Altered neuroendocrine control and association to clinical symptoms in adolescent chronic fatigue syndrome: a cross-sectional study.
Chronic fatigue syndrome (CFS) is a common and disabling disorder, and a major threat against adolescent health. The pathophysiology is unknown, but alteration of neuroendocrine control systems might be a central element, resulting in attenuation of the hypothalamus-pituitary-adrenalin (HPA) axis and enhancement of the sympathetic/adrenal medulla (SAM) system. This study explored differences in neuroendocrine control mechanisms between adolescent CFS patients and healthy controls, and whether characteristics of the control mechanisms are associated with important clinical variables within the CFS group. CFS patients 12-18 years of age were recruited nation-wide to a single referral center as part of the NorCAPITAL project. A broad case definition of CFS was applied. A comparable group of healthy controls were recruited from local schools. A total of nine hormones were assayed and subjected to network analyses using the ARACNE algorithm. Symptoms were charted by a questionnaire, and daily physical activity was recorded by an accelerometer. A total of 120 CFS patients and 68 healthy controls were included. CFS patients had significantly higher levels of plasma norepinephrine, plasma epinephrine and plasma FT4, and significantly lower levels of urine cortisol/creatinine ratio. Subgrouping according to other case definitions as well as adjusting for confounding factors did not alter the results. Multivariate linear regression models as well as network analyses revealed different interrelations between hormones of the HPA axis, the SAM system, and the thyroid system in CFS patients and healthy controls. Also, single hormone degree centrality was associated with clinical markers within the CFS group. This study reveals different interrelation between hormones of the HPA axis, the SAM system, and the thyroid system in CFS patients and healthy controls, and an association between hormone control characteristics and important clinical variables in the CFS group. These results add to the growing insight of CFS disease mechanisms. Trial registration Clinical Trials NCT01040429.


The role of plant cell wall encapsulation and porosity in regulating lipolysis during the digestion of almond seeds.
Previous studies have provided evidence that the physical encapsulation of intracellular nutrients by cell walls of plant foods (i.e. dietary fibre) plays a predominant role in influencing macronutrient bioaccessibility (release) from plant foods during human digestion. One unexplored aspect of this is the extent to which digestive enzymes can pass through the cell-wall barrier and hydrolyse the intracellular lipid in almond seeds. The purpose of the present study was to assess the role played by cell walls in influencing the bioaccessibility and digestibility of almond lipid using a range of techniques. Digestibility experiments were performed on raw and roasted almond cells as well as isolated almond oil bodies using in vitro gastric and duodenal digestion models. Residual triacylglycerols and lipolysis products were extracted after 1 h of incubation and analysed by thin layer chromatography. The lipolysis kinetics of almond cells and oil bodies were also investigated using the pH-stat technique. Finally, the potential penetration of pancreatic lipase through the cell wall matrix was investigated using confocal microscopy. Differences in the rates and extent of lipolysis were clearly seen between almond cells and oil bodies, and these differences were observed regardless of the lipase(s) used. These results also showed that almond cell walls that are completely intact limit lipid digestibility, due to an encapsulation mechanism that hinders the diffusion of lipase into the intracellular environment and lipolysis products out of the cells.


Late swing or early stance? A narrative review of hamstring injury mechanisms during high-speed running.
Hamstring injuries are highly prevalent in many running-based sports, and predominantly affect the long head of biceps femoris. Re-injury rates are also high and together lead to considerable time lost from sport. However, the mechanisms for hamstring injury during high-speed running are still not fully understood. Therefore, the aim of this review was to summarize the current literature describing hamstring musculotendon mechanics and electromyography activity during high-speed running, and how they may relate to injury risk. The large eccentric contraction, characterized by peak musculotendon strain and negative work during late swing phase is widely suggested to be potentially injurious. However, it is also argued that high hamstring loads resulting from large joint torques and ground reaction forces during early stance may cause injury. While direct evidence is still lacking, the majority of the literature suggests that the most likely timing of injury is the late swing phase. Future research should aim to prospectively examine the relationship between hamstring musculotendon dynamics and hamstring injury.


Genetic polymorphisms in the osteopontin promoter increases the risk of distance metastasis and death in Chinese patients with gastric cancer.
In vitro and in vivo studies have suggested that osteopontin (OPN) is associated with many types of cancers. However, no studies have reported the incidence of OPN polymorphisms and the risk of gastric cancer. The aim of this study was to investigate the association between OPN polymorphisms and gastric cancer in a Chinese patient population. Three genetic variants in the OPN promoter were genotyped using direct sequencing in 200 gastric cancer patients and 200 gender- and age-matched cancer-free controls. The 4-year survival curve was calculated using the Kaplan-Meier method and compared using the log-rank test for each single nucleotide polymorphism (SNP) site. We measured the promoter activity of the -443 T → C polymorphism using a dual luciferase reporter assay. For the variant at nt -443 (CC), there was a significant difference between the number of patients with stage IV and those with stage I gastric cancer (IA + IB; P = 0.014) and between those with stage IV and all other stages of gastric cancer (IA + IB + II + III; P = 0.02). For the variant at nt -443 (CT), there was a significant difference between the number of gastric cancer patients with stage IV and those with stage II (P = 0.013). The survival rates for patients with the C/C genotype were significantly lower than for patients with the other two genotypes (C/T, T/T). Moreover, significantly higher luciferase activities were observed in the pGL3-C construct compared to the pGL3-T construct. This study provides the first evidence that variation at nt -443 in the OPN promoter increases the potential for gastric cancer metastasis and subsequent death in the Chinese population.


Differences in Phyllotreta cruciferae and Phyllotreta striolata (Coleoptera: Chrysomelidae) responses to neonicotinoid seed treatments.
Insecticidal seed treatments are used commonly throughout the Northern Great Plains of North America to systemically protect seedlings of canola (Brassica napus L. and Brassica rapa L.) from attack by the flea beetles Phyllotreta cruciferae (Goeze) and Phyllotreta striolata (F.) (Coleoptera: Chrysomelidae). Here, we investigated differential responses by the two flea beetle species to the neonicotinoid seed treatments thiamethoxam (Helix and Helix XTra) and clothianidin (Prosper 400) in greenhouse experiments. P. cruciferae experienced higher mortality and fed less when exposed to these compounds than did P. striolata. Beetles of the overwintered and the summer generations responded differently when feeding on seedlings that developed with insecticidal seed treatments, with mortality higher for P. cruciferae in May than in August. When the two flea beetle species were held together at equal densities and allowed to feed on seedlings affected by the seed treatments, mortality of P. cruciferae significantly exceeded that of P. striolata. Differences in efficacies of these compounds for these beetles have ramifications for management strategies in regions where these insects occur sympatrically. Competitive release of P. striolata was previously reported to occur when P. cruciferae was excluded from brassicaceous crops; consequently, the consistent use of these seed treatments over millions of hectares of canola cropland may be a factor that contributes to a shift in prevalence of flea beetle pest species from P. cruciferae toward P. striolata.


Implementing a mobile diagnostic unit to increase access to imaging and laboratory services in western Kenya.
Access to basic imaging and laboratory services remains a major challenge in rural, resource-limited settings in sub-Saharan Africa. In 2016, the Academic Model Providing Access to Healthcare programme in western Kenya implemented a mobile diagnostic unit (MDU) outfitted with a generator-powered X-ray machine and basic laboratory tests to address the lack of these services at rural, low-resource, public health facilities. The objective of this paper is to describe the design, implementation, preliminary impact and operational challenges of the MDU in western Kenya. Since implementing the MDU at seven rural health facilities serving a catchment of over half a million people, over 4500 chest radiographs have been performed, with one or more abnormalities detected in approximately 30% of radiographs. We observed favorable feedback and uptake of MDU services by healthcare workers and patients. However, various operational challenges in the design and construction of the MDU and the transmission and reporting of radiographs in remote areas were encountered. Our experience supports the feasibility of deploying an MDU to increase access to basic radiology and laboratory services in rural, resource-limited settings.


iRhom2-mediated proinflammatory signalling regulates heart repair following myocardial infarction.
The role of proinflammation, and specifically TNF-α, on downstream fibrosis and healing after cardiac injury remains unknown. Using iRhom2-deficient mice, which lack myeloid-specific shedding of TNF-α, we reveal increased macrophages (MΦs) that were skewed towards a more proinflammatory (M1) state at day 4, followed by more reparative, antiinflammatory (M2) state at day 7 after myocardial infarction (MI). However, associated functional cytokine expression was significantly reduced in iRhom2-mutant M1 and M2 MΦs, respectively. A dampened proinflammatory signature in iRhom2-deficient mice during the acute phase of injury and subsequent changes in MΦ polarization were associated with reduced phagocytosis and a more sparse distribution within the scar region. This resulted in impaired collagen deposition and fibrosis, and increased left ventricular remodelling and mortality in iRhom2-deficient mice after MI. Our findings reveal a requirement for an iRhom2-mediated proinflammatory response during downstream scarring and fibrosis, which is driven in part by TNF-α signaling. These conclusions challenge the existing model that infarct repair is determined exclusively by antiinflammatory signaling of M2 MΦs, and as such we propose an alternative view of immunomodulation to maintain effective healing after infarction.


Assembly of g-C3N4-based type II and Z-scheme heterojunction anodes with improved charge separation for photoelectrojunction water oxidation.
Graphitic carbon nitride (g-C3N4) has been widely studied as a metal-free photocatalyst, leading to some excellent results; however, the rapid recombination of photogenerated charge carriers substantially limits its performance. Here, we establish two types of g-C3N4-based heterojunction (type II and nonmediator assisted Z-scheme) photoanodes on a transparent conducting substrate via coupling with rod-like and nanoparticulate WO3, respectively. In these composites, g-C3N4 film grown by electrophoretic deposition of exfoliated g-C3N4 serves as the host or guest material. The optimized type II WO3/g-C3N4 composite exhibits an enhanced photocurrent of 0.82 mA cm-2 at 1.23 V vs. RHE and an incident photo-to-current conversion efficiency (IPCE) of 33% as compared with pure WO3 nanorods (0.22 mA cm-2 for photocurrent and 15% for IPCE). Relative to pure g-C3N4 film (with a photocurrent of several microampere and an IPCE of 2%), a largely improved photocurrent of 0.22 mA cm-2 and an IPCE of 20% were acquired for the Z-scheme g-C3N4/WO3 composite. The enhancement can be attributed to accelerated charge separation in the heterointerface because of the suitably aligned band gap between WO3 and g-C3N4, as confirmed by optical spectroscopy and ultraviolet photoelectron spectroscopy (UPS) analysis. The photocatalytic process and mechanism of the g-C3N4-based heterojunctions are proposed herein, which potentially explain the origin of the enhanced photoelectrochemical performance. This achievement and the fundamental information supplied here indicate the importance of rationally designing heterojunction photoelectrodes to improve the performance of semiconductors. This is particularly important for materials such as pure g-C3N4 and WO3, as their photoactivities are strongly restricted by high recombination rates.


MicroRNA profiling of human gastric cancer.
MicroRNAs are a group of small non-coding RNAs that modulate gene expression. The de-regulation of microRNA expression has been found in several types of cancer. To study the role of microRNAs in gastric cancer (GC), we analyzed the expression profile of 847 microRNAs in GC from Chinese patients. Total RNA was used for hybridization on the miRCURY LNA Array (v. 11.0), which contains probes specific for 847 human microRNAs. The results from the miRNA microarray analysis were validated by real-time RT-PCR. A total of 24 miRNAs with a more than 2-fold change were differentially expressed between normal gastric tissue and GC. Of these, 22 miRNAs (miR-223, miR-106b, miR-147, miR-34a, miR-130b*, miR-106a, miR-18a, miR-17, miR-98, miR-616*, miR-181a-2*, miR-185, miR-1259, miR-601, miR-196a*, miR-221*, miR-302f, miR-340*, miR-337-3p, miR-520c-3p, miR-575 and miR-138) were significantly up-regulated in GC (P<0.05), whereas only miR-638 and miR-378 were significantly down-regulated in GC (P<0.05) compared to normal gastric tissue. The expression of miR-185 and miR-638, as measured by miRNA microarray analysis, was in agreement with the expression level of these microRNAs found by real-time RT-PCR in the same samples. Our results show that microRNAs are de-regulated in GC, suggesting the involvement of these genes in the development and progression of gastric cancer.


Radionuclide based imaging of prostate cancer.
Prostate cancer (PCa) is the second leading cause of cancer deaths in American men. Early detection of PCa by blood tests for elevated levels of prostate-specific-antigen (PSA) has lead to early treatment and a reduction in death rates. However, PSA level alone does not distinguish between PCa and normal conditions that cause elevated PSA. Furthermore, because PCa can be a very slow growing cancer, even confirmation of PCa cells in a biopsy gives no indication whether the PCa will progress into active disease within the individual's lifetime. As a result many patients receive treatment that they may not need. Imaging is an attractive modality for the detection and characterization of disease because most techniques are non- or minimally invasive, nondestructive, provide dynamic real-time data, and allow for repeat measurements. In PCa, advanced imaging techniques could be useful for accurate staging of primary disease, restaging of recurrent disease, detection of metastatic lesions, and predicting the aggressiveness of the disease. This paper reviews the radionuclide based imaging agents for planar, single photon emission computed tomography (SPECT), and positron emission tomography (PET) imaging currently used in the clinic and those under development for PCa. The former includes the bone agents technetium diphosphonates and F-18 fluoride, the metabolic agents 2-[¹⁸F]fluoro-2-deoxy-D-glucose (FDG), and receptor targeted radiolabeled monoclonal antibodies including ProstaScint. The latter agents include C-11 acetate, C-11 and F-18 choline, C-11 and F-18 labeled 1-aminocyclobutane-1-carboxylic acid, radiolabeled androgen receptor binding compounds, radiolabeled peptides and small molecules for receptors over expressed either on prostate cancer itself or on the associated tumor neovasculature. Coregistration of PET or SPECT images with CT or MRI scans, improvements in imaging cameras, and image reconstruction algorithms have improved the quality of the images to the point where dual modality (radionuclide/CT or MRI) imaging with several agents can now be considered for staging of PCa. In addition, the high selectivity and rapid localization of many of the new agents under development portends promise for a greater use of radionuclide imaging for prostate cancer detection, characterization, and treatment monitoring.


The precise timeline of transcriptional regulation reveals causation in mouse somitogenesis network.
In vertebrate development, the segmental pattern of the body axis is established as somites, masses of mesoderm distributed along the two sides of the neural tube, are formed sequentially in the anterior-posterior axis. This mechanism depends on waves of gene expression associated with the Notch, Fgf and Wnt pathways. The underlying transcriptional regulation has been studied by whole-transcriptome mRNA profiling; however, interpretation of the results is limited by poor resolution, noisy data, small sample size and by the absence of a wall clock to assign exact time for recorded points. We present a method of Maximum Entropy deconvolution in both space and time and apply it to extract, from microarray timecourse data, the full spatiotemporal expression profiles of genes involved in mouse somitogenesis. For regulated genes, we have reconstructed the temporal profiles and determined the timing of expression peaks along the somite cycle to a single-minute resolution. Our results also indicate the presence of a new class of genes (including Raf1 and Hes7) with two peaks of activity in two distinct phases of the somite cycle. We demonstrate that the timeline of gene expression precisely reflects their functions in the biochemical pathways and the direction of causation in the regulatory networks. By applying a novel framework for data analysis, we have shown a striking correspondence between gene expression times and their interactions and regulations during somitogenesis. These results prove the key role of finely tuned transcriptional regulation in the process. The presented method can be readily applied to studying somite formation in other datasets and species, and to other spatiotemporal processes.


Distribution of polyunsaturated Fatty acids in bacteria present in intestines of deep-sea fish and shallow-sea poikilothermic animals.
The lipid and fatty acid compositions in nine obligate and facultative barophilic bacteria isolated from the intestinal contents of seven deep-sea fish were determined. Phospholipid compositions were simple, with phosphatidylethanolamine and phosphatidylglycerol predominating in all strains. Docosahexaenoic acid (DHA; 22:6n-3), which has not been reported in procaryotes except for deep-sea bacteria, was found to be present in eight strains at a level of 8.1 to 21.5% of total fatty acids. In the other strain, eicosapentaenoic acid (EPA; 20:5n-3) was present at a level of 31.5% of total fatty acids. Other fatty acids observed in all strains were typical of marine gram-negative bacteria. Subcultures from pouches prepared from intestinal contents of five deep-sea fish by the most-probable-number (MPN) method were analyzed for fatty acids, and all subcultures contained DHA and/or EPA. Accordingly, viable cell counts of bacteria containing DHA and EPA were estimated at a maximum of 1.3 x 10(sup8) and 2.4 x 10(sup8) cells per ml, respectively, and accounted for 14 and 30%, respectively, of the total cell counts in the intestinal contents of the deep-sea fish. In the case of 10 shallow-sea poikilothermic animals having bacterial populations of 1.1 x 10(sup6) to 1.9 x 10(sup9) CFU per ml in intestinal contents, no DHA was found in the 112 isolates examined, while production of EPA was found in 40 isolates from cold- and temperate-sea samples. These results suggest that DHA and EPA are involved in some adaptations of bacteria to low temperature and high pressure.


Crimean-Congo hemorrhagic fever: history, epidemiology, pathogenesis, clinical syndrome and genetic diversity.
Crimean-Congo hemorrhagic fever (CCHF) is the most important tick-borne viral disease of humans, causing sporadic cases or outbreaks of severe illness across a huge geographic area, from western China to the Middle East and southeastern Europe and throughout most of Africa. CCHFV is maintained in vertical and horizontal transmission cycles involving ixodid ticks and a variety of wild and domestic vertebrates, which do not show signs of illness. The virus circulates in a number of tick genera, but Hyalomma ticks are the principal source of human infection, probably because both immature and adult forms actively seek hosts for the blood meals required at each stage of maturation. CCHF occurs most frequently among agricultural workers following the bite of an infected tick, and to a lesser extent among slaughterhouse workers exposed to the blood and tissues of infected livestock and medical personnel through contact with the body fluids of infected patients. CCHFV is the most genetically diverse of the arboviruses, with nucleotide sequence differences among isolates ranging from 20% for the viral S segment to 31% for the M segment. Viruses with diverse sequences can be found within the same geographic area, while closely related viruses have been isolated in far distant regions, suggesting that widespread dispersion of CCHFV has occurred at times in the past, possibly by ticks carried on migratory birds or through the international livestock trade. Reassortment among genome segments during co-infection of ticks or vertebrates appears to have played an important role in generating diversity, and represents a potential future source of novel viruses. In this article, we first review current knowledge of CCHFV, summarizing its molecular biology, maintenance and transmission, epidemiology and geographic range. We also include an extensive discussion of CCHFV genetic diversity, including maps of the range of the virus with superimposed phylogenetic trees. We then review the features of CCHF, including the clinical syndrome, diagnosis, treatment, pathogenesis, vaccine development and laboratory animal models of CCHF. The paper ends with a discussion of the possible future geographic range of the virus. For the benefit of researchers, we include a Supplementary Table listing all published reports of CCHF cases and outbreaks in the English-language literature, plus some principal articles in other languages, with total case numbers, case fatality rates and all CCHFV strains on GenBank.


An adaptive mixed reality training system for stroke rehabilitation.
This paper presents a novel mixed reality rehabilitation system used to help improve the reaching movements of people who have hemiparesis from stroke. The system provides real-time, multimodal, customizable, and adaptive feedback generated from the movement patterns of the subject's affected arm and torso during reaching to grasp. The feedback is provided via innovative visual and musical forms that present a stimulating, enriched environment in which to train the subjects and promote multimodal sensory-motor integration. A pilot study was conducted to test the system function, adaptation protocol and its feasibility for stroke rehabilitation. Three chronic stroke survivors underwent training using our system for six 75-min sessions over two weeks. After this relatively short time, all three subjects showed significant improvements in the movement parameters that were targeted during training. Improvements included faster and smoother reaches, increased joint coordination and reduced compensatory use of the torso and shoulder. The system was accepted by the subjects and shows promise as a useful tool for physical and occupational therapists to enhance stroke rehabilitation.


Tregs facilitate obesity and insulin resistance via a Blimp-1/IL-10 axis.
Interleukin-10 (IL-10) is a critical cytokine used by immune cells to suppress inflammation. Paradoxically, immune cell-derived IL-10 can drive insulin resistance in obesity by suppressing adipocyte energy expenditure and thermogenesis. However, the source of IL-10 necessary for the suppression of adipocyte thermogenesis is unknown. We show here that CD4+Foxp3+ regulatory T cells (Tregs) are a substantial source of IL-10 and that Treg-derived IL-10 can suppress adipocyte beiging. Unexpectedly, Treg-specific loss of IL-10 resulted in increased insulin sensitivity and reduced obesity in high-fat diet-fed male mice. Mechanistically, we determined that Treg-specific loss of the transcription factor Blimp-1, a driver of IL-10 expression by Tregs, phenocopied the Treg-specific IL-10-deficient mice. Loss of Blimp-1 expression in Tregs resulted in reduced ST2+KLRG1+, IL-10-secreting Tregs, particularly in the white adipose tissue. Blimp-1-deficient mice were protected from glucose intolerance, insulin resistance, and diet-induced obesity, through increased white adipose tissue browning. Taken together, our data show that Blimp-1-regulated IL-10 secretion by Tregs represses white adipose tissue beiging to maintain adipose tissue homeostasis.


Interactions of Semliki Forest virus spike glycoprotein rosettes and vesicles with cultured cells.
Semliki Forest virus (SFV)-derived spike glycoprotein rosettes (soluble octameric complexes), virosomes (lipid vesicles with viral spike glycoproteins), and liposomes (protein-free lipid vesicles) have been used to investigate the interaction of subviral particles with BHK-21 cells. Cell surface binding, internalization, degradation, and low pH-dependent membrane fusion were quantitatively determined. Electron microscopy was used to visualize the interactions. Virosomes and rosettes, but not liposomes, bound to cells. Binding occurred preferentially to microvilli and was inhibited by added SFV; it increased with decreasing pH but was, in all cases, less efficient than intact virus. At 37 degrees C the cell surface-bound rosettes and virosomes were internalized via coated pits and coated vesicles. After a lag period of 45 min the protein components of the internalized ligands were degraded and appeared, as acid-soluble activity, in the medium. The uptake of rosettes and virosomes was found to be similar to the adsorptive endocytosis of SFV except that their average residence times on the cell surface were longer. The rosettes and the liposomes did not show low pH-induced membrane fusion activity. The virosomes, however, irrespective of the lipid compositions used, displayed hemolytic activity at mildly acidic pH and were able to fuse with the plasma membrane of cells with an efficiency of 0.25 that observed with intact viruses. Cell-cell fusion activity was not observed with any of the subviral components. The results indicated that subviral components possess some of the entry properties of the intact virus.


Influenza and pneumococcal vaccination in long term care facilities in two regions of Quebec.
To evaluate the use of influenza and pneumococcal vaccines in long term care facilities. Cross-sectional survey in a random sample of 30 facilities in two regions of Quebec. Information was collected from the general manager or the chief of nursing, all consultant physicians and a random sample of 20 residents in each facility. Twenty-nine centres agreed to participate. The mean influenza vaccination rate was 70%, and was not influenced by differences in the types of facilities or the organization of the programs for immunization. The main obstacle to influenza vaccination reported by physicians was nonacceptance by a significant proportion of residents. Of the residents who did not initially request influenza vaccine, only 64% accepted vaccination when it was offered. The vast majority of residents were satisfied with the information they had received and the respect shown for their freedom of choice. Forty per cent of residents were unfit to provide a valid consent and the vaccination rate was 76% in this group. Only one-third of the physicians regularly obtained authorization from a relative or the legal guardian before prescribing vaccination for incompetent residents. None of the facilities studied had an effective program for pneumococcal vaccination, only 43% of the physicians reported any use of pneumococcal vaccine and 98% of residents had never heard of the vaccine. The national objective of 95% coverage with influenza vaccine will be difficult to achieve in long term care facilities, mainly because a minority of residents are not likely to be convinced of the benefit of immunization. Much remains to be done to promote and administer pneumococcal vaccine in this setting.


Reporting and evaluation of HIV-related clinical endpoints in two multicenter international clinical trials.
The processes for reporting and review of progression of HIV disease clinical endpoints are described for two large phase III international clinical trials. SILCAAT and ESPRIT are multicenter randomized HIV trials evaluating the impact of interleukin-2 on disease progression and death in HIV-infected patients receiving antiretroviral therapy. We report definitions used for HIV progression of disease endpoints, procedures for site reporting of such events, processes for independent review of reported events by an Endpoint Review Committee (ERC), and the procedure for adjudication of differences of opinion between reviewers. Of 473 events reported through May 1, 2006, 28% were judged by an ERC to meet "confirmed" criteria and 38% to meet "probable" criteria; 34% were classified "does not meet criteria." For diseases with >5 case reports, the proportion accepted as either "confirmed" or "probable" events was highest for cervical cancer (100%), non-Hodgkin's lymphoma (88%), cryptococcosis (82%), and cryptosporidiosis (80%) and was lowest for HIV encephalopathy (25%), HIV wasting syndrome (33%), and multidermatomal herpes zoster (35%). 25% of cases required adjudication between reviewers before diagnostic certainty was assigned. Important requirements for HIV trials using clinical endpoints include objective definitions of "confirmed" and "probable," a formal reporting process with adequate information and supporting source documentation, evaluation by independent blinded reviewers, and procedures for adjudication.


Delivering Cognitive Behavioral Therapy for Post-Intensive Care Syndrome-Family via a Mobile Health App.
Family members of intensive care unit (ICU) patients are at risk for post-intensive care syndrome- family (PICS-F), including symptoms of anxiety, depression, and posttraumatic stress. Cognitive behavioral therapy is the first-line nonpharmacologic treatment for many psychological symptoms and has been successfully delivered by use of mobile technology for symptom self-management. To determine the feasibility of delivering cognitive behavioral therapy through a smartphone app to family members of critically ill patients. This was a prospective longitudinal cohort study with a consecutive sample of patients admitted to 2 adult ICUs and their family members. The control group period was followed by the intervention group period. The intervention consisted of a mobile health app preloaded on a smartphone provided to family members. The study time points were enrollment (within 5 days of ICU admission), 30 days after admission, and 60 days after admission. Study measures included demographic data, app use, satisfaction with the app, mental health self-efficacy, and measures of PICS-F symptoms. The study sample consisted of 49 predominantly White (92%) and female (82%) family members (24 intervention, 25 control). Smartphone ownership was 88%. Completion rates for study measures were 92% in the control group and 79% in the intervention group. Family members logged in to the app a mean of 18.58 times (range 2-89) and spent a mean of 81.29 minutes (range 4.93-426.63 minutes) using the app. The study results confirm the feasibility of implementing app-based delivery of cognitive behavioral therapy to family members of ICU patients.


Self-pumped phase conjugation in a liquid crystal light valve with a tilted feedback mirror.
We report self-pumped phase conjugation in a photorefractive liquid crystal light valve with a tilted feedback mirror. This is a new scheme for the self-generation of a phase-conjugate replica and can in general be applied to thin nonlinear layers, opening the way to distortion-correction applications of thin media.


Phylogenetic analyses of eurotiomycetous endophytes reveal their close affinities to Chaetothyriales, Eurotiales, and a new order - Phaeomoniellales.
Symbiotic fungi living in plants as endophytes, and in lichens as endolichenic fungi, cause no apparent symptoms to their hosts. They are ubiquitous, ecologically important, hyperdiverse, and represent a rich source of secondary compounds for new pharmaceutical and biocontrol products. Due in part to the lack of visible reproductive structures and other distinctive phenotypic traits for many species, the diversity and phylogenetic affiliations of these cryptic fungi are often poorly known. The goal of this study was to determine the phylogenetic placement of representative endophytes within the Eurotiomycetes (Pezizomycotina, Ascomycota), one of the most diverse and evolutionarily dynamic fungal classes, and to use that information to infer processes of macroevolution in trophic modes. Sequences of a single locus marker spanning the nuclear ribosomal internal transcribed spacer region (nrITS) and 600 base pairs at the 5' end of the nuclear ribosomal large subunit (nrLSU) were obtained from previous studies of >6000 endophytic and endolichenic fungi from diverse biogeographic locations and hosts. We conducted phylum-wide phylogenetic searches using this marker to determine which fungal strains belonged to Eurotiomycetes and the results were used as the basis for a class-wide, seven-locus phylogenetic study focusing on endophytic and endolichenic Eurotiomycetes. Our cumulative supermatrix-based analyses revealed that representative endophytes within Eurotiomycetes are distributed in three main clades: Eurotiales, Chaetothyriales and Phaeomoniellales ord. nov., a clade that had not yet been described formally. This new order, described herein, is sister to the clade including Verrucariales and Chaetothyriales. It appears to consist mainly of endophytes and plant pathogens. Morphological characters of endophytic Phaeomoniellales resemble those of the pathogenic genus Phaeomoniella. This study highlights the capacity of endophytic and endolichenic fungi to expand our understanding of the ecological modes associated with particular clades, and provides a first estimation of their phylogenetic relationships in the Eurotiomycetes.


Breaking down the cocktail party: Attentional modulation of cerebral audiovisual speech processing.
Recent studies utilizing electrophysiological speech envelope reconstruction have sparked renewed interest in the cocktail party effect by showing that auditory neurons entrain to selectively attended speech. Yet, the neural networks of attention to speech in naturalistic audiovisual settings with multiple sound sources remain poorly understood. We collected functional brain imaging data while participants viewed audiovisual video clips of lifelike dialogues with concurrent distracting speech in the background. Dialogues were presented in a full-factorial design, comprising task (listen to the dialogues vs. ignore them), audiovisual quality and semantic predictability. We used univariate analyses in combination with multivariate pattern analysis (MVPA) to study modulations of brain activity related to attentive processing of audiovisual speech. We found attentive speech processing to cause distinct spatiotemporal modulation profiles in distributed cortical areas including sensory and frontal-control networks. Semantic coherence modulated attention-related activation patterns in the earliest stages of auditory cortical processing, suggesting that the auditory cortex is involved in high-level speech processing. Our results corroborate views that emphasize the dynamic nature of attention, with task-specificity and context as cornerstones of the underlying neuro-cognitive mechanisms.


Systematic review: surveillance systems for early detection of bioterrorism-related diseases.
Given the threat of bioterrorism and the increasing availability of electronic data for surveillance, surveillance systems for the early detection of illnesses and syndromes potentially related to bioterrorism have proliferated. To critically evaluate the potential utility of existing surveillance systems for illnesses and syndromes related to bioterrorism. Databases of peer-reviewed articles (for example, MEDLINE for articles published from January 1985 to April 2002) and Web sites of relevant government and nongovernment agencies. Reports that described or evaluated systems for collecting, analyzing, or presenting surveillance data for bioterrorism-related illnesses or syndromes. From each included article, the authors abstracted information about the type of surveillance data collected; method of collection, analysis, and presentation of surveillance data; and outcomes of evaluations of the system. 17,510 article citations and 8088 government and nongovernmental Web sites were reviewed. From these, the authors included 115 systems that collect various surveillance reports, including 9 syndromic surveillance systems, 20 systems collecting bioterrorism detector data, 13 systems collecting influenza-related data, and 23 systems collecting laboratory and antimicrobial resistance data. Only the systems collecting syndromic surveillance data and detection system data were designed, at least in part, for bioterrorism preparedness applications. Syndromic surveillance systems have been deployed for both event-based and continuous bioterrorism surveillance. Few surveillance systems have been comprehensively evaluated. Only 3 systems have had both sensitivity and specificity evaluated. Data from some existing surveillance systems (particularly those developed by the military) may not be publicly available. Few surveillance systems have been specifically designed for collecting and analyzing data for the early detection of a bioterrorist event. Because current evaluations of surveillance systems for detecting bioterrorism and emerging infections are insufficient to characterize the timeliness or sensitivity and specificity, clinical and public health decision making based on these systems may be compromised.


Evaluation of intraaxial enhancing brain tumors on magnetic resonance imaging: intraindividual crossover comparison of gadobenate dimeglumine and gadopentetate dimeglumine for visualization and assessment, and implications for surgical intervention.
The goal in this article was to compare 0.1 mmol/kg doses of gadobenate dimeglumine (Gd-BOPTA) and gadopentetate dimeglumine, also known as gadolinium diethylenetriamine pentaacetic acid (Gd-DTPA), for enhanced magnetic resonance (MR) imaging of intraaxial brain tumors. Eighty-four patients with either intraaxial glioma (47 patients) or metastasis (37 patients) underwent two MR imaging examinations at 1.5 tesla, one with Gd-BOPTA as the contrast agent and the other with Gd-DTPA. The interval between fully randomized contrast medium administrations was 2 to 7 days. The T1-weighted spin echo and T2-weighted fast spin echo images were acquired before administration of contrast agents and T1-weighted spin echo images were obtained after the agents were administered. Acquisition parameters and postinjection acquisition times were identical for the two examinations in each patient. Three experienced readers working in a fully blinded fashion independently evaluated all images for degree and quality of available information (lesion contrast enhancement, lesion border delineation, definition of disease extent, visualization of the lesion's internal structures, global diagnostic preference) and quantitative enhancement (that is, the extent of lesion enhancement after contrast agent administration compared with that seen before its administration [hereafter referred to as percent enhancement], lesion/brain ratio, and contrast/noise ratio). Differences were tested with the Wilcoxon signed-rank test. Reader agreement was assessed using kappa statistics. Significantly better diagnostic information/imaging performance (p < 0.0001, all readers) was obtained with Gd-BOPTA for all visualization end points. Global preference for images obtained with Gd-BOPTA was expressed for 42 (50%), 52 (61.9%), and 56 (66.7%) of 84 patients (readers 1, 2, and 3, respectively) compared with images obtained with Gd-DTPA contrast in four (4.8%), six (7.1%), and three (3.6%) of 84 patients. Similar differences were noted for all other visualization end points. Significantly greater quantitative contrast enhancement (p < 0.04) was noted after administration of Gd-BOPTA. Reader agreement was good (kappa > 0.4). Lesion visualization, delineation, definition, and contrast enhancement are significantly better after administration of 0.1 mmol/kg Gd-BOPTA, potentially allowing better surgical planning and follow up and improved disease management.


Optical coherence tomography for the quantitative study of cerebrovascular physiology.
Doppler optical coherence tomography (DOCT) and OCT angiography are novel methods to investigate cerebrovascular physiology. In the rodent cortex, DOCT flow displays features characteristic of cerebral blood flow, including conservation along nonbranching vascular segments and at branch points. Moreover, DOCT flow values correlate with hydrogen clearance flow values when both are measured simultaneously. These data validate DOCT as a noninvasive quantitative method to measure tissue perfusion over a physiologic range.


Isolation and expression of a gene cluster responsible for biosynthesis of the glycopeptidolipid antigens of Mycobacterium avium.
Bacteria within the Mycobacterium avium complex are prominent in the environment and are a source of serious disseminated infections in patients with AIDS. Serovars of the M. avium complex are distinguished from all other mycobacteria and from one another by the presence of highly antigenic glycolipids, the glycopeptidolipids, on their surfaces. A genomic library of DNA from serovar 2 of the M. avium complex was constructed in the Escherichia coli-Mycobacterium shuttle cosmid, pYUB18, and used to clone and express in Mycobacterium smegmatis the genes responsible for the biosynthesis of the oligosaccharide segment of the M. avium serovar 2-specific glycopeptidolipid. The responsible gene cluster was mapped to a 22- to 27-kb functional region of the M. avium genome. The recombinant glycolipid was also isolated by high-pressure liquid chromatography and chemically characterized, by gas chromatography-mass spectrometry and fast atom bombardment-mass spectrometry, to demonstrate that the lipopeptide core originated in M. smegmatis, whereas the oligosaccharide segment arose from the cloned M. avium genes. This first-time demonstration of the cloning and expression, in a nonpathogenic mycobacterium, of the genes encoding complex cell wall glycoconjugates from a pathogenic mycobacterium presents a new approach for studying the role of such products in disease processes.


Bleeding time prolongation with streptokinase and its reduction with 1-desamino-8-D-arginine vasopressin.
The mechanism by which treatment with thrombolytic agents causes bleeding is not known. Recently, frequency of bleeding events has been shown to correlate with bleeding time, particularly in individuals treated with aspirin. We examined the effects of streptokinase (20,000-60,000 IU/kg) on bleeding time in 40 rabbits pretreated with aspirin, a model for fibrinolytic therapy. We then tested the effects of 1-desamino-8-D-arginine vasopressin (DDAVP) (0.3 microgram/kg), an agent known to reduce bleeding time in a variety of bleeding disorders, in 20 rabbits and compared the results with those of a control group of rabbits receiving normal saline placebo. Aspirin increased the bleeding time from a baseline mean +/- SEM value of 119 +/- 15 to 191 +/- 34 seconds in the control group and from 114 +/- 6 to 188 +/- 18 seconds in the experimental group. The addition of streptokinase increased the bleeding time to 592 +/- 119 seconds in the control group and 810 +/- 114 seconds in the experimental group (p = NS). Subsequent infusion of DDAVP decreased the bleeding time in the experimental group to 302 +/- 29 seconds (p less than 0.01 versus streptokinase) compared with 572 +/- 79 seconds (p = NS versus streptokinase) in the control animals given saline placebo. In a subset of rabbits receiving aspirin and streptokinase (40,000-60,000 IU/kg), samples were obtained for platelet aggregation (n = 16), von Willebrand factor antigen concentration (n = 17), and von Willebrand factor multimer distribution (n = 14). Maximal rates of ADP-induced platelet aggregation were not affected by DDAVP infusion, nor was the plasma concentration of von Willebrand factor antigen, quantified by an immunoradiometric assay, significantly affected by DDAVP infusion. Furthermore, the von Willebrand factor multimer ratio decreased with DDAVP administration. These findings indicate that aspirin and streptokinase combined result in a marked increase in bleeding time that can be reduced by DDAVP. This effect of DDAVP is not accompanied by an increase in platelet aggregation response, plasma von Willebrand factor antigen concentration, or von Willebrand factor multimer ratio.


Reforming health care: evidence from quantile regressions for counts.
I consider the problem of estimating the effect of a health care reform on the frequency of individual doctor visits when the reform effect is potentially different in different parts of the outcome distribution. Quantile regression is a powerful method for studying such heterogeneous treatment effects. Only recently has this method been extended to situations where the dependent variable is a (non-negative integer) count. An analysis of a 1997 health care reform in Germany shows that lower quantiles, such as the first quartile, fell by substantially larger amounts than what would have been predicted based on Poisson or negative binomial models.


The influence of both individual and area based socioeconomic status on temporal trends in Caesarean sections in Scotland 1980-2000.
Caesarean section rates have risen over the last 20 years. Elective Caesarean section rates have been shown to be linked to area deprivation in England, women in the most deprived areas were less likely to have an elective section than those in the most affluent areas. We examine whether individual social class, area deprivation or both are related to Caesarean sections in Scotland and investigate changes over time. Routine maternity discharge data from live singleton births in Scottish hospitals from three time periods were used; 1980-81 (n = 133,555), 1990-91 (n = 128,933) and 1999-2000 (n = 102,285). Multilevel logistic regression, with 3 levels (births, postcode sector and Health Board) was used to analyse emergency and elective Caesareans separately; analysis was further stratified by previous Caesarean section. The relative index of inequality (RII) was used to assess socioeconomic inequalities. Between 1980-81 and 1999-2000 the emergency section rate increased from 6.3% to 11.9% and the elective rate from 3.6% to 5.5%. In 1980-81 and 1990-91 emergency Caesareans were more likely among women at the bottom of the social class hierarchy compared to those at the top (RII = 1.14, 95%CI 1.00-1.25 and RII = 1.13, 1.03-1.23 respectively) and also among women in the most deprived areas compared to those in the most affluent (RII = 1.18, 1.05-1.32 and RII = 1.13, 1.02-1.26 respectively). In 1999-2000 the odds of an elective section were lower for women at the bottom of the social class hierarchy than those at the top (RII = 0.87, 0.76-1.00) and also lower in women in the most deprived areas compared to those in the most affluent (RII = 0.85, 0.73-0.99). Both individual social class and area deprivation are independently associated with Caesarean sections in Scotland. The tendency for disadvantaged women to be more likely to receive emergency sections disappeared at the same time as the likelihood of advantaged groups receiving elective sections increased.


"At-risk" kidney: How surgical factors influence renal functional preservation after partial nephrectomy.
To investigate the influence of surgical modifiable factors on chronic kidney disease upstaging in a contemporary cohort of patients with normal and "at-risk" kidneys undergoing partial nephrectomy. We reviewed 778 consecutive patients with (n = 634)/without (n = 144) chronic kidney disease or risk factors for chronic kidney disease in our institutional partial nephrectomy database. Chronic kidney disease upstaging was assessed using glomerular filtration rate measurements preoperatively and at 3-12 months postoperatively. Using a multivariate logistic regression, baseline clinicodemographic factors, and the operative measurements of excisional volume loss and warm and cold ischemia time on rates of chronic kidney disease upstaging were determined. Marginal effects were used to analyze the impact of ischemia time and generate interaction curves. Chronic kidney disease/risk factors for chronic kidney disease had equivalent rates of chronic kidney disease upstaging as the healthy kidney cohort (31.5% vs 38.2%, P = 0.15). Of the entire cohort, 2.8% were upstaged to stage IV-V chronic kidney disease. Multivariate analysis found a significant association between chronic kidney disease upstaging and excisional volume loss in both cohorts (no chronic kidney disease/risk factors for chronic kidney disease: odds ratio 1.63, P = 0.04; chronic kidney disease/risk factors for chronic kidney disease: odds ratio 1.42, P = 0.001). Only in the chronic kidney disease/risk factors for chronic kidney disease cohort, there was an association between ischemia type/duration and chronic kidney disease upstaging (odds ratio 1.04, P = 0.04). Warm ischemia began to predict an increased risk of chronic kidney disease upstaging at 17.6 min, which became statistically significant at 49 min. Chronic kidney disease upstaging is common after partial nephrectomy. Although volume loss unequivocally affects rates of upstaging irrespective of baseline renal function, warm ischemia time disproportionately influences "at-risk" kidneys. Therefore, strong consideration should be given to minimizing volume loss and using cold ischemia when extended clamp times are anticipated in "at-risk" kidneys.


Pulmonary artery catheter epidemiology of risk in pre-heart-transplant recipients.
Central-line-associated bloodstream infections (CLABSIs) are a known complication of central venous access. Pulmonary artery catheters (PAC) are frequently used in pre-heart-transplant patients, but the rate of CLABSI in this population is unknown. We sought to estimate the rate of CLABSI and identify factors associated with development of infection in patients actively listed for heart transplantation with a PAC. Retrospective cohort study. This study was conducted in 3 intensive care units at an academic tertiary-care center in Minnesota. 61 pre-heart-transplant patients in an intensive care unit with a PAC in place from January 2013 to December 2016, totaling 219 PACs. At-risk patients, pertinent risk factors, and demographic data were obtained using Mayo Clinic's Unified Data Platform. CLABSIs were identified through internal infection prevention and control data. Characteristics of PAC use and infection rate were collected and analyzed using Kaplan-Meier estimates and time-dependent Cox models. Among pre-heart-transplant patients with a PAC, there were 14 CLABSIs, for an infection rate of 5.46 of 1,000 PAC days (95% confidence interval [CI], 2.98-9.15). The most common causative organism was coagulase-negative Staphylococcus (79%). In unadjusted analyses, CLABSI was associated with shorter time to transplant (hazard ratio [HR], 2.49; P = .027), but not mortality (HR, 1.79; P = .355). The rate of CLABSI with PAC is high. Prolonged PAC use in the pre-heart-transplant population should be revisited.


Comprehensive analysis of glycolytic enzymes as therapeutic targets in the treatment of glioblastoma.
Major efforts have been put in anti-angiogenic treatment for glioblastoma (GBM), an aggressive and highly vascularized brain tumor with dismal prognosis. However clinical outcome with anti-angiogenic agents has been disappointing and tumors quickly develop escape mechanisms. In preclinical GBM models we have recently shown that bevacizumab, a blocking antibody against vascular endothelial growth factor, induces hypoxia in treated tumors, which is accompanied by increased glycolytic activity and tumor invasiveness. Genome-wide transcriptomic analysis of patient derived GBM cells including stem cell lines revealed a strong up-regulation of glycolysis-related genes in response to severe hypoxia. We therefore investigated the importance of glycolytic enzymes in GBM adaptation and survival under hypoxia, both in vitro and in vivo. We found that shRNA-mediated attenuation of glycolytic enzyme expression interfered with GBM growth under normoxic and hypoxic conditions in all cellular models. Using intracranial GBM xenografts we identified seven glycolytic genes whose knockdown led to a dramatic survival benefit in mice. The most drastic effect was observed for PFKP (PFK1, +21.8%) and PDK1 (+20.9%), followed by PGAM1 and ENO1 (+14.5% each), HK2 (+11.8%), ALDOA (+10.9%) and ENO2 (+7.2%). The increase in mouse survival after genetic interference was confirmed using chemical inhibition of PFK1 with clotrimazole. We thus provide a comprehensive analysis on the importance of the glycolytic pathway for GBM growth in vivo and propose PFK1 and PDK1 as the most promising therapeutic targets to address the metabolic escape mechanisms of GBM.


Six subgroups and extensive recent duplications characterize the evolution of the eukaryotic tubulin protein family.
Tubulins belong to the most abundant proteins in eukaryotes providing the backbone for many cellular substructures like the mitotic and meiotic spindles, the intracellular cytoskeletal network, and the axonemes of cilia and flagella. Homologs have even been reported for archaea and bacteria. However, a taxonomically broad and whole-genome-based analysis of the tubulin protein family has never been performed, and thus, the number of subfamilies, their taxonomic distribution, and the exact grouping of the supposed archaeal and bacterial homologs are unknown. Here, we present the analysis of 3,524 tubulins from 504 species. The tubulins formed six major subfamilies, α to ζ. Species of all major kingdoms of the eukaryotes encode members of these subfamilies implying that they must have already been present in the last common eukaryotic ancestor. The proposed archaeal homologs grouped together with the bacterial TubZ proteins as sister clade to the FtsZ proteins indicating that tubulins are unique to eukaryotes. Most species contained α- and/or β-tubulin gene duplicates resulting from recent branch- and species-specific duplication events. This shows that tubulins cannot be used for constructing species phylogenies without resolving their ortholog-paralog relationships. The many gene duplicates and also the independent loss of the δ-, ε-, or ζ-tubulins, which have been shown to be part of the triplet microtubules in basal bodies, suggest that tubulins can functionally substitute each other.


Evaluation of baseline-related suprathreshold testing for quick determination of visual field nonprogression.
To evaluate a commercially available means of baseline-related suprathreshold examination designed to detect visual field worsening. Patients for whom results of a baseline series of static-threshold visual field examinations were available underwent both a second static-threshold examination (full-threshold strategy; average time, 15 minutes) and a baseline-related suprathreshold examination ("fast-threshold" strategy; average time, 5 minutes). Most of the 1702 points examined were apparently unchanged from baseline, showing with either method only the degree of variation expected from the measurement inconsistency (short-term fluctuation). For points that did show a change, the changes shown by the two methods were correlated. Change in the field as a whole, represented by a cluster of locations showing deterioration, was evident more frequently with the standard testing strategy: 11 of 37 field examinations showed deterioration by both methods and an additional 11 examinations showed deterioration by the full-threshold method only. Each examination method identified pointwise changes not detected by the other, the combined effect of false-positive errors (imperfect specificity) and false-negative errors (imperfect sensitivity) with each of the two methods. The findings relating to clusters could represent a better sensitivity of the full-threshold method in detecting visual field deterioration, a better specificity of the suprathreshold method, or both.


Etiology of craniofacial malformations in mouse models of blepharophimosis, ptosis and epicanthus inversus syndrome.
Blepharophimosis, ptosis, epicanthus-inversus syndrome (BPES) is an autosomal dominant genetic disorder characterized by narrow palpebral fissures and eyelid levator muscle defects. BPES is often associated to premature ovarian insufficiency (BPES type I). FOXL2, a member of the forkhead transcription factor family, is the only gene known to be mutated in BPES. Foxl2 is essential for maintenance of ovarian identity, but the developmental origin of the facial malformations of BPES remains, so far, unexplained. In this study, we provide the first detailed account of the developmental processes leading to the craniofacial malformations associated to Foxl2. We show that, during development, Foxl2 is expressed both by Cranial Neural Crest Cells (CNCCs) and by Cranial Mesodermal Cells (CMCs), which give rise to skeletal (CNCCs and CMCs) and muscular (CMCs) components of the head. Using mice in which Foxl2 is selectively inactivated in either CNCCs or CMCs, we reveal that expression of Foxl2 in CNCCs is essential for the development of extraocular muscles. Indeed, inactivation of Foxl2 in CMCs has only minor effects on muscle development, whereas its inactivation in CNCCs provokes a severe hypoplasia of the levator palpabrae superioris and of the superior and inferior oblique muscles. We further show that Foxl2 deletion in either CNCCs or CMCs prevents eyelid closure and induces subtle skeletal developmental defects. Our results provide new insights in the complex developmental origin of human BPES and could help to understand the origin of other ocular anomalies associated to this syndrome.


The epidemiology and economic burden of Clostridium difficile infection in Korea.
The prevalence of Clostridium difficile infection and the associated burden have recently increased in many countries. While the main risk factors for C. difficile infection include old age and antibiotic use, the prevalence of this infection is increasing in low-risk groups. These trends highlight the need for research on C. difficile infection. This study pointed out the prevalence and economic burden of C. difficile infection and uses the representative national data which is primarily from the database of the Korean Health Insurance Review and Assessment Service, for 2008-2011. The annual economic cost was measured using a prevalence approach, which sums the costs incurred to treat C. difficile infection. C. difficile infection prevalence was estimated to have increased from 1.43 per 100,000 in 2008 to 5.06 per 100,000 in 2011. Moreover, mortality increased from 69 cases in 2008 to 172 in 2011. The economic cost increased concurrently, from $2.4 million in 2008 to $7.6 million, $10.5 million, and $15.8 million in 2009, 2010, and 2011, respectively. The increasing economic burden of C. difficile infection over the course of the study period emphasizes the need for intervention to minimize the burden of a preventable illness like C. difficile infection.


Utilization of Electrocardiographic P-wave Duration for AV Interval Optimization in Dual-Chamber Pacemakers.
Empiric programming of the atrio-ventricular (AV) delay is commonly performed during pacemaker implantation. Transmitral flow assessment by Doppler echocardiography can be used to find the optimal AV delay by Ritter's method, but this cannot easily be performed during pacemaker implantation. We sought to determine a non-invasive surrogate for this assessment. Since electrocardiographic P-wave duration estimates atrial activation time, we hypothesized this measurement may provide a more appropriate basis for programming AV intervals. A total of 19 patients were examined at the time of dual chamber pacemaker implantation, 13 (68%) being male with a mean age of 77. Each patient had the optimal AV interval determined by Ritter's method. The P-wave duration was measured independently on electrocardiograms using MUSE® Cardiology Information System (version 7.1.1). The relationship between P-wave duration and the optimal AV interval was analyzed. The P-wave duration and optimal AV delay were related by a correlation coefficient of 0.815 and a correction factor of 1.26. The mean BMI was 27. The presence of hypertension, atrial fibrillation, and valvular heart disease was 13 (68%), 3 (16%), and 2 (11%) respectively. Mean echocardiographic parameters included an ejection fraction of 58%, left atrial index of 32 ml/m(2), and diastolic dysfunction grade 1 (out of 4). In patients with dual chamber pacemakers in AV sequentially paced mode and normal EF, electrocardiographic P-wave duration correlates to the optimal AV delay by Ritter's method by a factor of 1.26.


Delaying antimalarial drug resistance with combination chemotherapy.
Resistance to antimalarial drugs arises when spontaneously occurring mutants with gene mutations or amplifications which confer reduced drug susceptibility are selected, and are then transmitted. Simultaneous use of two or more antimalarials with different modes of action and which therefore do not share the same resistance mechanisms will reduce the chance of selection, because the chance of a resistant mutant surviving is the product of the parasite mutation rates for the individual drugs, multiplied by the number of parasites in an infection that are exposed to the drugs. The artemisinin derivatives are very active antimalarials, which produce large reductions in parasite biomass per asexual cycle, and reduce malaria transmissibility. To date no resistance to these drugs has been reported. These drugs therefore make particularly effective combination partners. This suggests that antimalarial drugs should not be used alone in treatment, but always in combination, as in the treatment of tuberculosis or HIV, and that the combination should include artemisinin or one of its derivatives.


Usefulness of CDX2 and TTF-1 in differentiating gastrointestinal from pulmonary carcinoids.
Carcinoids of different organs appear morphologically indistinguishable. We studied the usefulness of differential expression of CDX2 and thyroid transcription factor-1 (TTF-1) in 78 gastrointestinal and pulmonary carcinoids and their metastases (n = 10). CDX2 staining of gastric biopsy specimens with neuroendocrine hyperplasia (n = 11) and various gastritides (n = 10) was also performed. All ileal (6/6 [100%]), 6 (86%) of 7 appendiceal, 3 (75%) of 4 duodenal, 1 (50%) of 2 ampullary, 12 (33%) of 18 rectal, 6 (30%) of 20 pancreatic, and 1 (17%) of 6 gastric carcinoids expressed CDX2 with variable intensity; none of the pulmonary carcinoids stained. Of 15 pulmonary carcinoids, 8 (53%) stained with TTF-1, but none of the gastrointestinal carcinoids did. CDX2 and TTF-1 staining profiles of primary and metastatic carcinoids were similar. CDX2+ gastric endocrine cells had a distribution similar to that of gastrin and enterochromaffin cells but not enterochromaffin-like cells. Our results suggest that CDX2 and TTF-1 have high specificity for gastrointestinal and pulmonary carcinoids, respectively.


Aerobic and anaerobic ethanol production by Mucor circinelloides during submerged growth.
The dimorphic organism Mucor circinelloides is currently being investigated as a potential host for heterologous protein production. The production of ethanol on pentose and hexose sugars was studied in submerged batch cultivations to further the general knowledge of Mucor physiology, with a view to the minimisation or elimination of the by-product ethanol for future process design. Large amounts of ethanol were produced during aerobic growth on glucose under non-oxygen limiting conditions, which is indicative of M. circinelloides being a Crabtree-positive organism. Ethanol production on galactose or xylose was less significant. The response of the organism to increased ethanol concentrations, both as the sole carbon source and in the presence of a sugar, was investigated in terms of biomass formation and morphology.


The N-terminal prodomain of sV23 is essential for the assembly of a functional vitelline membrane network in Drosophila.
The vitelline membrane is a specialized extracellular matrix that surrounds and protects the oocyte. Recent studies indicate that it also serves as a storage site for embryonic pattern determinants. sV23, a major vitelline membrane protein, is essential for the morphogenesis of the vitelline membrane as sV23 protein null mutants lay flaccid, infertile eggs. By analyzing a series of sV23 mutant transgenes in the sV23 protein null genetic background, we have shown that sV23 is secreted as a proprotein in functional excess and that C- and N-terminal prodomains are removed successively, following its deposition in the extracellular space. Although a target site for subtilisin-like convertases is essential for N-terminal processing, N-terminal processing is not necessary for the assembly of a functional vitelline membrane layer. While C-terminal truncations were tolerated, the removal of N-terminal sequences lead to the production of flaccid, infertile eggs with a soluble, rather than insoluble, vitelline membrane network. We propose that the hydrophobic N-terminal prodomain plays an early and essential role in aligning molecules within the vitelline membrane network, much like hydrophobic domains within elastin drive the assembly and alignment of molecules within elastin-based extracellular matrices.


Reactivation of Mutant-EGFR Degradation through Clathrin Inhibition Overcomes Resistance to EGFR Tyrosine Kinase Inhibitors.
Tyrosine kinase inhibitors (TKI) targeting mutant EGFR in non-small cell lung cancer (NSCLC) have been successful to control cancer growth, but acquired resistance inevitably occurs, including mutations directly on EGFR, for example, T790M and C797S. Strategies to prevent such acquired mutations by reducing mutant-EGFR expression have met limited success. Here, we propose a new model of mutant-EGFR trafficking and demonstrate that clathrin inhibition induces rapid degradation across a large panel of endogenous mutant-EGFR (Ex19del, L858R, and Ex20Ins). This panel included mutant-EGFR (T790M) resistant to the first- and second-generation EGFR inhibitors and to the third-generation TKI osimertinib and occurs through both mutational (C797S) and nonmutational EGFR mechanisms. Clathrin-mediated endocytosis inhibition of mutant EGFR induced a macropinocytosis-dependent lysosomal pathway associated with a loss of mutant-EGFR-dependent signaling (pAKT, pERK). Moreover, induction of this macropinocytic pathway led to robust apoptosis-dependent death across all mutant-EGFR cell lines tested, including those resistant to TKIs. We, therefore, propose a novel strategy to target mutant-EGFR refractory to approved existing TKI treatments in NSCLC and where new treatment strategies remain a key area of unmet need.Significance: These findings extend our mechanistic understanding of NSCLC mutant EGFR trafficking biology, the role that trafficking may play in resistance of mutant EGFR to tyrosine kinase inhibitors, and provide new therapeutic and biological insights to tackle this fundamental issue and improve benefit to patients. Cancer Res; 78(12); 3267-79. ©2018 AACR.


Comparison of Tissue-Disruption Methods for PCR-Based Detection of Plant Pathogens.
Polymerase chain reaction-based detection of plant-associated microbes depends on physical disruption of tissues of the host and microorganism in order to liberate nucleic acids during extraction. Using six types of plant tissues as well as an oospore preparation of Phytophthora capsici, we evaluated the use of pressure-cycling technology (PCT) compared with several common techniques for physical tissue disruption. With all tissues tested, bead-beating provided excellent yields of amplifiable nucleic acid, with a few inconsistent exceptions. The use of PCT did not consistently improve nucleic acid yields or "amplifiability". The use of a mortar and pestle to physically disrupt plant tissue also provided good results at low cost, though it was not consistently as effective as the bead-beater. Furthermore, handling of ground tissues in an open mortar may present more challenges in minimizing cross-contamination than working with tissues pulverized in a bead-beater tube.


Hearing, use of hearing protection, and attitudes towards noise among young American adults.
The purpose of the present study was to investigate possible associations between college students' attitudes, risk-taking behaviour related to noisy activities, and hearing problems such as threshold shifts or self-experienced hearing symptoms. The sample included 258 students aged between 17 and 21 enrolled at the University of Pennsylvania, USA. A questionnaire measuring attitudes towards noise, use of hearing protection, and self-reported hearing symptoms was distributed among the students. After completing the questionnaire a hearing screening, including pure-tone audiometry and tympanometry, was conducted. The result revealed that 26% had thresholds poorer than the screening level of 20 dBHL. Attitudes were significantly related to self-experienced hearing symptoms, but not to threshold shifts. Attitudes and noise sensitivity was, significantly related to use of hearing protection. Hearing protection use was found in activities such as using firearms, mowing lawns, and when using noisy tools but was less reported for concerts and discotheques. It can be concluded that the young adults in this study expose themselves to hearing risks, since the use of hearing protection is in general very low.


Genetic diversity for seed mineral composition in the wild legume Teramnus labialis.
Teramnus labialis (L.) Spreng. is a wild, tropical legume whose seeds are collected and used as a food source by tribal populations. In order to assess the potential of this legume to provide dietary minerals for humans, fourteen diverse accessions were grown under controlled, nutrient-replete conditions and seeds were harvested for mineral analysis. The germplasm originated from Indonesia, Africa, the Caribbean, and South America. Seed concentrations of phosphorus (P), potassium (K), sodium (Na), iron (Fe), copper (Cu), manganese (Mn), and zinc (Zn) were found to fall within the range of published values for several cultivated grain legumes, while calcium (Ca) and magnesium (Mg) were higher in T. labialis seeds. Mineral concentrations across the diverse accessions showed ranges of 1.3- to 2.3-fold for the macronutrient minerals (Ca, Mg, P, K) and 1.8- to 15.9-fold for the micronutrient minerals (Fe, Cu, Mn, Zn, and Na). The existing genetic diversity in this wild legume, especially for the essential minerals Ca and Mg, could be exploited to develop T. labialis as a new cultivated legume for tropical regions of the world.


Filtered multitensor tractography.
We describe a technique that uses tractography to drive the local fiber model estimation. Existing techniques use independent estimation at each voxel so there is no running knowledge of confidence in the estimated model fit. We formulate fiber tracking as recursive estimation: at each step of tracing the fiber, the current estimate is guided by those previous. To do this we perform tractography within a filter framework and use a discrete mixture of Gaussian tensors to model the signal. Starting from a seed point, each fiber is traced to its termination using an unscented Kalman filter to simultaneously fit the local model to the signal and propagate in the most consistent direction. Despite the presence of noise and uncertainty, this provides a causal estimate of the local structure at each point along the fiber. Using two- and three-fiber models we demonstrate in synthetic experiments that this approach significantly improves the angular resolution at crossings and branchings. In vivo experiments confirm the ability to trace through regions known to contain such crossing and branching while providing inherent path regularization.


Unsatisfactory knowledge and use of terminology regarding malnutrition, starvation, cachexia and sarcopenia among dietitians.
Clinical signs of malnutrition, starvation, cachexia and sarcopenia overlap, as they all imply muscle wasting to a various extent. However, the underlying mechanisms differ fundamentally and therefore distinction between these phenomena has therapeutic and prognostic implications. We aimed to determine whether dietitians in selected European countries have 'sufficient knowledge' regarding malnutrition, starvation, cachexia and sarcopenia, and use these terms in their daily clinical work. An anonymous online survey was performed among dietitians in Belgium, the Netherlands, Norway and Sweden. 'Sufficient knowledge' was defined as having mentioned at least two of the three common domains of malnutrition according to ESPEN definition of malnutrition (2011): 'nutritional balance', 'body composition' and 'functionality and clinical outcome', and a correct answer to three cases on starvation, cachexia and sarcopenia. Chi-square test was used to analyse differences in experience, work place and number of malnourished patients treated between dietitians with 'sufficient knowledge' vs. 'less sufficient knowledge'. 712/7186 responded to the questionnaire, of which data of 369 dietitians were included in the analysis (5%). The term 'malnutrition' is being used in clinical practice by 88% of the respondents. Starvation, cachexia and sarcopenia is being used by 3%, 30% and 12% respectively. The cases on starvation, cachexia and sarcopenia were correctly identified by 58%, 43% and 74% respectively. 13% of the respondents had 'sufficient knowledge'. 31% of the respondents identified all cases correctly. The proportion of respondents with 'sufficient knowledge' was significantly higher in those working in a hospital or in municipality (16%, P < 0.041), as compared to those working in other settings (7%). The results of our survey among dietitians in four European countries show that the percentage of dietitians with 'sufficient knowledge' regarding malnutrition, starvation, cachexia and sarcopenia is unsatisfactory (13%). The terms starvation, cachexia and sarcopenia are not often used by dietitians in daily clinical work. As only one-third (31%) of dietitians identified all cases correctly, the results of this study seem to indicate that nutrition-related disorders are suboptimally recognized in clinical practice, which might have a negative impact on nutritional treatment. The results of our study require confirmation in a larger sample of dietitians.


TUBERCULAR ALLERGY WITHOUT INFECTION.
1. Guinea pigs can be rendered hypersensitive to tuberculo-protein by small, repeated, intradermal injections of active tuberculo-protein. 2. The addition of tuberculo-phosphatide to the protein speeds up the process of sensitization and enhances it so that the reactions become indurated and necrotic, closely simulating those of the disease. 3. Active tuberculo-proteins induce a new formation of monocytes and some epithelioid cells. The addition of phosphatide to the protein brings about a massive formation of epithelioid cells. 4. With the increased cellular reaction to the mixed injections may be correlated the increase in the speed and intensity of the sensitization. 5. The intradermal route is the best for these sensitizations, probably because it provides the greatest dose per cell of the sensitizing agent. 6. The degree of sensitization artificially obtainable by the synergistic action of tuberculo-phosphatide and tuberculo-protein is quite comparable to the degree of sensitization naturally occurring in tuberculous animals; moreover, this degree of sensitization may be induced with amounts of the materials from the bacilli which could conceivably be present in the tissues of an infected host.


Cell surface accessibility of GLUT4 glucose transporters in insulin-stimulated rat adipose cells. Modulation by isoprenaline and adenosine.
Insulin-stimulated glucose transport activity in rat adipocytes is inhibited by isoprenaline and enhanced by adenosine. Both of these effects occur without corresponding changes in the subcellular distribution of the GLUT4 glucose transporter isoform. In this paper, we have utilized the impermeant, exofacial bis-mannose glucose transporter-specific photolabel, 2-N-4-(1-azi-2,2,2-trifluoroethyl)benzoyl-1,3-bis-(D-mannos- 4-yloxy)-2-propylamine (ATB-BMPA) [Clark & Holman (1990) Biochem. J. 269, 615-622], to examine the cell surface accessibility of GLUT4 glucose transporters under these conditions. Compared with cells treated with insulin alone, adenosine in the presence of insulin increased the accessibility of GLUT4 to the extracellular photolabel by approximately 25%, consistent with its enhancement of insulin-stimulated glucose transport activity; the plasma membrane concentration of GLUT4 as assessed by Western blotting was unchanged. Conversely, isoprenaline, in the absence of adenosine, promoted a time-dependent (t1/2 approximately 2 min) decrease in the accessibility of insulin-stimulated cell surface GLUT4 of > 50%, which directly correlated with the observed inhibition of transport activity; the plasma membrane concentration of GLUT4 decreased by 0-15%. Photolabelling the corresponding plasma membranes revealed that these alterations in the ability of the photolabel to bind to GLUT4 are transient, as the levels of both photolabel incorporation and plasma membrane glucose transport activity were consistent with the observed GLUT4 concentration. These data suggest that insulin-stimulated GLUT4 glucose transporters can exist in two distinct states within the adipocyte plasma membrane, one which is functional and accessible to extracellular substrate, and one which is non-functional and unable to bind extracellular substrate. These effects are only observed in the intact adipocyte and are not retained in plasma membranes isolated from these cells when analysed for their ability to transport glucose or bind photolabel.


Preventive intervention in diabetes: a new model for continuing medical education.
Competence and skills in overcoming clinical inertia for diabetes treatment, and actually supporting and assisting the patient through adherence and compliance (as opposed to just reiterating what they "should" be doing and then assigning them the blame if they fail) is a key component to success in addressing diabetes, and to date it is a component that has received little formal attention. To improve and systematize diabetes care, it is critical to move beyond the "traditional" continuing medical education (CME) model of imparting knowledge as the entirety of the educational effort, and move toward a focus on Performance Improvement CME. This new approach does not just teach new information but also provides support for improvements where needed most within practice systems based on targeted data-based on self-assessments for the entire system of care. Joslin data conclude that this new approach will benefit support, clinical, and office teams as well as the specialist. In short, the Performance Improvement CME structure reflects the needed components of the successful practice today, particularly for chronic conditions such as diabetes, including the focus on interdisciplinary team care and on quality improvement, which is becoming more and more aligned with reimbursement schemes, public and private, in the U.S.


Radiation-Engineered Functional Nanoparticles in Aqueous Systems.
Controlled synthesis of nanoscalar and nanostructured materials enables the development of novel functional materials with fine-tuned optical, mechanical, electronic, magnetic, conductive and catalytic properties that are of use in numerous applications. These materials have also found their potential use in medicine as vehicles for drug delivery, in diagnostics or in combinations thereof. In principle, nanoparticles can be divided into two broad categories, organic and inorganic nanoparticles. For both types of nanoparticles there are numerous possible synthetic routes. Considering the large difference in nature of these materials and the elementary reactions involved in the synthetic routes, most manufacturing techniques are complex and only suitable for one type of particle. Interestingly, radiation chemistry, i.e., the use of ionizing radiation from radioisotopes and accelerators to induce nanomaterials or chemical changes in materials, has proven to be a versatile tool for controlled manufacturing of both organic and inorganic nanoparticles. The advantages of using radiation chemistry for this purpose are many, such as low energy consumption, minimal use of potentially harmful chemicals and simple production schemes. For medical applications one more advantage is that the material can be sterile as manufactured. Radiation-induced synthesis can be carried out in aqueous systems, which minimizes the use of organic solvents and the need for separation and purification of the final product. The radiation chemistry of water is well known, as are the various ways of fine-tuning the reactivity of the system towards a desired target by adding different solutes. This, in combination with the controllable and adjustable irradiation process parameters, makes the technique superior to most other chemical methods. In this review, we discuss the fundamentals of radiation chemistry and radiation-induced synthesis of nanoparticles in aqueous solutions. The impact of dose and dose rate as well as of controlled addition of various solutes on the final particle composition, size and size distribution are described in detail and discussed in terms of reaction mechanism and kinetics.


A chemically defined carrier for the delivery of human mesenchymal stem/stromal cells to skin wounds.
Skin has a remarkable capacity for regeneration, but age- and diabetes-related vascular problems lead to chronic non-healing wounds for many thousands of U.K. patients. There is a need for new therapeutic approaches to treat these resistant wounds. Donor mesenchymal stem/stromal cells (MSCs) have been shown to assist cutaneous wound healing by accelerating re-epithelialization. The aim of this work was to devise a low risk and convenient delivery method for transferring these cells to wound beds. Plasma polymerization was used to functionalize the surface of medical-grade silicone with acrylic acid. Cells attached well to these carriers, and culture for up to 3 days on the carriers did not significantly affect their phenotype or ability to support vascular tubule formation. These carriers were then used to transfer MSCs onto human dermis. Cell transfer was confirmed using an MTT assay to assess viable cell numbers and enhanced green fluorescent protein-labeled MSCs to demonstrate that the cells post-transfer attached to the dermis. We conclude that this synthetic carrier membrane is a promising approach for delivery of therapeutic MSCs and opens the way for future studies to evaluate its impact on repairing difficult skin wounds.


Isolation and characterization of neural crest-derived stem cells from dental pulp of neonatal mice.
Dental pulp stem cells (DPSCs) are shown to reside within the tooth and play an important role in dentin regeneration. DPSCs were first isolated and characterized from human teeth and most studies have focused on using this adult stem cell for clinical applications. However, mouse DPSCs have not been well characterized and their origin(s) have not yet been elucidated. Herein we examined if murine DPSCs are neural crest derived and determined their in vitro and in vivo capacity. DPSCs from neonatal murine tooth pulp expressed embryonic stem cell and neural crest related genes, but lacked expression of mesodermal genes. Cells isolated from the Wnt1-Cre/R26R-LacZ model, a reporter of neural crest-derived tissues, indicated that DPSCs were Wnt1-marked and therefore of neural crest origin. Clonal DPSCs showed multi-differentiation in neural crest lineage for odontoblasts, chondrocytes, adipocytes, neurons, and smooth muscles. Following in vivo subcutaneous transplantation with hydroxyapatite/tricalcium phosphate, based on tissue/cell morphology and specific antibody staining, the clones differentiated into odontoblast-like cells and produced dentin-like structure. Conversely, bone marrow stromal cells (BMSCs) gave rise to osteoblast-like cells and generated bone-like structure. Interestingly, the capillary distribution in the DPSC transplants showed close proximity to odontoblasts whereas in the BMSC transplants bone condensations were distant to capillaries resembling dentinogenesis in the former vs. osteogenesis in the latter. Thus we demonstrate the existence of neural crest-derived DPSCs with differentiation capacity into cranial mesenchymal tissues and other neural crest-derived tissues. In turn, DPSCs hold promise as a source for regenerating cranial mesenchyme and other neural crest derived tissues.


[Comparison of nursing activities reflected in nursing notes and in-depth interviews of nurses in an acute hospital].
The purpose of this study was to compare the nursing activities delineated by interview of nurses with those on nursing notes. The participants of interview were 18 nurses working in medical and surgical units of a large hospital in Seoul. Each nurse was asked to choose one patient who demand most nursing care among her patients. The nurse was then interviewed to describe what her nursing activities for the patient was that day. The audio-taped interview was transcribed and the content was analyzed by researchers. Nursing notes of each nurses' patients were copied and the content analyzed by researchers. Finally, themes from the interview data and those from nursing notes were compared. Activities related to emotional or psychological nursing, education for patient and families, and problem solving related to treatment or nursing procedure were most often omitted in nursing notes. Most of the documentation in nursing notes were related to physical condition of patients or physician's orders. Nurses described that they will do better recording if they were given less patient care responsibility, had better nursing knowledge, had better recording system, and received more training on nursing record. Nursing notes did not reflect nursing activities properly. Few independent nursing roles were documented in the nursing notes. Development of nursing education program and nursing record system is needed for improvement of nursing record.


Acoustic NLOS Identification Using Acoustic Channel Characteristics for Smartphone Indoor Localization.
As the demand for indoor localization is increasing to support our daily life in large and complex indoor environments, sound-based localization technologies have attracted researchers' attention because they have the advantages of being fully compatible with commercial off-the-shelf (COTS) smartphones, they have high positioning accuracy and low-cost infrastructure. However, the non-line-of-sight (NLOS) phenomenon poses a great challenge and has become the technology bottleneck for practical applications of acoustic smartphone indoor localization. Through identifying and discarding the NLOS measurements, the positioning performance can be improved by incorporating only the LOS measurements. In this paper, we focus on identifying NLOS components by characterizing the acoustic channels. Firstly, by analyzing indoor acoustic propagations, the changes of acoustic channel from the line-of-sight (LOS) condition to the NLOS condition are characterized as the difference of channel gain and channel delay between the two propagation scenarios. Then, an efficient approach to estimate relative channel gain and delay based on the cross-correlation method is proposed, which considers the mitigation of the Doppler Effect and reduction of the computational complexity. Nine novel features have been extracted, and a support vector machine (SVM) classifier with a radial-based function (RBF) kernel is used to realize NLOS identification. The experimental result with an overall 98.9% classification accuracy based on a data set with more than 10 thousand measurements shows that the proposed identification approach and features are effective in acoustic NLOS identification for acoustic indoor localization via a smartphone. In order to further evaluate the performance of the proposed SVM classifier, the performance of an SVM classifier is compared with that of traditional classifiers based on logistic regression (LR) and linear discriminant analysis (LDA). The results also show that a SVM with the RBF kernel function method outperforms others in acoustic NLOS identification.


Constrained watershed method to infer morphology of mammalian cells in microscopic images.
Precise information about the size, shape, temporal dynamics, and spatial distribution of cells is beneficial for the understanding of cell behavior and may play a key role in drug development, regenerative medicine, and disease research. The traditional method of manual observation and measurement of cells from microscopic images is tedious, expensive, and time consuming. Thus, automated methods are in high demand, especially given the increasing quantity of cell data being collected. In this article, an automated method to measure cell morphology from microscopic images is proposed to outline the boundaries of individual hematopoietic stem cells (HSCs). The proposed method outlines the cell regions using a constrained watershed method which is derived as an inverse problem. The experimental results generated by applying the proposed method to different HSC image sequences showed robust performance to detect and segment individual and dividing cells. The performance of the proposed method for individual cell segmentation for single frame high-resolution images was more than 97%, and decreased slightly to 90% for low-resolution multiframe stitched images.


Long term trends in control of hypertension in the Northern Sweden MONICA study 1986-2009.
A large proportion of treated hypertensive subjects do not achieve target blood pressure (BP) levels. We investigated trends in treatment and BP levels in the population, and among treated hypertensive subjects in northern Sweden. The six Northern Sweden MONICA population surveys 1986 to 2009, included 6342 subjects aged 45 to 74 years of age, participation rate 79.3%. Factors associated with lack of BP control are presented for 1106 participants in 2009. BP control was defined as a systolic BP <140 and a diastolic BP <90 mm Hg among treated hypertensive patients. Between 1986 and 2009, the proportion of the population that received antihypertensive treatment increased. The proportion of the whole population having BP <140/90 mm Hg increased for all (p < 0.001 for each subgroup), except for men 45-55 years old. In 2009, 62.4% of the population had BP <140/90 mm Hg, 67.2% in women and 58.1% in men (p = 0.002). In the group of treated hypertensive patients, the proportion having BP control increased (p < 0.001) with no difference between sex or age groups. In 2009 52.1% of treated hypertensives had BP control. In 2009, adequate BP control among treated hypertensive patients was 63.9% for those with BMI <25, but only 48.8% for those with BMI > 25 (p = 0.015). Abdominal obesity was associated with less BP control (48.1%) than without abdominal obesity (66.2%, p = 0.007). Women who were physically inactive had better BP control than those who were active (p = 0.03). Men treated with two or more antihypertensive drugs were 50% more likely to reach target BP than men with monotherapy (60.4% vs. 40.0 %, p = 0.035). Rural or urban living, level of education, diabetes mellitus or having a high cardiovascular risk were not associated with better BP control. Antihypertensive treatment and BP control have increased in northern Sweden since 1986, although in 2009 still barely half of the treated patients achieved adequate BP levels. Intensified treatment and weight reduction may help to further improve BP control.


The relationship between physical activity and executive function performance in children with attention-deficit hyperactivity disorder.
Children with attention-deficit hyperactivity disorder (AD/HD) consistently perform worse on executive function (EF) tasks relative to those without AD/HD. Physical activity has a small effect on cognition in children and may be particularly beneficial for children with AD/HD by impacting fundamental EF deficiencies that characterize this disorder. The purpose of this study was to explore the extent to which physical activity is associated with EF in children with AD/HD. Eighteen boys (M age = 10.61, SD = 1.50) with AD/HD were recruited to complete four EF tasks. Physical activity was measured with an accelerometer that provided daily minutes of moderate-to-vigorous intensity physical activity; this measure was a significant predictor of performance on the Tower of London planning task, adjusted R² = .28, F(1, 16) = 7.61, p < .05, and was positively associated with other EF measures. These results suggest that higher physical activity is associated with better EF performance in AD/HD children.


Energy coupling to the transport of inorganic phosphate in Escherichia coli K12.
The nature of the energy source for phosphate transport was studied in strains of Escherichia coli in which either one of the two major systems (PIT, PST) for phosphate transport was present. In the PIT system, phosphate transport is coupled to the proton-motive force. The energy source for the PST system appears to be phosphate-bond energy, as has been found in other systems involving binding proteins. High concentration gradients of phosphate (between 100 and 500) are established by both systems.


Accuracy of linear measurement and the measurement limits of thin objects with cone beam computed tomography: effects of measurement directions and of phantom locations in the fields of view.
The directional dependence of accuracy with cone beam computed tomography (CBCT) has not been investigated thoroughly. The purpose of the present study was to clarify the effects of measurement direction and of phantom locations in the fields of view (FOVs) on the accuracy of linear measurement and on the limits of measuring thin objects with CBCT. An aluminum phantom was scanned by CBCT. The thickness in both the longitudinal and horizontal directions (LD and HD) was measured at both the center and periphery in the three FOVs. The length was determined by a 50% relative threshold method to eliminate observer-dependent measurement errors. The measurement limits of a thin object were assessed in thin parts of the phantom (thickness, 0.3 to 1.0 mm). The measurement accuracy in the LD was excellent (within 1 pixel), while that in the HD was fair (0 to 2.35 pixels difference); a slight overestimation was found near the center of the phantom (1.06 to 2.35 pixels difference) in comparison to that of the edges (within 1 pixel difference). The overestimation was more marked at the longitudinal periphery than at the center of each FOV. A thickness of at least three to four pixels was necessary to keep errors within the one-pixel range along both directions. The accuracy of linear measurement with CBCT is excellent, especially when measuring in the LD. Distances are slightly overestimated in the HD near the center of the phantom. Close attention is therefore necessary when planning the placement of implants adjacent to horizontal vital structures. Second, a thickness of at least 3 to 4 pixels was necessary to maintain high accuracy for linear measurement. This must be taken into consideration when measuring a minute structure, such as thin cortical bone.