD as second-line therapy. In contrast to melanoma, no resistance has emerged to date after 6 to 16 months.


Short pulse close to round-trip time generated by cavity-less high-gain Nd:GdVO4 bounce geometry.
In this paper, pulsed output with pulse-widths approaching the round-trip time were generated by utilizing a cavity-less high-gain Nd:GdVO4 bounce geometry. By adopting an EOQ (electro-optics Q-switch) device, pulse-widths of 1.36 ns, 1.82 ns, and 2.39 ns were achieved at three effective cavity lengths, respectively. All these pulse-widths were close to the round-trip time of corresponding effective cavity lengths. Moreover, watt-level output power at kHz-level repetition rate was achieved, as well as the good beam quality with M2 factor less than 1.3. The output had a time-averaged continuous spectrum with 10 dB linewidth of 0.2 nm.


Efficacy and safety of fetal posterior cerebral artery stented coil embolization for fetal posterior cerebral aneurysms.
Aneurysms at the origin of the fetal posterior cerebral artery (fPCA) often show fPCA bifurcation from the aneurysm dome, impeding complete embolization and dense coil packing. The recanalization rate for fPCA aneurysms is therefore high. This study aimed to evaluate the efficacy and safety of stenting into fPCA for aneurysms with fPCA incorporated into the aneurysm to determine whether stenting can provide effective embolization results and prevent recanalization. A total of 19 consecutive coil embolization procedures between February 2012 and June 2022 for unruptured fPCA aneurysms with fPCA branching from the dome of the aneurysm were divided into two groups: non-stenting (NS) group (n = 11) and stenting into fPCA (PS) group (n = 8). Data were obtained retrospectively and compared regarding embolization results, complications, and recanalization. Compared with the NS group, the PS group achieved significantly higher complete occlusion rate and packing density (p < 0.001, p = 0.01, respectively). No symptomatic complications were observed in the PS group. Both immediately after stenting and at the 1-year follow-up, no stent kinking, stenosis, occlusion, or malposition were observed in any patients in the PS group. During 1-year follow-up, the cumulative minor and major recanalization-free rate after coil embolization for fPCA aneurysms were significantly higher in the PS group compared with the NS group (p = 0.022, 0.0024, respectively). Stenting into fPCA for aneurysms with fPCA incorporated into the aneurysm achieved high-density complete embolization without increasing complications, and prevented recanalization. The fPCA stent-assisted coil embolization can offer an alternative treatment for fPCA aneurysms.


A holocene perspective on algal mercury scavenging to sediments of an Arctic lake.
Anthropogenic activities have increased the amount of mercury (Hg) transported atmospherically to the Arctic. At the same time, recent climate warming is altering the limnology of arctic lakes and ponds, including increases in aquatic primary production. It has been hypothesized that climate-driven increases in aquatic production have enhanced Hg scavenging from the water column, and that this mechanism may account for much of the recent rise in lake sediment Hg. Here, we test the relationship between climate, algal production, and sediment Hg using a well-dated and multiproxy lake sediment record spanning the Holocene from Lake CF3 (Baffin Island, Nunavut, Canada). During the early Holocene, peak (summer) insolation drove July air temperatures higher than present, and resulted in increased autochthonous primary production as recorded by total organic matter, spectrally inferred Chl-a, diatom abundance, and carbon stable isotopic signatures. However, there are no relationships between any of these proxies and sediment Hg concentrations during this interval. Given that the behavior of preindustrial Hg was relatively stable during past intervals of naturally mediated high production, we surmise that postindustrial increases in Hg accumulation within CF3 reflect a multiplicative effect of atmospheric deposition of anthropogenic Hg and increased sedimentation rates.


Imipramine enhancement of pentobarbital toxicity in rats.
The toxicity of pentobarbital was examined in male Wistar rats pretreated with a non-toxic dose of imipramine (10 mg/kg, po). Pentobarbital (70 mg/kg, ip) lethality was enhanced up to 6 hr after imipramine administration, and pentobarbital (45 mg/kg, ip) sleeping time was prolonged up to 12 hr after imipramine. Physiological measurements showed that imipramine pretreatment 2 hr prior to pentobarbital (70 mg/kg, ip) enhanced barbiturate depression in mean blood pressure, oxygen consumption and respiration rate, but not in heart rate or back skin temperature. Analysis of brain radioactivity after [14C] pentobarbital indicated that these effects of imipramine were not solely the result of inhibition of liver metabolism.


Design of DNA-conjugated polypeptide-based capture probes for the anchoring of proteins to DNA matrices.
A new method for protein surface functionalization was developed that utilizes DNA-conjugated artificial polypeptides to capture recombinant target proteins from the solution phase and direct their deposition onto DNA-functionalized matrices. Protein capture is accomplished through the coiled-coil association of an engineered pair of heterodimeric leucine zippers. Incorporating half of the zipper complex directly into the polypeptides and labeling these polymers with ssDNA enables the polypeptide conjugates to form intermediate linkages that connect the target proteins securely to DNA-functionalized supports. This synthetic route provides an important alternative to conventional DNA-conjugation techniques by allowing proteins to be outfitted site-specifically with ssDNA while minimizing the need for postexpression processing. We demonstrate these attributes by (i) using the capture probes to prepare protein microarrays, (ii) demonstrating control over enzyme activity via deposition of DNA, and, (iii) synthesizing finite-sized, multiprotein complexes that are templated on designed DNA scaffolds in near quantitative yield.


[Ankylosing spondylitis with mononeuritis and possible multiple sclerosis (author's transl)].
A patient with ankylosing spondylitis developed a neurological disorder suggesting multiple sclerosis. An increased level of gammaglobulin was detected in the analysis of the cerebro spinal fluid. The response to steroid therapy, however, was unusual to that of multiple sclerosis since clinical manifestations disappeared shortly after, recurred some months later after discontinuance of the treatment, and subside again when the administration of corticosteroids was repeated. On the other hand, the patient developed an acute right peroneal neuritis with slowness of the conduction velocity. Although the association of a clinical picture resembling multiple sclerosis with ankylosing spondylitis has been reported, there are a few, and sometimes poorly documented, published cases. The literature is reviewed and the possibility of a relationship between the isolated peripheral neuritis and the underlying disease is suggested.


On the Tethyida (Porifera, Demospongiae) from Bahia State, northeast Brazil, with descriptions of two new species, taxonomic appointments and new records.
The recently proposed order Tethyida is characterized by the presence of megasclere styles, tylostyles or oxeas arranged in tracts ending as bouquets at or near the surface, and microsclere euasters. Two new species are described from the shallow coastal reefs (0-10 m) of Bahia, Brazil. Timea kamasary sp. nov. is represented by thin sciaphylous specimens with three categories of spicules: tylostyles, spined spheroxyasters and spined/smooth oxyasters in varied sizes. This species differs from Timea unistellata (Topsent, 1892) by having a different category of oxyasters. Tethya bitylastra sp. nov. is characterized by having strongyloxeas I and II, spherasters, oxyasters I and II, strongylasters and two categories of tylasters. This new species differs from Tethya maza Selenka, 1879 by having a second category of tylaster. Furthermore, we present taxonomic appointment for Timea berlincki (Leite, Fonseca, Leal Hajdu, 2015) and Tethya maza and the first record of Timea stenosclera (Hechtel, 1969) for the Southwest Atlantic.


Optimal learning rules for discrete synapses.
There is evidence that biological synapses have a limited number of discrete weight states. Memory storage with such synapses behaves quite differently from synapses with unbounded, continuous weights, as old memories are automatically overwritten by new memories. Consequently, there has been substantial discussion about how this affects learning and storage capacity. In this paper, we calculate the storage capacity of discrete, bounded synapses in terms of Shannon information. We use this to optimize the learning rules and investigate how the maximum information capacity depends on the number of synapses, the number of synaptic states, and the coding sparseness. Below a certain critical number of synapses per neuron (comparable to numbers found in biology), we find that storage is similar to unbounded, continuous synapses. Hence, discrete synapses do not necessarily have lower storage capacity.


Incidence of exertional rhabdomyolysis in polo horses in the USA and the United Kingdom in the 1999/2000 season.
A questionnaire was used to determine the incidence of exertional rhabdomyolysis and the factors that might have contributed to its occurrence among 423 polo horses in 11 yards. The yards were selected at random, six of them with 111 horses, in north-eastern USA, and five with 312 horses in south-east England. During the 1999/2000 season the incidence of the condition was 7.3 per cent (9 per cent in the USA and 6.7 per cent in England). The incidence in mares was similar in the two countries, 8.4 per cent in the USA and 8.0 per cent in England, but the incidence in geldings in the USA (10 per cent) was much higher than in England (1.5 per cent). A more excitable than average temperament was reported in 71 per cent of the horses with the condition, and most cases occurred after a game (chukka) in which the horse was perceived to be not fit enough for the level of play demanded. Sixty-four per cent of the cases occurred early in the season and on average each episode resulted in the loss of 7.6 training days.


Physiological interaction between alpha-adducin and WNK1-NEDD4L pathways on sodium-related blood pressure regulation.
The kidney plays an important role in salt and blood pressure (BP) homeostasis. In previous studies, variants in the genes for alpha-adducin (ADD1), WNK1, and NEDD4L, which all regulate renal sodium absorption, have been associated with increased BP. However, findings have been inconsistent. We tested whether this is because of physiological interactions between the effects of variants in these genes. We assessed the single and combined effects of the ADD1 (Gly460Trp), WNK1 (rs880054 A/G), and NEDD4L (rs4149601 G/A) polymorphisms on renal and BP response to an acute Na load (n=344 subjects), BP decrease after 1 month of treatment with 12.5 mg of hydrochlorothiazide (n=193), and ambulatory 24-hour BP (n=690). Individually, the variants showed modest effects on some of the studied phenotypes. We found the ADD1 Trp allele to be permissive for the effects of variants of the other genes. In combination, the same variants (ADD1 Trp/WNK1 GG/Nedd4L GA+AA) showed a consistent effect on renal Na handling (P=0.009) and acute BP response to a saline infusion (P=0.021), BP lowering after thiazide treatment (P=0.008), and nocturnal systolic BP (P=0.044). Physiological interaction between the ADD1 and WNK1-NEDD4L pathways influences the effects of variants in these genes on sodium-related BP regulation. Relatively common alleles in the ADD1, WNK1, and NEDD4L genes when present in combination may have significant effects on renal sodium handling, BP, and antihypertensive response to thiazides.


Sleep Rate Mode of Pacemaker-Dependent Patients with Sick Sinus Syndrome Increases Dipper Blood Pressure and Dipper Heart Rate Patterns.
Cardiovascular event rates of patients with a dipper blood pressure (BP) and dipper heart rate (HR) pattern are lower than those of patients with nondipper BP and HR patterns. However, how the pacemaker mode affects the diurnal BP and HR patterns remains unclear.We enrolled nine patients (average age 74.4 ± 6.6 years, 4 males and 5 females) with sick sinus syndrome who required atrial pacing. We investigated sequential 6-month pacing regimens (DDD mode at 60 bpm and sleep rate mode). We set the lower rate of sleep rate mode as follows: 60 bpm during the daytime and 50 bpm during the nighttime. The order of pacing mode was randomized, with crossover design. Ambulatory BP monitoring was performed at baseline, 6 months, and 12 months, BP category was classified into four groups (extreme dipper, dipper, nondipper, and riser pattern), and HR was classified into dipper and nondipper patterns.Nighttime HR during the sleep rate mode was significantly lower than that at DDD (57.1 ± 6.2 versus 63.5 ± 3.8 bpm, P = 0.001). The dipper HR pattern was increased in the sleep rate mode compared with those at baseline or DDD mode (versus baseline: 89% versus 44%, P = 0.035; versus DDD: 89% versus 22%, P = 0.004). The dipper BP pattern significantly increased in the sleep rate mode compared with the baseline (56% versus 11%, P = 0.035), but the difference between the sleep rate mode and DDD mode was statistically marginal (56% versus 22%, P = 0.081).The pacemaker settings in the sleep rate mode increased the dipper HR and BP patterns in pacemaker-dependent patients with sick sinus syndrome.


In vivo release of cyanide from sodium nitroprusside.
Brain cytochrome oxidase activity was measured after the in vitro addition of potassium cyanide (KCN) or sodium nitroprusside (SNP). Activity of cytochrome oxidase was sensitive to KCN; however, this activity was unaffected by SNP. In SNP- and KCN-treated animals brain cytochrome oxidase activities were measured. At 3 min after SNP injection, inhibition of the enzymatic activity was the same as 1 min after KCN injection. Time to death for SNP-treated animals was longer than for KCN-treated animals. These data suggest that cyanide was released in vivo from SNP and that time was necessary for this release to occur.


Netnography: A novel methodology for nursing research.
The aim of this paper is to critically reflect on our team's experience of using netnography to explore vaccine-hesitant parents and pregnant women, a group who have traditionally been difficult to recruit to research studies and a methodology that is underutilized in nursing research. This paper takes the form of a discussion paper that will utilize data obtained from a qualitative netnographic study. Relevant literature was searched including 2015-2023. This paper utilized data obtained from a qualitative study that used netnography as methodology and an online minable data source. Netnography is a relatively new methodology that uses the online environment to explore digital cultures and study networked society. It pays particular attention to cultural insights and conditions that impact the human experience. This methodology is particularly relevant to nursing research which is often humanistic and always conducted to ensure optimal patient outcomes. Using netnography for the first time has resulted in four main insights. These include the adaptability of the process; the creativity involved in designing the site; the ready acceptance of the site by participants and the co-creation knowledge that resulted. Netnography is a creative methodology that was successful in accessing and engaging the vaccine-hesitant community, a group who are often marginalized. Netnography has the advantage of using a platform that is familiar and safe for many people and provides access to an extensive minable data source.


Decrement Evoked Potential Mapping: Basis of a Mechanistic Strategy for Ventricular Tachycardia Ablation.
Substrate-based mapping for ventricular tachycardia (VT) ablation is hampered by its inability to determine critical sites of the VT circuit. We hypothesized that those potentials, which delay with a decremental extrastimulus (decrement evoked potentials or DEEPs), are more likely to colocalize with the diastolic pathways of VT circuits. DEEPs were identified in intraoperative left ventricular maps from 6 patients with ischemic cardiomyopathy (total 9 VTs) and were compared with late potential (LP) and activation maps of the diastolic pathway for each VT. Mathematical modeling was also used to further validate and elucidate the mechanisms of DEEP mapping. All patients demonstrated regions of DEEPs and LPs. The mean endocardial surface area of these potentials was 18±4% and 21±6%, respectively (P=0.13). The mean sensitivity for identifying the diastolic pathway in VT was 50±23% for DEEPs and 36±32% for LPs (P=0.31). The mean specificity was 43±23% versus 20±8% for DEEP and LP mapping, respectively (P=0.031). The electrograms that displayed the greatest decrement in each case had a sensitivity and specificity for the VT isthmus of 29±10% and 95±1%, respectively. Mathematical modeling studies recapitulated DEEPs at the VT isthmus and demonstrated their role in VT initiation with a critical degree of decrement. In this preliminary study, DEEP mapping was more specific than LP mapping for identifying the critical targets of VT ablation. The mechanism of DEEPs relates to conduction velocity restitution magnified by zigzag conduction within scar channels.


Prerequisite competencies for third-year clerkships: an interdisciplinary approach.
The Collaborative Curriculum Project (CCP) is one of three components of the Family Medicine Curriculum Resource Project (FMCRP), a federally funded effort to provide resources for medical education curricula at the beginning of the 21st century. Medical educators and staff from public and private geographically distributed medical schools and national specialty organizations in family medicine, internal medicine, and pediatrics developed by consensus essential clinical competencies that all students should have by the beginning of the traditional clerkship year. These competencies are behaviorally measurable and organized into the domains used for the Accreditation Council for Graduate Medical Education (ACGME) core competencies. Exemplary teaching, assessment, and faculty development resources are cited, and attention is given to budgetary considerations, application to diverse populations and settings, and opportunities for integration within existing courses. The CCP also developed a subset of competencies meriting higher priority than currently provided in the pre-clerkship years. These priority areas were empirically validated through a national survey of clerkship directors in six disciplines. The project's documents are not intended to prescribe curricula for any school but rather to provide curricular decision makers with suggestions regarding priorities for allocation of time and resources and detailed clinical competency statements and other resources useful for faculty developing clinical courses in the first 2 years of medical school.


An examination of the roles played by early adolescent children in interactions with their local food environment.
The purpose of this study was to examine how pre- and early adolescent (10-14 years old) children from a wide range of neighbourhoods interact with their local food environment (FE), with a focus on the foods and food sources they access and their locations. Children in this age group are developing independence and mobility within (and beyond) their home neighbourhoods but are somewhat geographically bound as they cannot yet drive. This research consists of qualitative interviews with 31 children (15 males, 16 females) aged 10-14 years living in socio-economically diverse neighbourhoods across Saskatoon, SK. A thematic analysis was conducted. Children's descriptions of what constitutes their neighbourhood FE were varied, ranging from a couple of city blocks to several kilometres from home. Children were familiar with the types of establishment that sell food within their perceived neighbourhood. When children purchased their own food they most frequently cited buying snacks such as ice cream, candy and slushes, and the majority of these purchases were made in convenience stores, gas stations and grocery stores. Few children reported frequenting fast-food or other restaurants without adults, and when they did it was usually to buy snacks such as French fries and ice cream rather than meals. Our results highlight the importance of interventions targeted to this age group, in which personal food choices were reported almost exclusively as being energy- but not nutrient-dense snack foods.


Comparison of chest computed tomography features between pulmonary tuberculosis patients with culture-positive and culture-negative sputum for non-mycobacteria: A retrospective observational study.
Although complication with non-mycobacterial pneumonia among patients with pulmonary tuberculosis (TB) may lead to poor prognosis, discrimination between TB complicated with and without non-mycobacterial pneumonia using radiological imaging has not been fully elucidated. We aimed to clarify the differences in chest computed tomography (CT) features between pulmonary TB patients with culture-positive and culture-negative sputum for non-mycobacteria.We retrospectively included consecutive patients admitted to our hospital from January 2013 to December 2015 for bacteriologically-confirmed pulmonary TB, who were tested by sputum culture for non-mycobacteria, and who underwent chest CT within 2 weeks before or after admission. Chest CT features were compared between pulmonary TB patients who had positive non-mycobacterial cultures and in those who had not.Of 202 patients with pulmonary TB, 186 (92%) were tested by sputum culture for non-mycobacteria and underwent chest CT. Among these, non-mycobacteria were isolated in 118 patients (63%), while 68 patients (37%) had negative cultures. Patients with a positive culture for non-mycobacteria were significantly older and had lower levels of physical activity and albumin, higher levels of C-reactive protein, and a greater number of respiratory failures. By CT, emphysematous lesions, ground-glass opacities, airspace consolidation, air-bronchogram, interlobular septal thickening, bronchiectasis, pleural effusion, pleural thickening, and lymph node enlargement were more frequently in patients with a positive culture for non-mycobacteria. These chest CT features could be helpful for detecting complication with non-mycobacterial pneumonia in patients with pulmonary TB.


A short, novel, and cheaper procedure for oligonucleotide synthesis using automated solid phase synthesizer.
Dimethylthiuram disulfide (DTD) has been developed as an efficient thiolation reagent during automated synthesis of oligonucleotides using phosphoramidite chemistry. Simultaneous thiolation and capping was accomplished by mixing DTD with capping solution B, which saved 20% of solvent consumption and compressed the four-step synthesis cycle to three. Large-scale (1 mmol) synthesis of phosphorothioate oligonucleotides has been demonstrated with excellent yield and purity.


Decay kinetic properties of atoms in photonic crystals with absolute gaps.
Decay kinetic properties of a two-level atom near the band edges of photonic crystals (PCs) with absolute gaps are studied based on the Green's function expression for the evolution operator. The local coupling strength between the photons and an atom is evaluated by an exact numerical method. It is found that the decay behavior of an excited atom can be fundamentally changed by the variation of the atomic position: Weisskopf-Wigner and non-Weisskopf-Wigner decay phenomena occur at different atomic positions in the PCs as a result of a significant difference in the local coupling strength. Our finding implies that it is possible to engineer the luminescence spectrum by controlling the atomic position.


Successful Use of EPOCH-R in 2 Young Adult Patients With Burkitt Lymphoma and Acute Kidney Injury: A Case Report.
Pediatric Burkitt lymphoma has historically been treated with intensive methotrexate-based chemotherapy, which improves patient survival while causing severe toxicities. Young patients typically have better outcomes with intensive therapies, while adults and immunocompromised patients have higher toxicities and worse outcomes. Newer treatment regimens, including etoposide, prednisone, vincristine, cyclophosphamide, doxorubicin, rituximab (EPOCH-R), show promise for these patients. However, few studies exist to demonstrate efficacy and improved toxicity profile with EPOCH-R. We present 2 cases: a 25-year-old male with Down syndrome and an 18-year-old male with Burkitt lymphoma and significant renal injury who were successfully treated with EPOCH-R with minimal toxicities.


[Methodologic and strategic considerations in schizophrenia research].
So far, schizophrenia can only be regarded as a heterogeneous syndrome in view of the fact that both concept and phenomenology themselves are heterogeneous and also that aetiology and pathogenesis are likewise largely unknown. Furthermore, the diagnosis "schizophrenia" is merely a convention and nothing more, which, in turn, considerably hampers aetiopathogenetic research. Hence, we cannot expect highly valid results if we examine the nosological specificity of certain variables by means of internosological comparisons. However, a clinically more relevant approach could be the examination of the clinical validity especially the prognostic and predictive validity of variables, even though such examination has so far not led to convincing results in individual cases. A more striking relevance for aetiopathogenetic groupings could be obtained, above all, by a "reversal of the dependence of variables". This reversal should concern variables that are as homogeneous and clearly defined as possible and are reliably measurable. This applies mainly if by "horizontal" characterisation a) they have proved to be time-stable trait markers on the grounds of prospective intraindividual comparisons; b) furthermore, if by being present before the diseased state is manifest they have proved to be vulnerability markers either retrospectively by anamnesis of relevant signs and symptoms or prospectively in still (?) healthy subjects by means of high-risk studies; c) and, finally, if they are found to be markers in the true sense of the word on the grounds of their mass occurrence in healthy blood relatives, i.e. as variables under genetic control. We think that mainly such variables appear to be promising for an aetiopathogenetically oriented "vertical" strategy. This strategy aims via multidisciplinary multilevel analyses, utilising strategies, techniques and results of the rapidly developing neurosciences, at establishing connections of variables between various levels, as the "uppermost" of which we can consider to be the clinico-psychopathological level and as "lowermost" the molecular-biological level. This is discussed on the basis of examples.


Malignant soft tissue sarcoma of the shoulder treated by surface mould brachytherapy boost in an adjuvant setting.
Soft tissue sarcomas of the extremities account for half of all soft tissue sarcomas. Radiotherapy and surgery have been the standard modalities in the treatment of this type of cancer. Brachytherapy can be used as the sole therapy, if the target volume is localized and easily accessible. This work reports three cases of shoulder soft tissue sarcomas with positive deep resected margins, treated with a combination of external beam radiotherapy and surface mould brachytherapy boost technique. Between January and June 2014, three patients received brachytherapy with sites close to the shoulder, and post-surgery involved deep resected margins. Each mould was made on a base of thermoplastic, over which dental wax was coated and catheters implanted. The target volume was defined as the tissue covering the tumor bed with lateral margins of 2-2.5 cm and depth of 1-1.5 cm. Treatment planning was computed tomography-based and dose prescribed was 85-100% isodose. Treatments has been delivered twice daily, six hours interval, and a review of reactions evaluated. Volume receiving more than 150% of the prescribed dose has been limited to less than 2%, and that above 200% to be inside the mould. Brachytherapy equivalent dose at 2 Gy per fraction (EQD2) of these patients was 24 and 28.6 Gy. Maximum dose to organ at risk (OAR) (2 cc of OAR) ranged between 55-87% of prescribed dose, with a median dose being 80%. All cases had only grade 1 post-radiotherapy skin immediate reactions, which resolved within four weeks. In all patients, no treatment failures were noted at nearly 2-years post-irradiation. Surface mould brachytherapy in soft tissue sarcomas could be a useful alternative to interstitial brachytherapy, especially where the target volume is superficially extensive with underlying critical structures, and where catheter placement may be difficult, such as the shoulder.


Structure and physiology of calpain, an enigmatic protease.
Calpain is one of the most extensively studied proteinases (1). Although its enzymatic and structural properties have been well characterized, neither the structure-function relationship nor physiological functions are completely understood. In recent years, increasing numbers of molecules showing sequence similarity to calpain have been identified and the concept of a "calpain super family" has become general (2, 3). The term "calpain" originally meant a Ca(2+)-activated, neutral, and intracellular cysteine proteinase, although a proteinase domain similar to that of calpain is a prerequisite for a member of the "calpain super family" (4, 5). The molecular diversity of calpain has attracted interest to its structural and functional transition during evolution. Here we describe the state of current knowledge, progress, and clues to the next phase of calpain research.


Physiological Aging Influence on Brain Hemodynamic Activity during Task-Switching: A fNIRS Study.
Task-switching (TS) paradigm is a well-known validated tool useful for exploring the neural substrates of cognitive control, in particular the activity of the lateral and medial prefrontal cortex. This work is aimed at investigating how physiological aging influences hemodynamic response during the execution of a color-shape TS paradigm. A multi-channel near infrared spectroscopy (fNIRS) was used to measure hemodynamic activity in 27 young (30.00 ± 7.90 years) and 11 elderly participants (57.18 ± 9.29 years) healthy volunteers (55% male, age range: (19-69) years) during the execution of a TS paradigm. Two holders were placed symmetrically over the left/right hemispheres to record cortical activity [oxy-(HbO) and deoxy-hemoglobin (HbR) concentration] of the dorso-lateral prefrontal cortex (DLPFC), the dorsal premotor cortex (PMC), and the dorso-medial part of the superior frontal gyrus (sFG). TS paradigm requires participants to repeat the same task over a variable number of trials, and then to switch to a different task during the trial sequence. A two-sample t-test was carried out to detect differences in cortical responses between groups. Multiple linear regression analysis was used to evaluate the impact of age on the prefrontal neural activity. Elderly participants were significantly slower than young participants in both color- (p < 0.01, t = -3.67) and shape-single tasks (p = 0.026, t = -2.54) as well as switching (p = 0.026, t = -2.41) and repetition trials (p = 0.012, t = -2.80). Differences in cortical activation between groups were revealed for HbO mean concentration of switching task in the PMC (p = 0.048, t = 2.94). In the whole group, significant increases of behavioral performance were detected in switching trials, which positively correlated with aging. Multivariate regression analysis revealed that the HbO mean concentration of switching task in the PMC (p = 0.01, β = -0.321) and of shape single-task in the sFG (p = 0.003, β = 0.342) were the best predictors of age effects. Our findings demonstrated that TS might be a reliable instrument to gather a measure of cognitive resources in older people. Moreover, the fNIRS-related brain activity extracted from frontoparietal cortex might become a useful indicator of aging effects.


EU marker polycyclic aromatic hydrocarbons in food supplements: analytical approach and occurrence.
Several food supplements comprising botanical, oil and bee products collected from retail markets in different countries were tested for the occurrence of 4 EU marker Polycyclic aromatic hydrocarbons (PAHs; benz[a]anthracene, chrysene, benzo[b]fluoranthene and benzo[a]pyrene). A robust GC/MS-based stable-isotope dilution method was used taking into account the differences in the type of matrices. The accuracy of the results was assessed by implementing several quality control tools. Sixty-eight samples of 94 analysed products exceeded the level of 0.5 μg/kg for the sum of the four EU marker PAHs (ΣPAH4). Benzo[a]pyrene exceeded the limit of quantification in 49 samples. The PAH with the highest abundance in all products was chrysene. On average, propolis extracts and other bee products showed relatively high levels of ΣPAH4 (mean 188.2 μg/kg), whereas the contamination levels of fish oil supplements were very low or mostly undetectable. Considerably high ΣPAH4 amounts found in some samples could remarkably increase the daily exposure of consumers to PAHs, demonstrating the need for continuous monitoring of ΣPAH4 in food supplements.


Trait anxiety modulates fronto-limbic processing of emotional interference in borderline personality disorder.
Previous studies of cognitive alterations in borderline personality disorder (BPD) have yielded conflicting results. Given that a core feature of BPD is affective instability, which is characterized by emotional hyperreactivity and deficits in emotion regulation, it seems conceivable that short-lasting emotional distress might exert temporary detrimental effects on cognitive performance. Here we used functional magnetic resonance imaging (fMRI) to investigate how task-irrelevant emotional stimuli (fearful faces) affect performance and fronto-limbic neural activity patterns during attention-demanding cognitive processing in 16 female, unmedicated BPD patients relative to 24 age-matched healthy controls. In a modified flanker task, emotionally negative, socially salient pictures (fearful vs. neutral faces) were presented as distracters in the background. Patients, but not controls, showed an atypical response pattern of the right amygdala with increased activation during emotional interference in the (difficult) incongruent flanker condition, but emotion-related amygdala deactivation in the congruent condition. A direct comparison of the emotional conditions between the two groups revealed that the strongest diagnosis-related differences could be observed in the dorsal and, to a lesser extent, also in the rostral anterior cingulate cortex (dACC, rACC) where patients exhibited an increased neural response to emotional relative to neutral distracters. Moreover, in the incongruent condition, both the dACC and rACC fMRI responses during emotional interference were negatively correlated with trait anxiety in the patients, but not in the healthy controls. As higher trait anxiety was also associated with longer reaction times (RTs) in the BPD patients, we suggest that in BPD patients the ACC might mediate compensatory cognitive processes during emotional interference and that such neurocognitive compensation that can be adversely affected by high levels of anxiety.


Optimal trajectory for the atlantooccipital transarticular screw.
Radiologic evaluation of computed tomography (CT) scans using screw insertion simulation software. To investigate the optimal entry point and trajectory of atlantooccipital transarticular screws. To our knowledge, no large series focusing on the placement of atlantooccipital transarticular screws have been published. We used 1.0-mm sliced CT scans and 3-dimensional screw trajectory software to simulate 4.0-mm screw placement. Four entry points were evaluated. Screw placement success rate, safe range of medial angulation, and screw length using each entry point were determined. CT scans of 126 patients were evaluated, for a total of 252 screws for each entry point. On simulation, the 2 lateral entry points showed significantly higher success rates and safe range of medial angulation than the 2 middle points. The 2 lateral entry points had similar success rates (98.0% for anteriolateral (AL) point and 97.6% for posteriolateral (PL) point). Although the safe range of medial angulation was significantly wider for the AL point (26.1 degrees) than for the PL point (23.7 degrees), the screw lengths were significantly longer for the PL point (32.6 mm) than for the AL point (29.4 mm). For both points, 30 degrees of medial angulation led to highest rate of successful screw placement, but the rate was only 79.4% and 80.2%, respectively. Although there was no significant difference in success rates between AL and PL points, PL is likely the best entry point. Although 30 degrees medial and approximately 5 degrees upward angulation led to the highest rate of successful screw placement, the rate was only around 80%. Given the wide individual variation, we recommend that a preoperative 3-dimensional CT scan be obtained when attempting atlantooccipital transarticular screw fixation.


Suppression of the Sendai virus M protein through a novel short interfering RNA approach inhibits viral particle production but does not affect viral RNA synthesis.
Short RNA interference is more and more widely recognized as an effective method to specifically suppress viral functions in eukaryotic cells. Here, we used an experimental system that allows suppression of the Sendai virus (SeV) M protein by using a target sequence, derived from the green fluorescent protein gene, that was introduced in the 3' untranslated region of the M protein mRNA. Silencing of the M protein gene was eventually achieved by a small interfering RNA (siRNA) directed against this target sequence. This siRNA was constitutively expressed in a cell line constructed by transduction with an appropriate lentivirus vector. Suppression of the M protein was sufficient to diminish virus production by 50- to 100-fold. This level of suppression had no apparent effect on viral replication and transcription, supporting the lack of M involvement in SeV transcription or replication control.


An Examination of New Paradigms for Spline Approximations.
Lavery splines are examined in the univariate and bivariate cases. In both instances relaxation based algorithms for approximate calculation of Lavery splines are proposed. Following previous work Gilsinn, et al. [7] addressing the bivariate case, a rotationally invariant functional is assumed. The version of bivariate splines proposed in this paper also aims at irregularly spaced data and uses Hseih-Clough-Tocher elements based on the triangulated irregular network (TIN) concept. In this paper, the univariate case, however, is investigated in greater detail so as to further the understanding of the bivariate case.


[Autopsy practised in modern China].
It's very difficult for autopsy to develop in modern China. Two autopsy rules issued by Ministry of Internal Affairs were of epochal significance. Although Society on Anatomy had been set up by western medical workers, and there were four people willing to offer their own remains after death for autopsy, it was still very difficult to obtain a cadaver for autopsy actually. The main barrier still lay in the feudal morality. Moreover, incomplete law also contributed a factor.


Characterisation of Co@Fe3O4 core@shell nanoparticles using advanced electron microscopy.
Cobalt nanoparticles were synthesised via the thermal decomposition of Co2(CO)8 and were coated in iron oxide using Fe(CO)5. While previous work focused on the subsequent thermal alloying of these nanoparticles, this study fully elucidates their composition and core@shell structure. State-of-the-art electron microscopy and statistical data processing enabled chemical mapping of individual particles through the acquisition of energy-filtered transmission electron microscopy (EFTEM) images and detailed electron energy loss spectroscopy (EELS) analysis. Multivariate statistical analysis (MSA) has been used to greatly improve the quality of elemental mapping data from core@shell nanoparticles. Results from a combination of spatially resolved microanalysis reveal the shell as Fe3O4 and show that the core is composed of oxidatively stable metallic Co. For the first time, a region of lower atom density between the particle core and shell has been observed and identified as a trapped carbon residue attributable to the organic capping agents present in the initial Co nanoparticle synthesis.


Racial Disparities in Associations between Neighborhood Demographic Polarization and Birth Weight.
Neighborhood demographic polarization, or the extent to which a privileged population group outnumbers a deprived group, can affect health by influencing social dynamics. While using birth records from 2001 to 2013 in Massachusetts (n = 629,675), we estimated the effect of two demographic indices, racial residential polarization (RRP) and economic residential polarization (ERP), on birth weight outcomes, which are established predictors of the newborn's future morbidity and mortality risk. Higher RRP and ERP was each associated with higher continuous birth weight and lower odds for low birth weight and small for gestational age, with evidence for effect modification by maternal race. On average, per interquartile range increase in RRP, the birth weight was 10.0 g (95% confidence interval: 8.0, 12.0) higher among babies born to white mothers versus 6.9 g (95% CI: 4.8, 9.0) higher among those born to black mothers. For ERP, it was 18.6 g (95% CI: 15.7, 21.5) higher among those that were born to white mothers versus 1.8 g (95% CI: -4.2, 7.8) higher among those born to black mothers. Racial and economic polarization towards more privileged groups was associated with healthier birth weight outcomes, with greater estimated effects in babies that were born to white mothers than those born to black mothers.


The echinococcoses in Asia: The present situation.
Human alveolar and cystic echinococcosis, caused by the accidental ingestion of eggs of the tapeworms Echinococcus multilocularis and Echinococcus granulosus sensu lato, respectively, are endemic in Asia. Various Echinococcus species are maintained in domesticated and/or wild mammals through predator-prey interactions. Molecular analysis is used to help differentiate infecting parasite species and genotypes, with the goal of better understanding parasite life cycles in order to aid in the planning and implementation of control programs. This paper discusses the various echinococcoses in Asia, with limited reference to neighboring areas, including parts of Central Asia, Russia, Europe and North America.


Isolation of bacteria from diabetic foot ulcers with special reference to anaerobe isolation by simple two-step combustion technique in candle jar.
Although polymicrobial infections involving both aerobic and anaerobic bacteria are very common in diabetic foot ulcers, in many centres of developing countries, anaerobes are rarely isolated due to technical difficulties. This can be overcome by using a new simple, innovative technique of a combination of candle combustion and use of acidified copper-coated steel wool, as reported here. In-house developed method was used in a prospective clinico-microbiological study for anaerobes from randomly selected 43 patients with diabetic foot ulcers along with conventional method of anaerobic culture in GasPak system and aerobic culture by standard laboratory procedures. For primary isolation of anaerobes, Brucella blood agar supplemented with hemin (5 μg/ml) and menadione (1 μg/ml) was used. Antibiotic sensitivity tests were performed by the standard disc diffusion method for aerobes and E-test method for anaerobes. All the 43 samples were culture positive, of which aerobic Gram-negative bacteria (GNB) predominated, followed by Staphylococcus aureus, Enterococcus and diphtheroids. Anaerobes isolated from 21 samples were Peptostreptococcus, Bacteroides, Porphyromonas, Veillonella spp. and Clostridium perfringens by both GasPak and in-house developed and modified candle jar techniques. Imipenem and metronidazole were most sensitive while clindamycin, penicillin and cefoxitin were least sensitive drugs for anaerobes. Aerobic GNB were found to be multidrug resistant, especially to penicillin and cephalosporins. The most sensitive drug was piperacillin-tazobactam. For isolation of anaerobes from clinical specimens such as diabetic foot ulcers, modified candle jar technique was found to be as reliable as GasPak system. This modified technique needs to be tested for many other clinical materials which are not yet evaluated.


Local anaesthetic activity of some new substituted acylamides II.
Six new substituted acylamides, chemically related to lignocaine were studied for local anaesthetic activity and toxicity in mice, frogs and guinea pigs. Only one of these compounds, w-pyrrolidino 2, 3, 5, 6 tetramethyl acetanilide was found to possess potency comparable to lignocaine with a slightly higher therapeutic index. Study of the S.A.R. of this group indicated that by removal of two methyl groups at position 3 and 5 in the above compound, a local anaesthetic with greater potency than lignocaine may be obtained. Further exploration of the potentialities of a compound having pyrrolidine group as a part of basic side chain is indicated.


Expression of ameloblastin during enamel formation in a crocodile.
Ameloblastin is an enamel-specific protein that plays critical roles in enamel formation, as well as adhesion between ameloblasts and the enamel matrix, as shown by analyses of ameloblastin-null mice. In the present study, we produced two distinct antibodies that recognize the N-terminus and C-terminus regions of caiman ameloblastin, in order to elucidate the fate of ameloblastin peptides during tooth development. An immunohistochemical study using the antibodies showed that caiman ameloblastin was a tooth-specific matrix protein that may initially be cleaved into two groups, N- and C-terminal peptides, as shown in mammals. The distribution of the N-terminal peptides was much different from that of the C-terminal peptides during enamel formation; however, it was similar to that of mammalian ameloblastin. Although ameloblastin is thought to have a relationship with the enamel prismatic structure in mammals, in the caiman, which has non-prismatic enamel, functional ameloblastin has no relationship with any enamel structure. Consequently, it is suggested that ameloblastin has kept its original functions during the evolutionary transition from reptiles to mammals and that it has been conserved in both lineages during more than 200 million years of evolution. Our results support the notion that ameloblastin acts as a factor for ameloblast adhesion to enamel matrix, because distribution of the C-terminal peptides was consistently restricted on the surface layers of enamel matrix specimens ranging from immature to nearly completely mature. The principal molecules that provide the adhesive function are presumably C-terminal peptides.


Unexplained syncope.
There is a large patient population that experiences syncope. Although the exact mechanism is not known, arrhythmias and vasodepressor mechanisms probably account for most cases of unexplained syncope. Fortunately, patients with unexplained syncope can be successfully treated once the correct diagnosis has been established.


Evolution of cooperation under a generalized death-birth process.
According to the evolutionary death-birth protocol, a player is chosen randomly to die and neighbors compete for the available position proportional to their fitness. Hence, the status of the focal player is completely ignored and has no impact on the strategy update. In this paper, we revisit and generalize this rule by introducing a weight factor to compare the payoff values of the focal and invading neighbors. By means of evolutionary graph theory, we analyze the model on joint transitive graphs to explore the possible consequences of the presence of a weight factor. We find that focal weight always hinders cooperation under weak selection strength. Surprisingly, the results show a nontrivial tipping point of the weight factor where the threshold of cooperation success shifts from positive to negative infinity. Once focal weight exceeds this tipping point, cooperation becomes unreachable. Our theoretical predictions are confirmed by Monte Carlo simulations on a square lattice of different sizes. We also verify the robustness of the conclusions to arbitrary two-player prisoner's dilemmas, to dispersal graphs with arbitrary edge weights, and to interaction and dispersal graphs overlapping arbitrarily.


Activation and Stabilization of Lipase B from Candida antarctica by Immobilization on Polymer Brushes with Optimized Surface Structure.
A reusable support system for the immobilization of lipases is developed using hybrid polymer-inorganic core shell nanoparticles. The biocatalyst core consists of a silica nanoparticle. PMMA is grafted from the nanoparticle as polymer brush via ARGET ATRP (activator regenerated by electron transfer atom transfer radical polymerization), which allows defining the surface properties by chemical synthesis conditions. Lipase B from Candida antarctica is immobilized on the hybrid particles. The activity and stability of the biocatalyst are analyzed by spectroscopic activity analysis. It is shown that the hydrophobic PMMA brushes provide an activating surface for the lipase giving a higher specific activity than the enzyme in solution. Varying the surface structure from disordered to ordered polymer brushes reveals that the reusability of the biocatalyst is more effectively optimized by the surface structure than by the introduction of crosslinking with glutaraldehyde (GDA). The developed immobilization system is highly suitable for biocatalysis in non-native media which is shown by a transesterification assay in isopropyl alcohol and an esterification reaction in n-heptane.


Evaluating survival model performance: a graphical approach.
In the last decade, many statistics have been suggested to evaluate the performance of survival models. These statistics evaluate the overall performance of a model ignoring possible variability in performance over time. Using an extension of measures used in binary regression, we propose a graphical method to depict the performance of a survival model over time. The method provides estimates of performance at specific time points and can be used as an informal test for detecting time varying effects of covariates in the Cox model framework. The method is illustrated on real and simulated data using Cox proportional hazard model and rank statistics.


A Real-Life Study of Combined Treatment with Long-Term Non-Invasive Ventilation and High Flow Nasal Cannula in Patients with End-Stage Chronic Obstructive Lung Disease.
Patients with end-stage chronic obstructive pulmonary disease (COPD) often develop persistent hypoxic or hypercapnic respiratory failure, or a combination of both. Ventilatory support, in terms of a long-term high-flow nasal cannula (LT-HFNC) and long-term non-invasive ventilation (LT-NIV), may be indicated. Often, clinicians choose either one or the other. This paper explores combined treatment with LT-HFNC and LT-NIV in a real-life setting. In total, 33 patients with COPD and persistent respiratory failure were included in this study. Of those, 17 were initiated on LT-HFNC and used it for 595 (374) days and 16 were initiated on LT-NIV and used it for 558 (479) days. On average, patients used respiratory support continuously for 908 (586) days. Baseline characteristics were comparable, apart from PaCO2 at first ventilatory support initiation (LT-HFNC/LT-NIV 7.1 (1.1) kPa/8.8 (0.9) kPa respectively (p = 0.002)). Both groups experienced a reduction in hospitalizations in the first twelve months after treatment initiation, compared to the twelve months before (LT-HFNC p = 0.022 and LT-NIV p = 0.014). In total, 25% of LT-NIV patients stopped treatment after HFNC initiation due to intolerance and 59% stopped LT-HFNC treatment 126 (36) days after LT-NIV initiation as monotherapy was sufficient. In 44% of these patients, LT-HFNC was re-initiated at the end of life. At the time of analysis, 70% of patients had died. In the last three months of life, patients stopped using LT-NIV, whereas 91% used LT-HFNC. In conclusion, the combined use of LT-NIV and LT-HFNC reduced hospitalizations in patients with COPD and persistent respiratory failure. The study indicates that LT-HFNC is well tolerated, and better tolerated than LT-NIV at the very end stages of COPD.


New targeted therapies for breast cancer: A focus on tumor microenvironmental signals and chemoresistant breast cancers.
Breast cancer is the most frequent female malignancy worldwide. Current strategies in breast cancer therapy, including classical chemotherapy, hormone therapy, and targeted therapies, are usually associated with chemoresistance and serious adverse effects. Advances in our understanding of changes affecting the interactome in advanced and chemoresistant breast tumors have provided novel therapeutic targets, including, cyclin dependent kinases, mammalian target of rapamycin, Notch, Wnt and Shh. Inhibitors of these molecules recently entered clinical trials in mono- and combination therapy in metastatic and chemo-resistant breast cancers. Anticancer epigenetic drugs, mainly histone deacetylase inhibitors and DNA methyltransferase inhibitors, also entered clinical trials. Because of the complexity and heterogeneity of breast cancer, the future in therapy lies in the application of individualized tailored regimens. Emerging therapeutic targets and the implications for personalized-based therapy development in breast cancer are herein discussed.


Resting-state networks representation of the global phenomena.
Resting-state functional magnetic resonance imaging (rsfMRI) has been widely applied to investigate spontaneous neural activity, often based on its macroscopic organization that is termed resting-state networks (RSNs). Although the neurophysiological mechanisms underlying the RSN organization remain largely unknown, accumulating evidence points to a substantial contribution from the global signals to their structured synchronization. This study further explored the phenomenon by taking advantage of the inter- and intra-subject variations of the time delay and correlation coefficient of the signal timeseries in each region using the global mean signal as the reference signal. Consistent with the hypothesis based on the empirical and theoretical findings, the time lag and correlation, which have consistently been proven to represent local hemodynamic status, were shown to organize networks equivalent to RSNs. The results not only provide further evidence that the local hemodynamic status could be the direct source of the RSNs' spatial patterns but also explain how the regional variations in the hemodynamics, combined with the changes in the global events' power spectrum, lead to the observations. While the findings pose challenges to interpretations of rsfMRI studies, they further support the view that rsfMRI can offer detailed information related to global neurophysiological phenomena as well as local hemodynamics that would have great potential as biomarkers.


Glial scar-modulation as therapeutic tool in spinal cord injury in animal models.
Spinal Cord injury represents, in veterinary medicine, most of the neurological attendances and may result in permanent disability, death or euthanasia. Due to inflammation resulting from trauma, it originates the glial scar, which is a cell interaction complex system. Its function is to preserve the healthy circuits, however, it creates a physical and molecular barrier that prevents cell migration and restricts the neuroregeneration ability. This review aims to present innovations in the scene of treatment of spinal cord injury, approaching cell therapy, administration of enzyme, anti-inflammatory, and other active principles capable of modulating the inflammatory response, resulting in glial scar reduction and subsequent functional improvement of animals. Some innovative therapies as cell therapy, administration of enzymes, immunosuppressant or other drugs cause the modulation of inflammatory response proved to be a promising tool for the reduction of gliosis. Those tools promise to reduce gliosis and promote locomotor recovery in animals with spinal cord injury.


A validation study of a pain classification system for advanced cancer patients using content experts: the Edmonton Classification System for Cancer Pain.
The purpose of this study was to gather construct validity evidence for a pain classification system for advanced cancer patients using content experts. Two expert panels, representing regional (Panel A, n = 18) and national/international (Panel B, n = 52) palliative medicine and pain specialists, were purposefully selected to participate in a modified Delphi survey technique, to evaluate an existing pain classification system, the Revised Edmonton Staging System (rESS). Each panel participated in two survey rounds, with response rates of 67% (Panel A, Round 1), 39% (Panel A, Round 2), 56% (Panel B, Round 1) and 64% (Panel B, Round 2). The rESS consists of five features: mechanism of pain, incidental pain, psychological distress, addictive behavior and cognitive function. Most participants either agreed or strongly agreed with including the five existing rESS features in a pain classification system, ranging from 67% (Panel A, cognitive function) to 100% (Panel B, mechanism of pain). Most participants suggested keeping the current definitions for these features, with some revisions. Based on participant feedback, definitions for incidental pain, psychological distress, addictive behavior and cognitive function were revised, including the development of guidelines for use. To reflect its intended use as a classification system, the name of the instrument was changed to the Edmonton Classification System for Cancer Pain (ECS-CP).


A Concept Analysis of Self-Silencing.
Self-silencing describes the phenomenon of "loss of voice." A clear and comprehensive definition of self-silencing is relevant for nursing research and practice to promote a better understanding of detrimental health outcomes that may result from self-silencing. This concept analysis used a modified version of Walker & Avant's method to identify attributes, antecedents, and consequences of self-silencing. Self-silencing has psychological and sociocultural dimensions that may result in negative health consequences. Directions for research, practice, and policy are included.


[Dynamic analysis of HBV cccDNA in HepG2 cells infected with Ad-1.2 HBV].
o study the replication of hepatitis B virus (HBV) in HepG2 cells infected with Ad-1.2 HBV. HepG2 cells were transfected with adenovirus containing 1.2 copies of HBV DNA. The expression of HBV antigens were detected in the culture medium by means of enzyme-linked immunosorbent assay (ELISA), and the covalently closed circular DNA (cccDNA) in the cells was extracted with plasmid extraction kit and detected by real-time PCR with selective primer after treatment with mung bean nuclease. HBsAg, HBeAg and HBV cccDNA were all detected in HepG2 cells after tranfection with Ad-1.2 HBV. HBV cccDNA was detected 1 day after the infection, reaching the peak level 4 days after infection. Ad-1.2 HBV-infected cells can serve as the model for screening and evaluation of antiviral agents.


The usefulness of 4-amino-3-hydroxyphenylalanine as a specific marker of pheomelanin.
Reductive hydrolysis of pheomelanin with hydriodic acid (HI) gives two aminohydroxyphenylalanine isomers, 4-amino-3-hydroxyphenylalanine ('specific AHP') and 3-amino-4-hydroxyphenylalanine (3-aminotyrosine, AT), which derive from the oxidative polymerization of 5-S-cysteinyldopa, and 2-S-cysteinyldopa, respectively. Since we first introduced this analytical method, the combined amount of AHP and AT ('total AHP') has been extensively used as a marker of pheomelanin. However, one problem with using total AHP as a marker is that background levels originate from precursors other than pheomelanin. Considerable and variable amounts of background AT are produced from other sources, most likely nitrotyrosine residues in proteins. In order to overcome this problem, we developed HPLC conditions which enable the direct injection of the HI reduction products into the HPLC system allowing good separation of AHP and AT. In this way we could study the importance of both degradation products separately and their specificity as markers for pheomelanin. The usefulness of the present method is validated using human hair samples of various colours which were divided into dark, fair or red colours. The combined amount of specific AHP and AT shows an excellent correlation with total AHP, and the amount of specific AHP also correlates with the amount of total AHP. We also examined total AHP and specific AHP values against pyrrole-2,3,5-tricarboxylic acid (PTCA) values in the human hair samples. These results show that specific AHP measurement gives a more prominent segregation for the ratio of specific AHP to PTCA among hairs of various colours than the ratio of total AHP to PTCA. Thus, we conclude that 'specific AHP' is a more specific marker of pheomelanin than is 'total AHP'.


EBF recommendation on the validation of bioanalytical methods for dried blood spots.
Over the last few years bioanalysts, pharmacokineticists and clinical investigators have rediscovered the technique of dried blood spots. The revival has provided pharmaceutical R&D a wealth of opportunities to optimize the drug-discovery and development process with respect to animal and patient ethics, new scientific insights and costs savings. On the bioanalytical front, multiple experiments have been performed and a lot of experience has been gained. Nevertheless, the technique still has a number of bioanalytical challenges. The European Bioanalysis Forum discussed the advantages and hurdles of the technique and summarized their current thinking in a recommendation on the validation of bioanalytical methods for dried blood spots, which can be used as a cornerstone for further discussions and experiments.


Cortical thickness alterations are associated with astrocytes and excitatory neuron-specific transcriptome signatures in pediatric bipolar disorder.
Bipolar disorder (BD) is a heritable psychiatric disorder with a complex etiology that is often associated with cortical alterations. Morphometric studies in adults with BD are well established; however, few have examined cortical changes in pediatric BD (PBD). Additionally, the correlation between cortical thickness (CT) changes in PBD and gene expression remains elusive. Here, we performed an integrative analysis using neuroimaging data from 58 PBD individuals and the Allen human brain transcriptomic dataset. We applied partial least squares (PLS) regression analysis on structural MRI data and cortical gene expression, enrichment and specific cell type analysis to investigate the genetic correlates of CT alterations in PBD. We found the expression levels of PBD-related genes showed significant spatial correlations with CT differences. Further enrichment and specific cell type analysis revealed that transcriptome signatures associated with cortical thinning were enriched in synaptic signaling, ion channels, astrocytes, and excitatory neurons. Neurodevelopmental patterns of these genes showed significantly increased expression in the cerebellum, cortex, and subcortical regions during the adolescence period. These results highlight neurodevelopmental transcriptional changes could account for most of the observed correlations with CT differences in PBD, which offers a novel perspective to understand biological conceptualization mechanisms for the genetic correlates of CT alterations.


Integrated Multi-Omics Analysis of Mechanisms Underlying Yeast Ethanol Tolerance.
For yeast cells, tolerance to high levels of ethanol is vital both in their natural environment and in industrially relevant conditions. We recently genotyped experimentally evolved yeast strains adapted to high levels of ethanol and identified mutations linked to ethanol tolerance. In this study, by integrating genomic sequencing data with quantitative proteomics profiles from six evolved strains (data set identifier PXD006631) and construction of protein interaction networks, we elucidate exactly how the genotype and phenotype are related at the molecular level. Our multi-omics approach points to the rewiring of numerous metabolic pathways affected by genomic and proteomic level changes, from energy-producing and lipid pathways to differential regulation of transposons and proteins involved in cell cycle progression. One of the key differences is found in the energy-producing metabolism, where the ancestral yeast strain responds to ethanol by switching to respiration and employing the mitochondrial electron transport chain. In contrast, the ethanol-adapted strains appear to have returned back to energy production mainly via glycolysis and ethanol fermentation, as supported by genomic and proteomic level changes. This work is relevant for synthetic biology where systems need to function under stressful conditions, as well as for industry and in cancer biology, where it is important to understand how the genotype relates to the phenotype.


The manifestation of systemic vasculitis in the central nervous system--a case report.
We present a case of a patient with systemic vasculitis suffering--besides heart, skin and gastrointestinal lesions--from the rarely reported involvement of the central nervous system. Even though the diagnosis could not be ascertained precisely, immunosuppressive therapy led to prompt regression of symptoms including initially present neurologic manifestations.


Use of a handheld Doppler to measure brachial and femoral artery occlusion pressure.
Objective: Measurement of arterial occlusion pressure (AOP) is essential to the safe and effective use of blood flow restriction during exercise. Use of a Doppler ultrasound (US) is the "gold standard" method to measure AOP. Validation of a handheld Doppler (HHDOP) device to measure AOP could make the measurement of AOP more accessible to practitioners in the field. The purpose of this study was to determine the accuracy of AOP measurements of the brachial and femoral arteries using an HHDOP. Methods: We simultaneously measured AOP using a "gold standard" US and a HHDOP in the dominant and non-dominant arms (15 males; 15 females) and legs (15 males; 15 females). Results: There were no differences in limb circumference or limb volume in the dominant and non-dominant arms and legs between males and females or between the dominant and non-dominant arms and legs of males and females. The differences between US and HHDOP measures of AOP in the dominant and non-dominant arms and legs were either not significant or small (<10 mmHg) and of little practical importance. There were no sex differences in AOP measurements of the femoral artery (p > 0.60). Bland-Altman analysis yielded an average bias (-0.65 mmHg; -2.93 mmHg) and reasonable limits of agreement (±5.56 mmHg; ±5.58 mmHg) between US and HHDOP measures of brachial and femoral artery AOP, respectively. Conclusion: HHDOP yielded acceptable measures of AOP of the brachial and femoral arteries and can be used to measure AOP by practitioners for the safe and effective use of blood flow restriction. Due to the potential differences in AOP between dominant and non-dominant limbs, AOP should be measured in each limb.


TransCrack: revisiting fine-grained road crack detection with a transformer design.
Prior convolution-based road crack detectors typically learn more abstract visual representation with increasing receptive field via an encoder-decoder architecture. Despite the promising accuracy, progressive spatial resolution reduction causes semantic feature blurring, leading to coarse and incontiguous distress detection. To these ends, an alternative sequence-to-sequence perspective with a transformer network termed TransCrack is introduced for road crack detection. Specifically, an image is decomposed into a grid of fixed-size crack patches, which is flattened with position embedding into a sequence. We further propose a pure transformer-based encoder with multi-head reduced self-attention modules and feed-forward networks for explicitly modelling long-range dependencies from the sequential input in a global receptive field. More importantly, a simple decoder with cross-layer aggregation architecture is developed to incorporate global with local attentions across different regions for detailed feature recovery and pixel-wise crack mask prediction. Empirical studies are conducted on three publicly available damage detection benchmarks. The proposed TransCrack achieves a state-of-the-art performance over all counterparts by a substantialmargin, and qualitative results further demonstrate its superiority in contiguous crack recognition and fine-grained profile extraction. This article is part of the theme issue 'Artificial intelligence in failure analysis of transportation infrastructure and materials'.


Two separate dose-dependent effects of paroxetine: mydriasis and inhibition of tramadol's O-demethylation via CYP2D6.
To investigate paroxetine's putative dose-dependent impact on pupil reaction and inhibition of the O-demethylation of tramadol. Twelve healthy CYP2D6 extensive metabolizers participated in this double-blinded randomized five-way placebo controlled cross-over study; they received placebo, 10, 20, 30, and 50 mg paroxetine as single oral doses at bedtime. Next morning the pupil was measured followed by oral intake of 50 mg of tramadol, and urine was collected for 8 h. Three hours after ingestion of tramadol a second measurement of the pupil was performed. Enantioselective urine concentrations of (+/-)-tramadol and (+/-)-O-desmethyltramadol (M1) were determined. With placebo, the median maximum pupil diameter was 6.43 mm (range 5.45-7.75 mm) before tramadol and 6.22 mm (4.35-7.65 mm) after 50 mg of tramadol (P = 0.4935). Paroxetine resulted in a statistically significant, dose-dependent dilatation of the pupil with a geometric mean difference of 1.17 (95% CI 1.10-1.24) after ingestion of 50 mg paroxetine (P < 0.001). Likewise, a reduction in the relative constriction amplitude with a geometric mean difference of 0.81 (95% CI 0.71-0.92) (P < 0.001) was seen. A dose-dependent inhibition of the metabolism of tramadol by an increase in the two urinary metabolic ratios (+)-tramadol / (+)-M1 [geometric mean difference 9.09, 95% CI 5.60-14.73 (P < 0.001)] and (-)-M1 / (+)-M1 [geometric mean difference 2.84, 95% CI 2.15-3.77 (P < 0.001)] was also observed. Paroxetine is a dose-dependent dilator of the pupil and as expected a dose-dependent inhibitor of (+)-tramadol's O-demethylation.


Polymerase chain reaction for detection of endocervical Chlamydia trachomatis infection in women attending a gynecology outpatient department in India.
To detect Chlamydia trachomatis infection by polymerase chain reaction (PCR) in symptomatic women attending a gynecology clinic in a city hospital and in randomly selected slum dwellers. Endocervical specimens were collected from 350 women with genitourinary complaints (group I) and 53 slum dwellers (group II). Samples were analyzed by PCR, direct fluorescence assay (DFA) and Giemsa stain cytology for detection of C trachomatis and compared for their sensitivity, specificity, positive predictive value (PPV) and negative predictive value (NPV). The prevalence of endocervical C trachomatis infection was 43.1% and 24.5% in groups I and II, respectively. The sensitivity, specificity, PPV and NPV of PCR were 80.0%, 75.0%, 66.6% and 85.7%, respectively, when DFA was considered true positive. The percent increment in detection of C trachomatis by PCR was 15.3%. Giemsa stain cytology has low sensitivity and specificity; hence, it cannot be recommended for use as a diagnostic technique. It appears that PCR can be used routinely in Chlamydia diagnosis and in screening selected populations. The high positivity of C trachomatis infection in urban slum dwellers is cause for concern.


Model-Free Prediction of Large Spatiotemporally Chaotic Systems from Data: A Reservoir Computing Approach.
We demonstrate the effectiveness of using machine learning for model-free prediction of spatiotemporally chaotic systems of arbitrarily large spatial extent and attractor dimension purely from observations of the system's past evolution. We present a parallel scheme with an example implementation based on the reservoir computing paradigm and demonstrate the scalability of our scheme using the Kuramoto-Sivashinsky equation as an example of a spatiotemporally chaotic system.


Effects of lobus parolfactorius lesions on repeated acquisition of spatial discrimination in pigeons.
The basal part of the avian telencephalon can be divided into the paleostriatum augmentatum, paleostriatum primitivum and lobus parolfactorius (LPO). In the present experiments, the cognitive functions of the LPO in pigeons were examined. Pigeons were trained on spatial discrimination with or without added color cues using a repeated acquisition procedure. The discrimination task was a choice of three keys in an operant chamber. Every time the subjects reached the criterion, they were trained on a different discrimination in which one of two previously incorrect keys became the correct key. In the task with added color each key had a unique color (i.e., color discrimination). The LPO lesions disrupted the acquisition of both the spatial discrimination and the discrimination with added color. Birds with LPO damage emitted many errors in the first trial indicating the preservation of a previously correct response. Thus, the LPO lesions caused cognitive rigidity. These results are consistent with clinical observations of patients with basal ganglia disorders.


The structural basis of chain length control in Rv1086.
In Mycobacterium tuberculosis, two related Z-prenyl diphosphate synthases, E,Z-farnesyl diphosphate synthase (Rv1086) and decaprenyl diphosphate synthase (Rv2361c), work in series to synthesize decaprenyl phosphate (C(50)) from isopentenyl diphosphate and E-geranyl diphosphate. Decaprenyl phosphate plays a central role in the biosynthesis of essential mycobacterial cell wall components, such as the mycolyl-arabinogalactan-peptidoglycan complex and lipoarabinomannan; thus, its synthesis has attracted considerable interest as a potential therapeutic target. Rv1086 is a unique prenyl diphosphate synthase in that it adds only one isoprene unit to geranyl diphosphate, generating the 15-carbon product (E,Z-farnesyl diphosphate). Rv2361c then adds a further seven isoprene units to E,Z-farnesyl diphosphate in a processive manner to generate the 50-carbon prenyl diphosphate, which is then dephosphorylated to generate a carrier for activated sugars. The molecular basis for chain-length discrimination by Rv1086 during synthesis is unknown. We also report the structure of apo Rv1086 with citronellyl diphosphate bound and with the product mimic E,E-farnesyl diphosphate bound. We report the structures of Rv2361c in the apo form, with isopentenyl diphosphate bound and with a substrate analogue, citronellyl diphosphate. The structures confirm the enzymes are very closely related. Detailed comparison reveals structural differences that account for chain-length control in Rv1086. We have tested this hypothesis and have identified a double mutant of Rv1086 that makes a range of longer lipid chains.