Hematologic abnormalities in Fanconi anemia: an International Fanconi Anemia Registry study.
We analyzed data from 388 subjects with Fanconi anemia reported to the International Fanconi Anemia Registry (IFAR). Of those, 332 developed hematologic abnormalities at a median age of 7 years (range, birth to 31 years). Actuarial risk of developing hematopoietic abnormalities was 98% (95% confidence interval, 93% to 99%) by 40 years of age. Common hematologic abnormalities were thrombocytopenia and pancytopenia. These were often associated with decreased bone marrow (BM) cellularity (75% of cases studied). Clonal cytogenetic abnormalities developed in 23 of 68 persons with BM failure who had adequate studies. Actuarial risk of clonal cytogenetic abnormalities during BM failure was 67% (47% to 87%) by 30 years of age. Fifty-nine subjects developed myelodysplastic syndrome (MDS) or acute myelogenous leukemia (AML). Actuarial risk of MDS or AML was 52% (37% to 67%) by 40 years of age. Risk was higher in persons with than in those without a prior clonal cytogenetic abnormality (3% [0% to 9%] v 35% [0% to 79%]; P = .006). One hundred twenty persons died of hematologic causes including BM failure, MDS or AML and treatment related complications. Actuarial risk of death from hematologic causes was 81% (67% to 90%) by 40 years of age.


Delivery of cancer screening: how important is the preventive health examination?
Patients and physicians strongly endorse the importance of preventive or periodic health examinations (PHEs). However, the extent to which PHEs contribute to the delivery of cancer screening is uncertain. In a retrospective cohort study, we determined the association between receipt of a PHE and cancer testing in a population-based sample of enrollees in a Washington State health plan who were aged 52 to 78 years and eligible for colorectal, breast, or prostate cancer screening in 2002-2003 (N = 64 288). Outcomes included completion of any colorectal cancer testing (fecal occult blood testing, sigmoidoscopy, colonoscopy, or barium enema), screening mammography, and prostate-specific antigen testing. More than half (52.4%) of the enrollees received a PHE during the study period. After adjusting for demographics, comorbidity, number of outpatient visits, and historical preventive service use before January 1, 2002, receipt of a PHE was significantly associated with completion of colorectal cancer testing (incidence difference, 40.4% [95% confidence interval (CI), 39.4%-41.3%]; relative incidence, 3.47 [95% CI, 3.34-3.59]), screening mammography [incidence difference, 14.2% [95% CI, 12.7%-15.7%]; relative incidence, 1.23 [95% CI, 1.20-1.25]), and prostate-specific antigen testing (incidence difference, 39.4% [95% CI, 38.3%-40.5%]; relative incidence, 3.06 [95% CI, 2.95-3.18]). Among managed care enrollees eligible for cancer screening, PHE receipt is associated with completion of colorectal, breast, and prostate cancer testing. In similar populations, the PHE may serve as a clinically important forum for the promotion of evidence-based colorectal cancer and breast cancer screening and of screening with relatively less empirical support, such as prostate cancer screening.


Epidemiological characteristics and resource use in neonates with bronchopulmonary dysplasia: 1993-2006.
To determine the trends in incidence of diagnosis of bronchopulmonary dysplasia (BPD) and associated health services use for the neonatal hospitalization of patients with BPD in an era of changing definitions and management. All neonatal hospitalization records available through the Nationwide Inpatient Sample, 1993-2006, were analyzed. Multivariable regression analyses were performed for incidence of BPD diagnosis and associated hospital length of stay and charges. Multiple models were constructed to assess the roles of changes in diagnosis of very low birth weight (VLBW) neonates and different modalities of respiratory support used for treatment. The absolute incidence of diagnosis of BPD fell 3.3% annually (P = .0009) between 1993 and 2006 coincident with a 3.5-fold increase in the use of noninvasive respiratory support in patients with BPD. When data were controlled for demographic factors, this significant decrease in incidence persisted at a rate of 4.3% annually (P = .0002). All models demonstrated a rise in hospital length of stay and financial charges for the neonatal hospitalization of patients with BPD. The incidence of BPD adjusted for frequency of prolonged mechanical ventilation also decreased but only by 2.8% annually (P = .0075). The incidence of diagnosis of BPD decreased significantly between 1993 and 2006. In well-controlled models, birth hospitalization charges for these patients rose during the same period. Less invasive ventilatory support may improve respiratory outcomes of VLBW neonates.


Early care and education for children in immigrant families.
A substantial and growing share of the population, immigrant children are more likely than children with native-born parents to face a variety of circumstances, such as low family income, low parental education, and language barriers that place them at risk of developmental delay and poor academic performance once they enter school. Lynn Karoly and Gabriella Gonzalez examine the current role of and future potential for early care and education (ECE) programs in promoting healthy development for immigrant children. Participation in center-based care and preschool programs has been shown to have substantial short-term benefits and may also lead to long-term gains as children go through school and enter adulthood. Yet, overall, immigrant children have lower rates of participation in nonparental care of any type, including center-based ECE programs, than their native counterparts. Much of the participation gap can be explained by just a few economic and sociodemographic factors, the authors find. To some extent, the factors that affect disadvantaged immigrant children resemble those of their similarly disadvantaged native counterparts. Affordability, availability, and access to ECE programs are structural barriers for many immigrant families, as they are for disadvantaged families more generally. Language barriers, bureaucratic complexity, and distrust of government programs, especially among undocumented immigrants, are unique challenges that may prevent some immigrant families from taking advantage of ECE programs, even when their children might qualify for subsidies. Cultural preferences for parental care at home can also be a barrier. Thus the authors suggest that policy makers follow a two-pronged approach for improving ECE participation rates among immigrant children. First, they note, federal and state ECE programs that target disadvantaged children in general are likely to benefit disadvantaged immigrant children as well. Making preschool attendance universal is one way to benefit all immigrant children. Second, participation gaps that stem from the unique obstacles facing immigrants, such as language barriers and informational gaps, can be addressed through the way publicly subsidized and private or nonprofit programs are structured.


Adolescents of the U.S. National Longitudinal Lesbian Family Study: sexual orientation, sexual behavior, and sexual risk exposure.
This study assessed Kinsey self-ratings and lifetime sexual experiences of 17-year-olds whose lesbian mothers enrolled before these offspring were born in the longest-running, prospective study of same-sex parented families, with a 93% retention rate to date. Data for the current report were gathered through online questionnaires completed by 78 adolescent offspring (39 girls and 39 boys). The adolescents were asked if they had ever been abused and, if so, to specify by whom and the type of abuse (verbal, emotional, physical, or sexual). They were also asked to specify their sexual identity on the Kinsey scale, between exclusively heterosexual and exclusively homosexual. Lifetime sexual behavior was assessed through questions about heterosexual and same-sex contact, age of first sexual experience, contraception use, and pregnancy. The results revealed that there were no reports of physical or sexual victimization by a parent or other caregiver. Regarding sexual orientation, 18.9% of the adolescent girls and 2.7% of the adolescent boys self-rated in the bisexual spectrum, and 0% of girls and 5.4% of boys self-rated as predominantly-to-exclusively homosexual. When compared with age- and gender-matched adolescents of the National Survey of Family Growth, the study offspring were significantly older at the time of their first heterosexual contact, and the daughters of lesbian mothers were significantly more likely to have had same-sex contact. These findings suggest that adolescents reared in lesbian families are less likely than their peers to be victimized by a parent or other caregiver, and that daughters of lesbian mothers are more likely to engage in same-sex behavior and to identify as bisexual.


EpiBeds: Data informed modelling of the COVID-19 hospital burden in England.
The first year of the COVID-19 pandemic put considerable strain on healthcare systems worldwide. In order to predict the effect of the local epidemic on hospital capacity in England, we used a variety of data streams to inform the construction and parameterisation of a hospital progression model, EpiBeds, which was coupled to a model of the generalised epidemic. In this model, individuals progress through different pathways (e.g. may recover, die, or progress to intensive care and recover or die) and data from a partially complete patient-pathway line-list was used to provide initial estimates of the mean duration that individuals spend in the different hospital compartments. We then fitted EpiBeds using complete data on hospital occupancy and hospital deaths, enabling estimation of the proportion of individuals that follow the different clinical pathways, the reproduction number of the generalised epidemic, and to make short-term predictions of hospital bed demand. The construction of EpiBeds makes it straightforward to adapt to different patient pathways and settings beyond England. As part of the UK response to the pandemic, EpiBeds provided weekly forecasts to the NHS for hospital bed occupancy and admissions in England, Wales, Scotland, and Northern Ireland at national and regional scales.


Inter-layer charge disproportionation in the dual-layer organic metal (tTTF-I)2ClO4 with unsymmetrical I···O halogen bond interactions.
A mixed-valence salt of tTTF-I with ClO4(-), formulated as (tTTF-I)2ClO4, is characterized by the presence of two crystallographically independent donor molecules, segregated in different layers and linked together through I···O interactions with the ClO4(-) anion disordered at room temperature. The tTTF-I donor molecule was prepared by metallation of tTTF (trimethylene tetrathiafulvalene) followed by reaction with iodine to afford the mono and diiodo derivatives tTTF-I and tTTFI2, respectively. The crystal structure of the latter neutral tTTFI2 shows the occurrence of strong type II, II halogen bond interactions. Band structure calculations of the dual-layer structure of the 2 : 1 salt (tTTF-I)2ClO4 show co-existence of both 1D open and 2D closed Fermi surfaces. The salt undergoes a metal-insulator phase transition at T(MI) = 90 K, associated with an electronic dimensionality decrease, since already at 100 K, the 2D part of the Fermi surface transforms into 1D corrugated planes. High resolution X-ray investigations performed at 100 K, combined with multipolar refinements, indicate an approximately equivalent +0.5e charge in both donor molecules, as also deduced from the intramolecular bond distances. On the other hand, Raman spectroscopic investigations show that at ambient temperature the charge is actually distributed non-uniformly in conducting layers of tTTF-I molecules, with the identification of molecules with charges +1, +0.5, 0e, while at low temperature the charge distribution becomes essentially uniform (+0.5e), as confirmed from the X-ray high resolution data. These apparently contradictory behaviors are actually a consequence of a partial electron transfer between the two independent slabs to reach a common Fermi level in the metallic phase.


Developing a scorecard to assess global progress in scaling up diarrhea control tools: a qualitative study of academic leaders and implementers.
In 2010, diarrhea caused 0.75 million child deaths, accounting for nearly 12% of all under-five mortality worldwide. Many evidence-based interventions can reduce diarrhea mortality, including oral rehydration solution (ORS), zinc, and improved sanitation. Yet global coverage levels of such interventions remain low. A new scorecard of diarrhea control, showing how different countries are performing in their control efforts, could draw greater attention to the low coverage levels of proven interventions. We conducted in-depth qualitative interviews with 21 experts, purposively sampled for their relevant academic or implementation expertise, to explore their views on (a) the value of a scorecard of global diarrhea control and (b) which indicators should be included in such a scorecard. We then conducted a ranking exercise in which we compiled a list of all 49 indicators suggested by the experts, sent the list to the 21 experts, and asked them to choose 10 indicators that they would include and 10 that they would exclude from such a scorecard. Finally, we created a "prototype" scorecard based on the 9 highest-ranked indicators. Key themes that emerged from coding the interview transcripts were: a scorecard could facilitate country comparisons; it could help to identify best practices, set priorities, and spur donor action; and it could help with goal-setting and accountability in diarrhea control. The nine highest ranking indicators, in descending order, were ORS coverage, rotavirus vaccine coverage, zinc coverage, diarrhea-specific mortality rate, diarrhea prevalence, proportion of population with access to improved sanitation, proportion with access to improved drinking water, exclusive breastfeeding coverage, and measles vaccine coverage. A new scorecard of global diarrhea control could help track progress, focus prevention and treatment efforts on the most effective interventions, establish transparency and accountability, and alert donors and ministries of health to inadequacies in diarrhea control efforts.


Use of calixarenes bearing diazonium groups for the development of robust monolayers with unique tailored properties.
Surface modification represents an active field of research that finds applications, amongst others, in the development of medical devices, sensors and biosensors, anti-biofouling materials, self-cleaning surfaces, surfaces with controlled wettability, corrosion resistance, heterogeneous catalysis and microelectronics. For some applications, surface functionalization with a nanometric-size monolayer is desired. In this review, efforts to covalently functionalize a wide array of surfaces with calixarenes bearing diazonium groups are described. More specifically, methodologies to obtain monolayers of calix[4 or 6]arene derivatives on conductive, semi-conductive or insulating surfaces as well as on nanoparticles are presented. The main advantages of this general surface modification strategy (i.e. formation of true monolayers that can be post-functionalized, high robustness and control over the composition of the calixarene-based coating) and its current scope of applications and future challenges are discussed.


Violent behaviour among Turkish high school students and correlates of physical fighting.
The purpose of this study was to provide data about the prevalence of violent behaviour among high school students living in Istanbul and to determine the correlates of physical fighting. This study involved the completion of a modified version of 'Health Behaviour in School Age Children (HBSC) 1997/1998' survey questionnaire by 4153 grade 9-11 students. Chi square tests and forward stepwise multiple logistic regression models were used for statistical analyses. During the last 12 months preceding the survey 42% of students (n=1720) reported that they had been in a physical fight; 7% (n=274) reported that they were involved in a fight which required medical treatment. During the last school term 19% (n=768) bullied others at school; 30% (n=1255) reported having been bullied at school; 7% (n=309) reported that they had been bullied with a weapon on school grounds; 8% (n=346) reported that they carried a weapon on school grounds. In logistic regression analyses being male, poor mental health score, being sexually active, current cigarette use, illicit drug use, not using seat belts, bullying, being bullied with a weapon, carrying a weapon, spending more time with friends, poor school image and physical abuse were found to be associated with fighting. Violent behaviour is common in high school students. There is a strong need for violence prevention programmes in schools.


Determination of correct implant size in radial head arthroplasty to avoid overlengthening.
Insertion of a radial head implant that results in radial overlengthening has been associated with altered elbow kinematics, increased radiocapitellar joint forces, capitellar erosions, early-onset arthritis, and loss of elbow flexion. The purpose of this study was to identify clinical and radiographic features that may be used to diagnose overlengthening of the radius intraoperatively and on postoperative radiographs. Radial head implants of varying thicknesses were inserted into seven cadaver specimens, which were then assessed clinically and radiographically. Eight stages were examined: the intact specimen (stage 1); repair of the lateral collateral ligament (stage 2); radial head resection with repair of the lateral collateral ligament (stage 3); insertion of an implant of the correct thickness (stage 4); and insertion of an implant that resulted in radial overlengthening of 2 mm (stage 5), 4 mm (stage 6), 6 mm (stage 7), or 8 mm (stage 8). The specimens were tested with and without muscle loading to simulate resting muscle tone and surgical paralysis, respectively. At each stage, radiographs were made to measure the ulnohumeral joint space and the lateral ulnohumeral joint was visually assessed. We identified no difference, with regard to medial ulnohumeral joint incongruity as seen radiographically, among stages 1 through 6 during the tests with muscle loading. A significant difference in medial ulnohumeral joint incongruity was found in stages 7 (p = 0.003) and 8 (p < 0.001). The clinical (visually assessed) lateral ulnohumeral joint space gap was negligible in stages 1 through 4 but increased significantly at all stages involving overlengthening (gross gap, 0.9 mm with 2 mm of overlengthening [p = 0.005], 2.3 mm with 4 mm of overlengthening [p < 0.001], 3.4 mm with 6 mm [p < 0.001], and 4.7 mm with 8 mm [p < 0.001]). Incongruity of the medial ulnohumeral joint becomes apparent radiographically only after overlengthening of the radius by >or=6 mm. Intraoperative visualization of a gap in the lateral ulnohumeral joint is a reliable indicator of overlengthening following the insertion of a radial head prosthesis.


Antiviral treatment for treatment-naïve chronic hepatitis B: systematic review and network meta-analysis of randomized controlled trials.
Chronic hepatitis B (CHB) infection poses a significant burden to public health worldwide. Most cases are clinically silent until late in the disease course. The main goal of current therapy is to improve survival and quality of life by preventing disease progression to cirrhosis and liver failure, and consequently hepatocellular carcinoma development. The objective of this review is to provide a contemporary and comprehensive evaluation of the effectiveness of treatment options. We performed a systematic review of peer-reviewed literature for randomized controlled trials involving treatment-naïve CHB adult population who received antiviral therapy. The endpoints were virologic response (VR), normalization of alanine aminotransferase (ALT norm), HBeAg loss, HBeAg seroconversion, and HBsAg loss for the HBeAg-positive population; and VR and ALT norm for the HBeAg-negative population. Network meta-analysis (NMA) was performed to synthesize evidence on the efficacy of treatment. Forty-two publications were selected. Twenty-three evaluated HBeAg-positive population, 13 evaluated HBeAg-negative population, and six evaluated both. We applied NMA to the efficacy outcomes of the two populations separately. Treatment strategies were ranked by the probability of achieving outcomes, and pairwise comparisons calculated from NMA were reported in odds ratios (OR). For HBeAg-positive population, tenofovir disoproxil fumarate (TDF) and tenofovir alafenamide (TAF) were the best for VR; OR vs adefovir = 14.29, 95% CI 7.69-25 and 12.5, 95% CI 4.35-33.33 respectively. TAF was the best for achieving ALT norm (OR vs placebo = 12.5, 95% CI 4.55-33.33), HBeAg loss, and seroconversion (OR vs entecavir/TDF combination = 3.03, 95% CI 1.04-8.84 and 3.33, 95% CI 1.16-10 respectively). In the HBeAg-negative population, TDF and TAF were the best for VR (OR vs adefovir = 9.79, 95% CI 2.38-42.7 and 11.71, 95% CI 1.03-150.48 respectively). Telbivudine and TAF were the best for ALT norm. Certain nucleos(t)ide combinations also had high probability of achieving positive outcomes. Our results are consonant with current clinical guidelines and other evidence reviews. For both HBeAg-positive and HBeAg-negative populations, TDF and TAF are the most effective agents for virologic suppression, and TAF is effective across all outcomes.


Characterizing biogeochemical fluctuations in a world of extremes: A synthesis for temperate intertidal habitats in the face of global change.
Coastal and intertidal habitats are at the forefront of anthropogenic influence and environmental change. The species occupying these habitats are adapted to a world of extremes, which may render them robust to the changing climate or more vulnerable if they are at their physiological limits. We characterized the diurnal, seasonal and interannual patterns of flux in biogeochemistry across an intertidal gradient on a temperate sandstone platform in eastern Australia over 6 years (2009-2015) and present a synthesis of our current understanding of this habitat in context with global change. We used rock pools as natural mesocosms to determine biogeochemistry dynamics and patterns of eco-stress experienced by resident biota. In situ measurements and discrete water samples were collected night and day during neap low tide events to capture diurnal biogeochemistry cycles. Calculation of pHT using total alkalinity (TA) and dissolved inorganic carbon (DIC) revealed that the mid-intertidal habitat exhibited the greatest flux over the years (pHT 7.52-8.87), and over a single tidal cycle (1.11 pHT units), while the low-intertidal (pHT 7.82-8.30) and subtidal (pHT 7.87-8.30) were less variable. Temperature flux was also greatest in the mid-intertidal (8.0-34.5°C) and over a single tidal event (14°C range), as typical of temperate rocky shores. Mean TA and DIC increased at night and decreased during the day, with the most extreme conditions measured in the mid-intertidal owing to prolonged emersion periods. Temporal sampling revealed that net ecosystem calcification and production were highest during the day and lowest at night, particularly in the mid-intertidal. Characterization of biogeochemical fluctuations in a world of extremes demonstrates the variable conditions that intertidal biota routinely experience and highlight potential microhabitat-specific vulnerabilities and climate change refugia.


High resolution 4D HPCH experiment for sequential assignment of (13)C-labeled RNAs via phosphodiester backbone.
The three-dimensional structure determination of RNAs by NMR spectroscopy requires sequential resonance assignment, often hampered by assignment ambiguities and limited dispersion of (1)H and (13)C chemical shifts, especially of C4'/H4'. Here we present a novel through-bond 4D HPCH NMR experiment involving phosphate backbone where C4'-H4' correlations are resolved along the (1)H3'-(31)P spectral planes. The experiment provides high peak resolution and effectively removes ambiguities encountered during assignments. Enhanced peak dispersion is provided by the inclusion of additional (31)P and (1)H3' dimensions and constant-time evolution of chemical shifts. High spectral resolution is obtained by using non-uniform sampling in three indirect dimensions. The experiment fully utilizes the isotopic (13)C-labeling with evolution of C4' carbons. Band selective (13)C inversion pulses are used to achieve selectivity and prevent signal dephasing due to the C4'-C3' and C4'-C5' homonuclear couplings. Multiple quantum line narrowing is employed to minimize sensitivity loses. The 4D HPCH experiment is verified and successfully applied to a non-coding 34-nt RNA consisting typical structure elements and a 14-nt RNA hairpin capped by cUUCGg tetraloop.


Brain energy metabolism in Alzheimer's disease: 99mTc-HMPAO SPECT imaging during verbal fluency and role of astrocytes in the cellular mechanism of 99mTc-HMPAO retention.
The central hypothesis of the study which has been carried out as part of the NRP38 program, is that perturbations of brain energy metabolism are critically involved in the neurodegeneration occurring in Alzheimer's disease (AD) and that they may correlate with early cognitive dysfunctioning. In the present multidisciplinary study we set out to monitor brain energy metabolism using FDG-PET and HMPAO-SPECT imaging in a cohort of individuals over 65 years of age, drawn from the general population. HMPAO-SPECT imaging, which is a simpler and more widely accessible imaging procedure than FDG-PET, was performed under basal conditions and during the performance of a cognitive task (verbal fluency test). Three groups were studied. Two groups (groups I and II) included individuals age 65 or more, with no cognitive impairment and carrying an APOE4 positive or APOE4 negative phenotype, respectively; a third group (group III) included patients with clinical signs of AD. Each subject entering the study underwent an FDG-PET, an HMPAO-SPECT and an extensive battery of neuropsychological tests which assess various aspects of cognitive functioning, with a strong emphasis on working memory, divided attention and executive functions. A total of 101 participants were submitted to brain imaging and neuropsychological testing. Among these, 60 participants received the same set of imaging and neuropsychological tasks 24-36 months after the first set (phase II). In this article, we present a preliminary analysis performed on ten subjects from groups I and II and nine subjects from group III: activation (verbal fluency task) induced a specific pattern of increase in HMPAO retention (including BA 9/10, BA 18 bilaterally and right BA 17). In contrast to controls, in nine AD subjects no significant differences in HMPAO retention were observed when comparing activation and basal conditions. The cellular and molecular mechanisms that underlie the retention of HMPAO, the tracer used for single photon emission computed tomography (SPECT) imaging, has been studied in vitro in purified preparations of neurons and astrocytes with the aim of investigating the contribution of different cell types to hexamethyl-propyleneamineoxime labeled with technetium-99m (99mTc-HMPAO) retention in vitro. Results show that 99mTc-HMPAO retention predominates in astrocytes over neurons by a factor of approximately 2.5. Diethyl maleate, ethacrynic acid and buthionine sulfoximine, three agents which significantly reduce glutathione levels, also decreased 99mTc-HMPAO retention in both astrocytes and in neurons. Decrease did not always correlate with glutathione levels however, thus suggesting that other factors could be involved. The data presented indicate that astrocytes might constitute a prominent site of 99mTc-HMPAO retention and most likely contribute significantly to the SPECT signal. In addition, they also suggest that specific alterations in glial cell metabolism could explain flow-independent changes in 99mTc-HMPAO retention in the brain as observed by SPECT in certain pathologies (including Alzheimer's disease). In particular, these observations suggest a key role of astrocytes in the signal detected with the imaging procedure, which is altered in the Alzheimer's cohort subjected to the verbal fluency activation task.


Pulmonary necrotizing granulomas of unknown cause: clinical and pathologic analysis of 131 patients with completely resected nodules.
The cause of pulmonary necrotizing granulomas is often unclear, even after histologic examination. Our aim was to determine the clinical significance of histologically unexplained necrotizing granulomas. Pulmonary necrotizing granulomas surgically resected at the Mayo Clinic (1994-2004) were retrieved and reviewed retrospectively. Cases in which a cause was evident at the time of initial histologic examination were excluded. The analysis cohort comprised 131 completely resected histologically unexplained pulmonary necrotizing granulomas. Clinical and laboratory information was abstracted from medical records, chest CT scans were reviewed, histologic slides were reexamined, and additional ancillary studies were performed in selected cases. A cause was determined on review in more than one-half of the histologically unexplained necrotizing granulomas (79 of 131, 60%) by reexamining histologic slides (47), incorporating the results of cultures (26), fungal serologies (14), and other laboratory studies (eight), and correlating histologic findings with clinical and radiologic information (13). Infections accounted for the majority (64 of 79), the most common being histoplasmosis (37) and nontuberculous mycobacterial infections (18). Noninfectious diagnoses (15 of 79) were rheumatoid nodule (five), granulomatosis with polyangiitis (Wegener) (five), sarcoidosis (four), and chronic granulomatous disease (one). Many cases remained unexplained even after extensive review (52 of 131, 40%). Most of these patients received no medical therapy and did not progress clinically or develop new nodules (median follow-up, 84 months). A cause, the most common being infection, can be established in many surgically resected pulmonary necrotizing granulomas that appear unexplained at the time of initial histologic diagnosis. Patients whose granulomas remain unexplained after a rigorous review have a favorable outcome. Most do not develop new nodules or progress clinically, even without medical therapy.


Determinants of disability after lower extremity fracture.
Factors influencing the progression of physical impairment to patient-perceived disability are not well known. We sought to better understand this relationship in the setting of injury. We followed a cohort of 302 patients with lower extremity fractures over a 1-year period. Physical impairment was assessed by range of motion, strength, and pain. Range of motion and strength were assessed together as a proportion of normal function of the extremity (impairment score). Pain was assessed using a Visual Analogue Scale (VAS) pain score. Disability was assessed using the Sickness Impact Profile (SIP), a widely used measure of patient-perceived limitations of everyday activities attributable to illness. The SIP was administered during hospitalization to assess preinjury baseline. Impairment assessment and readministration of the SIP were performed at 12 months after injury. Impairment in leg function (range of motion and strength) was highly correlated (p < 0.001) with overall SIP score at 12 months, but accounted for only 23% of the variance in overall SIP scores. Likewise, VAS pain score was highly correlated (p < 0.001) with overall SIP score at 12 months, but accounted for only 29% of the variance in overall SIP scores. In a multivariate linear regression analysis, variables that were independently associated with overall SIP score included impairment score, VAS pain score, preinjury SIP, poverty status, education status, social support, having hired a lawyer, and involvement with workers' compensation. These variables accounted for 52% of the variance in overall SIP scores at 12 months. The degree of physical impairment accounts for only a small amount of the variance in disability from lower extremity fracture. Identifiable patient characteristics including age, socioeconomic status, preinjury health, and social support together with impairment account for over half of the variance in long-term disability. Further research is needed to increase understanding of other factors that influence the progression of impairment to disability, especially those factors that may be amenable to intervention.


A wireless MEMS-based inclinometer sensor node for structural health monitoring.
This paper proposes a wireless inclinometer sensor node for structural health monitoring (SHM) that can be applied to civil engineering and building structures subjected to various loadings. The inclinometer used in this study employs a method for calculating the tilt based on the difference between the static acceleration and the acceleration due to gravity, using a micro-electro-mechanical system (MEMS)-based accelerometer. A wireless sensor node was developed through which tilt measurement data are wirelessly transmitted to a monitoring server. This node consists of a slave node that uses a short-distance wireless communication system (RF 2.4 GHz) and a master node that uses a long-distance telecommunication system (code division multiple access-CDMA). The communication distance limitation, which is recognized as an important issue in wireless monitoring systems, has been resolved via these two wireless communication components. The reliability of the proposed wireless inclinometer sensor node was verified experimentally by comparing the values measured by the inclinometer and subsequently transferred to the monitoring server via wired and wireless transfer methods to permit a performance evaluation of the wireless communication sensor nodes. The experimental results indicated that the two systems (wired and wireless transfer systems) yielded almost identical values at a tilt angle greater than 1°, and a uniform difference was observed at a tilt angle less than 0.42° (approximately 0.0032° corresponding to 0.76% of the tilt angle, 0.42°) regardless of the tilt size. This result was deemed to be within the allowable range of measurement error in SHM. Thus, the wireless transfer system proposed in this study was experimentally verified for practical application in a structural health monitoring system.


Sonographic evaluation of jugulodigastric and juguloomohyoid lymph nodes.
The jugulodigastric (JD) and juguloomohyoid (JO) lymph nodes are levels II and III cervical lymph nodes corresponding to the upper and middle internal jugular chains, respectively. The aim of this study is to delineate the sonographic properties of these two nodes, which are commonly encountered in routine neck sonography, in subjects with normal neck ultrasound findings. Atypical findings can make it difficult to differentiate benign from malignant lymph nodes. The JD and JO lymph nodes of 126 subjects were examined by ultrasonography, and size, shape, presence of echogenic hilus and Doppler activity were recorded. Among the lymph nodes examined, 31.6% were not elliptical. Proportionally more of the JO than the JD nodes were round; there was a significant difference in roundness index between them (P < 0.05). An echogenic hilus was demonstrated in 223 of the 252 JD nodes and in 161 of the 252 JO nodes. Significantly more of the lymph nodes with roundness index <2 lacked a visible echogenic hilus. There was a positive correlation between the visibility of an echogenic hilus and Doppler activity. Normal jugulodigastric and juguloomohyoid lymph nodes are relatively prominent in the upper and middle jugular chains, respectively. Awareness of variations in the sonographic appearance of these nodes could preclude unnecessary procedures. Clin. Anat. 29:943-948, 2016. © 2016 Wiley Periodicals, Inc.


A biochemical rationale for the discrete behavior of nitroxyl and nitric oxide in the cardiovascular system.
The redox siblings nitroxyl (HNO) and nitric oxide (NO) have often been assumed to undergo casual redox reactions in biological systems. However, several recent studies have demonstrated distinct pharmacological effects for donors of these two species. Here, infusion of the HNO donor Angeli's salt into normal dogs resulted in elevated plasma levels of calcitonin gene-related peptide, whereas neither the NO donor diethylamine/NONOate nor the nitrovasodilator nitroglycerin had an appreciable effect on basal levels. Conversely, plasma cGMP was increased by infusion of diethylamine/NONOate or nitroglycerin but was unaffected by Angeli's salt. These results suggest the existence of two mutually exclusive response pathways that involve stimulated release of discrete signaling agents from HNO and NO. In light of both the observed dichotomy of HNO and NO and the recent determination that, in contrast to the O2/O2- couple, HNO is a weak reductant, the relative reactivity of HNO with common biomolecules was determined. This analysis suggests that under biological conditions, the lifetime of HNO with respect to oxidation to NO, dimerization, or reaction with O2 is much longer than previously assumed. Rather, HNO is predicted to principally undergo addition reactions with thiols and ferric proteins. Calcitonin gene-related peptide release is suggested to occur via altered calcium channel function through binding of HNO to a ferric or thiol site. The orthogonality of HNO and NO may be due to differential reactivity toward metals and thiols and in the cardiovascular system, may ultimately be driven by respective alteration of cAMP and cGMP levels.


Melanoma in people aged 65 and over in Scotland, 1979-89.
Detailed analysis of primary cutaneous melanoma first diagnosed in Scotland in patients aged 65 and over. Comparison of changing incidence, sex distribution, site, histogenetic type, tumour thickness, and prognosis of all primary cutaneous melanomas in patients aged 65 and over diagnosed in Scotland in the 11 years 1979-89 with similar data for patients aged under 65. Data were obtained from the Scottish Melanoma Group's database, established in 1979, which aims to record detailed clinical, pathological, and surgical follow up details of all primary cutaneous melanomas registered in Scotland. 1430 patients (954 women, 476 men) aged 65 and over; comprising over a third of the 3903 patients with primary melanoma recorded for all age groups in Scotland during this period. The overall incidence of melanoma in patients aged 65 and over increased from 12.2/100,000 in 1979 to 20.7/100,000 in 1989, with the greatest increase seen in older men, from 7.8/100,000 in 1979 to 18.0/100,000 in 1989. The site most commonly affected was the face in both men and women (33% of all tumours). The most common histogenetic type was superficial spreading melanoma. 526 patients (37%) had melanomas with a tumour thickness of 3.5 mm or greater in the older age group, compared with 453 patients (18%) in those aged under 65. The highest proportion of thick tumours was seen in older men. Five year survival figures for 616 patients diagnosed between 1979 and 1984 were 88%, 66%, and 47% for thin, intermediate, and thick tumours respectively. Overall five year survival for the older age group was 64% compared with 78% for the younger age group. The increase in melanoma in the elderly and the high proportion of thick tumours, especially in men, require a specific educational programme for both primary and secondary prevention directed towards the older population.


Estimating the environmental impacts of 57,000 food products.
Understanding and communicating the environmental impacts of food products is key to enabling transitions to environmentally sustainable food systems [El Bilali and Allahyari, Inf. Process. Agric. 5, 456-464 (2018)]. While previous analyses compared the impacts of food commodities such as fruits, wheat, and beef [Poore and Nemecek, Science 360, 987-992 (2018)], most food products contain numerous ingredients. However, because the amount of each ingredient in a product is often known only by the manufacturer, it has been difficult to assess their environmental impacts. Here, we develop an approach to overcome this limitation. It uses prior knowledge from ingredient lists to infer the composition of each ingredient, and then pairs this with environmental databases [Poore and Nemecek Science 360, 987-992 (2018); Gephart et al., Nature 597, 360-365 (2021)] to derive estimates of a food product's environmental impact across four indicators: greenhouse gas emissions, land use, water stress, and eutrophication potential. Using the approach on 57,000 products in the United Kingdom and Ireland shows food types have low (e.g., sugary beverages, fruits, breads), to intermediate (e.g., many desserts, pastries), to high environmental impacts (e.g., meat, fish, cheese). Incorporating NutriScore reveals more nutritious products are often more environmentally sustainable but there are exceptions to this trend, and foods consumers may view as substitutable can have markedly different impacts. Sensitivity analyses indicate the approach is robust to uncertainty in ingredient composition and in most cases sourcing. This approach provides a step toward enabling consumers, retailers, and policy makers to make informed decisions on the environmental impacts of food products.


Correlating the blood alcohol concentration with outcome after traumatic brain injury: too much is not a bad thing.
Although recent evidence suggests a beneficial effect of alcohol for patients with traumatic brain injury (TBI), the level of alcohol that confers the protective effect is unknown. Our objective was to investigate the relationship between admission blood alcohol concentration (BAC) and outcomes in patients with isolated moderate to severe TBI. From 2005 to 2009, the Los Angeles County Trauma Database was queried for all patients ≥14 years of age with isolated moderate to severe TBI and admission serum alcohol levels. Patients were then stratified into four levels based on admission BAC: None (0 mg/dL), low (0-100 mg/dL), moderate (100-230 mg/dL), and high (≥230 mg/dL). Demographics, patient characteristics, and outcomes were compared across levels. In evaluating 3794 patients, the mortality rate decreased with increasing BAC levels (linear trend P < 0.0001). In determining the relationship between BAC and mortality, multivariable logistic regression analysis demonstrated a high BAC level was significantly protective (adjusted odds ratio 0.55; 95% confidence interval: 0.38-0.8; P = 0.002). In the largest study to date, a high (≥230 mg/dL) admission BAC was independently associated with improved survival in patients with isolated moderate to severe TBI. Additional research is warranted to investigate the potential therapeutic implications.


Esthetic gingival recontouring--a plea for honesty.
There continues to be a tremendous amount of confusion in the dental literature and among practitioners regarding the diagnosis and treatment of gingival discontinuities. The purpose of this article is to present a rationale for gingival recontouring, illustrated by a case report. A patient requested gingival recontouring. Because the preoperative evaluation was inadequate, a simple gingivectomy procedure was performed. After healing, the tissue had rebounded to its preoperative levels. The patient was then evaluated more comprehensively, and gingival recontouring was accomplished with a mucoperiosteal flap and osseous recontouring. The tissue subsequently healed at the correct position and remained stable. To reliably perform gingival recontouring procedures, the dentist must have a clear understanding of the biologic width. By using diagnostic bone sounding, the practitioner can determine the appropriate surgical procedure that will ensure an esthetic and stable postoperative result.


The clinical effectiveness and cost-effectiveness of inhaled insulin in diabetes mellitus: a systematic review and economic evaluation.
To review the clinical effectiveness and cost-effectiveness of a new technology, the inhaled insulin, Exubera (Pfizer and Sanofi-Aventis, in collaboration with Nektar Therapeutics), a short-acting insulin. Electronic databases were searched up to November 2005. A systematic literature review was conducted and economic modelling carried out. An industry model was used for modelling. Nine trials of inhaled insulins were found, but only seven used the Exubera form of inhaled insulin. The other two used inhaled insulins that have not yet been licensed. There were five trials in type 1 and two in type 2 diabetes. Inhaled insulin is clinically effective, and is as good as short-acting soluble insulin in controlling blood glucose, plus it works slightly more quickly. None of the published trials compared it with short-acting analogues. Most patients in the trials were on combinations of short-acting, and either long- or intermediate-acting insulin, and both were changed, making it more difficult to assess the effects of only the change from soluble to inhaled insulin. Patient preference was the only significant difference between inhaled and soluble insulin in the trials. Most patients preferred inhaled to injected short-acting insulin, and this has some effect on quality of life measures. However, the control groups mostly used syringes and needles, rather than pens. As pens are more convenient, their use might have narrowed the patient satisfaction difference. There were no trials of inhaled insulin against continuous subcutaneous insulin infusion (CSII). No serious adverse experiences of inhaled insulin in the lung have been seen to date, but it is too soon yet to judge long-term effects. The manufacturer's model appears to be a high-quality one, although the results depend more on the assumptions fed into the model than on the model itself. The key assumptions are the size of the gain in quality of life utility from inhaling rather than injecting insulin, the effect of having an inhaled option on the willingness to start insulin among people with poor diabetic control on oral drugs, and the effect on glycaemic control. We consider that these assumptions make the cost-effectiveness appear better than it really would be. The manufacturer's submission assumed utility gains of 0.036-0.075 in patients with type 1 diabetes, and 0.027-0.067 in those with type 2, based on an unpublished utility elicitation study sponsored by the manufacturer. We thought that these gains were optimistic and that gains of 0.02 or less were more likely, on average. However, patients with particular problems with injection sites might have more to gain, although they might also be a group with much to gain from CSII. A key factor is the cost of inhaled insulin. Much more insulin has to be given by inhaler than by injection, and so the cost of inhaled insulin is much higher than injected. The extra cost depends on dosage but ranges from around 600 pounds to over 1000 pounds per patient per year. The inhaled insulin, Exubera, appears to be as effective, but no better than injected short-acting insulin. The additional cost is so much more that it is unlikely to be cost-effective. The long-term safety is uncertain. Additional research is recommended into the safety, efficacy and cost-effectiveness of inhaled insulin.


The application of perfluoroheteroaromatic reagents in the preparation of modified peptide systems.
The perfluoroheteroaromatic reagent pentafluoropyridine has proved to be a highly reactive electrophile, undergoing SNAr arylation reactions in the presence of a range of nucleophilic peptide side chains (i.e. cysteine, tyrosine, serine and lysine) under mild conditions. Moreover, we have shown how one-step peptide-modification using perfluoroheteroaromatics can deliver enhanced proteolytic stability in pharmaceutically-relevant peptides such as oxytocin.


A new efficient approach to fit stochastic models on the basis of high-throughput experimental data using a model of IRF7 gene expression as case study.
Mathematical models are used to gain an integrative understanding of biochemical processes and networks. Commonly the models are based on deterministic ordinary differential equations. When molecular counts are low, stochastic formalisms like Monte Carlo simulations are more appropriate and well established. However, compared to the wealth of computational methods used to fit and analyze deterministic models, there is only little available to quantify the exactness of the fit of stochastic models compared to experimental data or to analyze different aspects of the modeling results. Here, we developed a method to fit stochastic simulations to experimental high-throughput data, meaning data that exhibits distributions. The method uses a comparison of the probability density functions that are computed based on Monte Carlo simulations and the experimental data. Multiple parameter values are iteratively evaluated using optimization routines. The method improves its performance by selecting parameters values after comparing the similitude between the deterministic stability of the system and the modes in the experimental data distribution. As a case study we fitted a model of the IRF7 gene expression circuit to time-course experimental data obtained by flow cytometry. IRF7 shows bimodal dynamics upon IFN stimulation. This dynamics occurs due to the switching between active and basal states of the IRF7 promoter. However, the exact molecular mechanisms responsible for the bimodality of IRF7 is not fully understood. Our results allow us to conclude that the activation of the IRF7 promoter by the combination of IRF7 and ISGF3 is sufficient to explain the observed bimodal dynamics.


Clinical trials for lung cancer in China.
Lots of international multi-center clinical trials have been conducted in China over the past 10 years. We also have more and more clinical trials designed and launched by qualified Chinese investigators in recent years, especially after the establishment of the Chinese Thoracic Oncology Group (CTONG) in 2007. These trials are mainly about targeted drugs. The finished ones provided more evidence for the use of epidermal growth factor receptor tyrosine kinase inhibitors (EGFR-TKIs) in the first-line/maintenance/second-line settings in Chinese patients. The ongoing ones will diversify the use of EGFR-TKIs in 1(st)/2(nd)/3(rd) line settings and help to answer the questions whether patients will benefit from (neo)adjuvant EGFR-TKIs and chemotherapy intercalating and maintenance use of EGFR-TKIs. Here, we introduce far-reaching clinical trials conducted, ongoing and will be launched soon in China.


Subclinical thyroid disease.
The term subclinical thyroid disease is used to describe asymptomatic thyroid abnormalities found on imaging studies or laboratory tests. Thyroid nodules not palpable on physical examination but detected on imaging studies performed for other purposes are called incidentalomas. In the absence of risk factors for thyroid cancer, nodules that are less than 1 cm in diameter do not require biopsy. Subclinical hyperthyroidism is defined as suppressed serum sensitive thyrotropin (TSH) and normal serum thyroxine and triiodothyronine levels. This condition may adversely affect the heart and the bones and should be treated, especially in patients older than 60 years. Subclinical hypothyroidism, defined as mildly elevated serum TSH and normal serum thyroxine levels, is the most common thyroid dysfunction. In patients with subclinical hypothyroidism, thyroxine therapy should be given if the serum TSH level is higher than 10 mIU/L. For TSH values between 5 and 10 mIU/L, the decision for therapy should be individualized and depends on the level of TSH, presence of antithyroid antibodies, and clinical factors.


A Novel Evaluation Index and Optimization Method for Ankle Rehabilitation Robots Based on Ankle-Foot Motion.
The ability of ankle rehabilitation robots to accurately mimicking the actual human ankle motion is an important judgment basis for robot-assisted rehabilitation training. This paper proposes an evaluation index and mechanism parameter optimization method based on ankle-foot motion trajectory by exploring the human ankle-foot motion principle. First, the ankle UR equivalent model and a 3-degree-of-freedom (DOF) parallel ankle rehabilitation robot are described. Second, the ankle-foot motion data are measured by the body surface marker method, which proved the coupling of ankle-foot motion. Then, a new evaluation index, the ankle-foot motion comfort zone, is proposed, which is essentially the superimposed ankle-foot motion trajectory measured about 3-5 mm wide. Third, a mechanism parameter optimization method, is proposed in terms of the ankle-foot motion comfort zone as the evaluation index, which is applied to the 3-DOF parallel ankle rehabilitation robot, and the optimization results proved the feasibility of the method. Finally, the optimized rehabilitation robot is fitted with different ankle motions, and a prototype model is designed for kinematics simulation, which verifies the adaptability of the optimization method. This study provides a theoretical basis for the configuration design of ankle rehabilitation robots and provides a new direction for the optimization of the mechanism parameters.


Real-time PCR assays for genotyping of Cryptococcus gattii in North America.
Cryptococcus gattii has been the cause of an ongoing outbreak starting in 1999 on Vancouver Island, British Columbia and spreading to mainland Canada and the US Pacific Northwest. In the course of the outbreak, C. gattii has been identified outside of its previously documented climate, habitat, and host disease. Genotyping of C. gattii is essential to understand the ecological and geographical expansion of this emerging pathogen. We developed and validated a mismatch amplification mutation assay (MAMA) real-time PCR panel for genotyping C. gattii molecular types VGI-VGIV and VGII subtypes a,b,c. Subtype assays were designed based on whole-genome sequence of 20 C. gattii strains. Publically available multilocus sequence typing (MLST) data from a study of 202 strains was used for the molecular type (VGI-VGIV) assay design. All assays were validated across DNA from 112 strains of diverse international origin and sample types, including animal, environmental and human. Validation revealed each assay on the panel is 100% sensitive, specific and concordant with MLST. The assay panel can detect down to 0.5 picograms of template DNA. The (MAMA) real-time PCR panel for C. gattii accurately typed a collection of 112 diverse strains and demonstrated high sensitivity. This is a time and cost efficient method of genotyping C. gattii best suited for application in large-scale epidemiological studies.


Associations of maternal dietary inflammatory potential and quality with offspring birth outcomes: An individual participant data pooled analysis of 7 European cohorts in the ALPHABET consortium.
Adverse birth outcomes are major causes of morbidity and mortality during childhood and associate with a higher risk of noncommunicable diseases in adult life. Maternal periconception and antenatal nutrition, mostly focusing on single nutrients or foods, has been shown to influence infant birth outcomes. However, evidence on whole diet that considers complex nutrient and food interaction is rare and conflicting. We aim to elucidate the influence of whole-diet maternal dietary inflammatory potential and quality during periconceptional and antenatal periods on birth outcomes. We harmonized and pooled individual participant data (IPD) from up to 24,861 mother-child pairs in 7 European mother-offspring cohorts [cohort name, country (recruitment dates): ALSPAC, UK (1 April 1991 to 31 December 1992); EDEN, France (27 January 2003 to 6 March 2006); Generation R, the Netherlands (1 April 2002 to 31 January 2006); Lifeways, Ireland (2 October 2001 to 4 April 2003); REPRO_PL, Poland (18 September 2007 to 16 December 2011); ROLO, Ireland (1 January 2007 to 1 January 2011); SWS, United Kingdom (6 April 1998 to 17 December 2002)]. Maternal diets were assessed preconceptionally (n = 2 cohorts) and antenatally (n = 7 cohorts). Maternal dietary inflammatory potential and quality were ranked using the energy-adjusted Dietary Inflammatory Index (E-DII) and Dietary Approaches to Stop Hypertension (DASH) index, respectively. Primary outcomes were birth weight and gestational age at birth. Adverse birth outcomes, i.e., low birth weight (LBW), macrosomia, small-for-gestational-age (SGA), large-for-gestational-age (LGA), preterm and postterm births were defined according to standard clinical cutoffs. Associations of maternal E-DII and DASH scores with infant birth outcomes were assessed using cohort-specific multivariable regression analyses (adjusted for confounders including maternal education, ethnicity, prepregnancy body mass index (BMI), maternal height, parity, cigarettes smoking, and alcohol consumption), with subsequent random-effects meta-analyses. Overall, the study mothers had a mean ± SD age of 29.5 ± 4.9 y at delivery and a mean BMI of 23.3 ± 4.2 kg/m2. Higher pregnancy DASH score (higher dietary quality) was associated with higher birth weight [β(95% CI) = 18.5(5.7, 31.3) g per 1-SD higher DASH score; P value = 0.005] and head circumference [0.03(0.01, 0.06) cm; P value = 0.004], longer birth length [0.05(0.01, 0.10) cm; P value = 0.010], and lower risk of delivering LBW [odds ratio (OR) (95% CI) = 0.89(0.82, 0.95); P value = 0.001] and SGA [0.87(0.82, 0.94); P value < 0.001] infants. Higher maternal prepregnancy E-DII score (more pro-inflammatory diet) was associated with lower birth weight [β(95% CI) = -18.7(-34.8, -2.6) g per 1-SD higher E-DII score; P value = 0.023] and shorter birth length [-0.07(-0.14, -0.01) cm; P value = 0.031], whereas higher pregnancy E-DII score was associated with a shorter birth length [-0.06(-0.10, -0.01) cm; P value = 0.026] and higher risk of SGA [OR(95% CI) = 1.18(1.11, 1.26); P value < 0.001]. In male, but not female, infants higher maternal prepregnancy E-DII was associated with lower birth weight and head circumference, shorter birth length, and higher risk of SGA (P-for-sex-interaction = 0.029, 0.059, 0.104, and 0.075, respectively). No consistent associations were observed for maternal E-DII and DASH scores with gestational age, preterm and postterm birth, or macrosomia and LGA. Limitations of this study were that self-reported dietary data might have increased nondifferential measurement error and that causality cannot be claimed definitely with observational design. In this cohort study, we observed that maternal diet that is of low quality and high inflammatory potential is associated with lower offspring birth size and higher risk of offspring being born SGA in this multicenter meta-analysis using harmonized IPD. Improving overall maternal dietary pattern based on predefined criteria may optimize fetal growth and avert substantial healthcare burden associated with adverse birth outcomes.


Robotic microsurgical vasovasostomy and vasoepididymostomy: a prospective randomized study in a rat model.
Microsurgical vasovasostomy and vasoepididymostomy remain technically challenging procedures. Refinements in technique have continually improved patency and pregnancy rates for the 2 procedures in experienced hands. Advances in surgical robotics produced the Da Vinci robot (Intuitive Surgical, Inc., Sunnyvale, California) with motion reduction and no tremor, features that may improve outcomes in microsurgery. We report a randomized prospective study of vasoepididymostomy and vasovasostomy using the Da Vinci robot in rats. A total of 24 adult male Wistar rats underwent vasectomy through a midline abdominal incision. Two weeks later the animals were randomized to microsurgical multilayer vasovasostomy, longitudinal vasoepididymostomy or robotic vasovasostomy and vasoepididymostomy groups. Outcomes measured included surgical time, complications, patency and sperm granuloma formation at 9 weeks. Animals were sacrificed 9 weeks after microsurgery. There were no significant differences in complications among the groups. Robotic vasovasostomy was significantly faster than the conventional microsurgical technique (68.5 vs 102.5 minutes, p = 0.002). The robotic and microsurgical vasoepididymostomy groups did not differ significantly in time. Patency rates were 100% for the robotic vasovasostomy and vasoepididymostomy groups, and 90% in the microsurgical vasovasostomy and vasoepididymostomy groups. These differences were not significant. Sperm granulomas were found in 70% of microsurgical vasovasostomy anastomoses and 27% of robotic vasovasostomy anastomoses (p = 0.001). No significant difference in the sperm granuloma rate was found between the robotic or microsurgical vasoepididymostomy groups (42% and 50%, respectively, p = 0.37). To our knowledge we report the first randomized prospective study using the Da Vinci robot for microsurgery. We believe that the improved stability and motion reduction during microsurgical suturing with the robot helped achieve excellent patency rates for vasovasostomy and vasoepididymostomy. The robot may also allow experienced microsurgeons to perform microsurgical procedures in patients at remote locations where no experienced microsurgeons are available.


Integrated Molecular Characterization of the Lethal Pediatric Cancer Pancreatoblastoma.
Pancreatoblastoma is a rare pediatric pancreatic malignancy for which the molecular pathogenesis is not understood. In this study, we report the findings of an integrated multiomics study of whole-exome and RNA sequencing as well as genome-wide copy number and methylation analyses of ten pancreatoblastoma cases. The pancreatoblastoma genome was characterized by a high frequency of aberrant activation of the Wnt signaling pathway, either via somatic mutations of CTNNB1 (90%) and copy-neutral loss of heterozygosity (CN-LOH) of APC (10%). In addition, imprinting dysregulation of IGF2 as a consequence of CN-LOH (80%), gain of paternal allele (10%), and gain of methylation (10%) was universally detected. At the transcriptome level, pancreatoblastoma exhibited an expression profile characteristic of early pancreas progenitor-like cells along with upregulation of the R-spondin/LGR5/RNF43 module. Our results offer a comprehensive description of the molecular basis for pancreatoblastoma and highlight rational therapeutic targets for its treatment.Significance: Molecular genetic analysis of a rare untreatable pediatric tumor reveals Wnt/IGF2 aberrations and features of early pancreas progenitor-like cells, suggesting cellular origins and rational strategies for therapeutic targeting. Cancer Res; 78(4); 865-76. ©2017 AACR.


Brain activation for lexical decision and reading aloud: two sides of the same coin?
This functional magnetic resonance imaging study compared the neuronal implementation of word and pseudoword processing during two commonly used word recognition tasks: lexical decision and reading aloud. In the lexical decision task, participants made a finger-press response to indicate whether a visually presented letter string is a word or a pseudoword (e.g., "paple"). In the reading-aloud task, participants read aloud visually presented words and pseudowords. The same sets of words and pseudowords were used for both tasks. This enabled us to look for the effects of task (lexical decision vs. reading aloud), lexicality (words vs. nonwords), and the interaction of lexicality with task. We found very similar patterns of activation for lexical decision and reading aloud in areas associated with word recognition and lexical retrieval (e.g., left fusiform gyrus, posterior temporal cortex, pars opercularis, and bilateral insulae), but task differences were observed bilaterally in sensorimotor areas. Lexical decision increased activation in areas associated with decision making and finger tapping (bilateral postcentral gyri, supplementary motor area, and right cerebellum), whereas reading aloud increased activation in areas associated with articulation and hearing the sound of the spoken response (bilateral precentral gyri, superior temporal gyri, and posterior cerebellum). The effect of lexicality (pseudoword vs. words) was also remarkably consistent across tasks. Nevertheless, increased activation for pseudowords relative to words was greater in the left precentral cortex for reading than lexical decision, and greater in the right inferior frontal cortex for lexical decision than reading. We attribute these effects to differences in the demands on speech production and decision-making processes, respectively.


Evidence-based review of interventions for autism used in or of relevance to occupational therapy.
Occupational therapy practitioners are among the professionals who provide services to children and adults with autism spectrum disorder (ASD), embracing both leadership and supportive roles in service delivery. The study's primary aims were as follows: (1) to identify, evaluate, and synthesize the research literature on interventions for ASD of relevance to occupational therapy and (2) to interpret and apply the research literature to occupational therapy. A total of 49 articles met the authors' criteria and were included in the review. Six categories of research topics were identified, the first 3 of which are most closely related to occupational therapy: (1) sensory integration and sensory-based interventions; (2) relationship-based, interactive interventions; (3) developmental skill-based programs; (4) social cognitive skill training; (5) parent-directed or parent-mediated approaches; and (6) intensive behavioral intervention. Under each category, themes supported by research evidence and applicable to occupational therapy were defined. The findings have implications for intervention methods, communication regarding efficacious practices to professionals and consumers, and future occupational therapy research.


SeqTrim: a high-throughput pipeline for pre-processing any type of sequence read.
High-throughput automated sequencing has enabled an exponential growth rate of sequencing data. This requires increasing sequence quality and reliability in order to avoid database contamination with artefactual sequences. The arrival of pyrosequencing enhances this problem and necessitates customisable pre-processing algorithms. SeqTrim has been implemented both as a Web and as a standalone command line application. Already-published and newly-designed algorithms have been included to identify sequence inserts, to remove low quality, vector, adaptor, low complexity and contaminant sequences, and to detect chimeric reads. The availability of several input and output formats allows its inclusion in sequence processing workflows. Due to its specific algorithms, SeqTrim outperforms other pre-processors implemented as Web services or standalone applications. It performs equally well with sequences from EST libraries, SSH libraries, genomic DNA libraries and pyrosequencing reads and does not lead to over-trimming. SeqTrim is an efficient pipeline designed for pre-processing of any type of sequence read, including next-generation sequencing. It is easily configurable and provides a friendly interface that allows users to know what happened with sequences at every pre-processing stage, and to verify pre-processing of an individual sequence if desired. The recommended pipeline reveals more information about each sequence than previously described pre-processors and can discard more sequencing or experimental artefacts.


Simulation and visualization of material flows in sanitation systems for streamlined sustainability assessment.
New and alternative sanitation systems are increasingly discussed and find their way into implementation. However, discussions on sanitation concepts often are held in a rather emotional way. Furthermore, not all the available sanitation concepts might be known to the decision maker. The work presented here attempts to contribute to a good discussion and decision making process by compiling available technologies, by defining easy-to-implement criteria for a sustainability assessment method and by integrating these results into a simulation tool which allows to visualize the related resource fluxes (e.g. those on nutrients, such as N, P and K) and to analyse different sanitation options with regard to their capital and operational costs and with regard to environmental impact criteria such as greenhouse gas emissions. Whilst the calculations are to be considered as being approximate in their nature (due to uncertainties or lack of suitable input data), this tool allows the planners, with sometimes little modelling experience, to consider the characteristics of sanitation systems. Whilst starting from earlier work, such as Eawag's Sanitation Compendium and work on material flow analysis, work described in this contribution merges resource flux modelling, easy-to-use simulation and visualization and methods of life cycle assessment and life cycle costing. The simulation tool is freely available on https://www.ifak.eu/en/products/sampsons.


Does Ethnicity Influence Fractional Exhaled Nitric Oxide in Healthy Individuals?: A Systematic Review.
Fractional exhaled nitric oxide (Feno) is used clinically as a biomarker of eosinophilic airway inflammation. Awareness of the factors influencing Feno values is important for valid clinical interpretation. We undertook a systematic review of PubMed, Cochrane Library, Scopus, and Web of Science databases and reference lists of included articles to evaluate whether ethnicity influences Feno values, and to determine if this influence affects clinical interpretation according to current guidelines. We included all studies that performed online Feno measurements on at least 25 healthy, non-Caucasian individuals, and examined the effect of ethnicity on Feno. From 62 potential studies, 12 studies were included. One study recruited only children (< 12 years of age), six studies recruited children and/or adolescents, four studies recruited adults only, and a single study involved children, adolescents, and adults. In total, 16 different ethnic populations representing 11 ethnicities were studied. Ethnicity was considered a significant influencing factor in 10 of the included studies. We found the geometric mean Feno to be above the normal healthy range in two studies. We also identified five studies in which at least 5% of participants had Feno results above the age-specific inflammatory ranges. Ethnicity influences Feno values, and for some ethnic groups this influence likely affects clinical interpretation according to current guidelines. There is a need to establish healthy Feno reference ranges for specific ethnic groups to improve clinical application.


Impact of familiarity upon children's developing facial expression recognition.
The impact of personal familiarity upon children's developing emotion-processing has been largely ignored in previous research, yet may prove particularly important given the emotional salience of such stimuli and children's greater exposure to familiar others compared to strangers. We examined the impact of personal familiarity upon developing facial expression recognition (FER). Participants included 153 children, 4-15 years old. We employed dynamic expressions of five emotions (happy, sad, anger, fear, disgust), posed by familiar (parents, teachers) and unfamiliar identities. Accuracy improved with age for recognising sad and fear expressions, but not anger. Children tended to correctly recognise happiness and fear at lower intensities. The impact of familiarity on FER depended on emotion-category. Familiarity did not affect recognition of sad expressions, but children were less accurate at recognising anger, fear, and disgust in familiar individuals compared to strangers. Personal familiarity may exert a distracting effect on children's performance. Findings highlight the importance of incorporating different emotion-categories and familiarity when examining the development of FER. Clinical implications are discussed.


One-parameter class of uncertainty relations based on entropy power.
We use the concept of entropy power to derive a one-parameter class of information-theoretic uncertainty relations for pairs of conjugate observables in an infinite-dimensional Hilbert space. This class constitutes an infinite tower of higher-order statistics uncertainty relations, which allows one in principle to determine the shape of the underlying information-distribution function by measuring the relevant entropy powers. We illustrate the capability of this class by discussing two examples: superpositions of vacuum and squeezed states and the Cauchy-type heavy-tailed wave function.


Tumour-necrosis factor-A polymorphisms and gastric cancer risk: a meta-analysis.
Inflammation is one of the early phases in the development of gastric cancer. Therefore, several studies have examined the association of polymorphisms in tumour-necrosis factor-A gene (TNF-A) with gastric cancer risk. This meta-analysis reviews and summarises published evidence for these associations. Searching several databases yielded 24 independent studies that reported on the associations between TNF-A polymorphisms and gastric cancer risk. We analysed available data for the most commonly investigated polymorphisms: TNF-A -308G>A (23 studies), TNF-A -238G>A (9 studies), and TNF-A -857C>T (5 studies). Summary odds ratios (ORs) and 95% confidence intervals (95% CIs) were calculated in the random-effects model using the DerSimonian-Laird method. Q-statistic and I(2)-statistic were calculated to examine heterogeneity, and funnel plots were plotted to examine small study effects. The overall ORs (95% CIs) for AG and AA genotypes vs GG genotype for TNF-A -308 were 1.09 (0.94-1.27) and 1.49 (1.11-1.99), respectively. For TNF-A -238, the corresponding ORs (95% CIs) were 1.05 (0.84-1.33) and 1.25 (0.30-5.26), respectively. The overall ORs (95% CIs) for CT and TT genotypes (vs CC) for TNF-A -857 were 1.06 (0.89-1.27) and 1.57 (0.91-2.70), respectively. The statistically significant association between TNF-A -308GG and gastric cancer was limited to western populations. This association showed little heterogeneity (I(2)=0) and remained consistently strong when analyses were limited to anatomic and histologic subtypes of gastric cancer, or limited to studies in which genotype frequencies were in Hardy-Weinberg equilibrium, or limited to larger studies. These same subgroup analyses did not change results associated with other polymorphisms. In conclusion, TNF-A -308AA genotype was associated with a statistically significant increased risk of gastric cancer, whereas other studied polymorphisms were not. The association between TNF-A -857TT genotype and gastric cancer was near significant, and may become significant if more studies are published.


Nonlinear protein degradation and the function of genetic circuits.
The functions of most genetic circuits require a sufficient degree of cooperativity in the circuit components. Although mechanisms of cooperativity have been studied most extensively in the context of transcriptional initiation control, cooperativity from other processes involved in the operation of the circuits can also play important roles. In this work, we examine a simple kinetic source of cooperativity stemming from the nonlinear degradation of multimeric proteins. Ample experimental evidence suggests that protein subunits can degrade less rapidly when associated in multimeric complexes, an effect we refer to as "cooperative stability." For dimeric transcription factors, this effect leads to a concentration-dependence in the degradation rate because monomers, which are predominant at low concentrations, will be more rapidly degraded. Thus, cooperative stability can effectively widen the accessible range of protein levels in vivo. Through theoretical analysis of two exemplary genetic circuits in bacteria, we show that such an increased range is important for the robust operation of genetic circuits as well as their evolvability. Our calculations demonstrate that a few-fold difference between the degradation rate of monomers and dimers can already enhance the function of these circuits substantially. We discuss molecular mechanisms of cooperative stability and their occurrence in natural or engineered systems. Our results suggest that cooperative stability needs to be considered explicitly and characterized quantitatively in any systematic experimental or theoretical study of gene circuits.


Personalized medicine in screening for malignant disease: a review of methods and applications.
Personalized medicine (PM) is currently a hot topic in the professional world. It is often called the medicine of the future and has already achieved resounding success in the area of targeted therapy. Nevertheless, integration of the concepts of PM into routine clinical practice is slow. This review is intended to give an overview of current and potential applications of PM in oncology. PM could soon play a decisive role, especially in screening. The relevance of PM in screening was examined in the case of four common cancers (colorectal cancer, lung cancer, breast cancer, and prostate cancer). A literature search was performed. This showed that biomarkers in particular play a crucial role in screening. In summary, it can be emphasized that there are already numerous known promising biomarkers in malignant disease. This results in several possibilities for individualizing and revolutionizing screening.


Double switch operations: Should we perform physiologic or anatomic repair in congenitally corrected transposition of the great arteries.
The seeking for the optimal surgical treatment of congenitally corrected transposition of the great arteries (cTGA) is ongoing. Physiologic (conventional) repair approaches, leaving the morphologic right ventricle (MRV) on the systemic circulation side, cause systemic ventricle and tricuspid valve failure, particularly in the long-term. Double Switch operations (anatomic repair) were aimed to convert the morphologic left ventricle to systemic ventricle and MRV to pulmonic ventricle. Gradual improvement in the early and midterm results of double switch operations in the last 20 years rendered anatomic repair to become a preferred procedure. Thanks to the preservation of ventricular functions through anatomic repair, patients with congenitally cTGA may survive longer with normal/near normal functional capacity. However, studies with larger sample size and longer follow-up duration are required to establish a more definite judgement.


Mars Science Laboratory relative humidity observations: Initial results.
The Mars Science Laboratory (MSL) made a successful landing at Gale crater early August 2012. MSL has an environmental instrument package called the Rover Environmental Monitoring Station (REMS) as a part of its scientific payload. REMS comprises instrumentation for the observation of atmospheric pressure, temperature of the air, ground temperature, wind speed and direction, relative humidity (REMS-H), and UV measurements. We concentrate on describing the REMS-H measurement performance and initial observations during the first 100 MSL sols as well as constraining the REMS-H results by comparing them with earlier observations and modeling results. The REMS-H device is based on polymeric capacitive humidity sensors developed by Vaisala Inc., and it makes use of transducer electronics section placed in the vicinity of the three humidity sensor heads. The humidity device is mounted on the REMS boom providing ventilation with the ambient atmosphere through a filter protecting the device from airborne dust. The final relative humidity results appear to be convincing and are aligned with earlier indirect observations of the total atmospheric precipitable water content. The water mixing ratio in the atmospheric surface layer appears to vary between 30 and 75 ppm. When assuming uniform mixing, the precipitable water content of the atmosphere is ranging from a few to six precipitable micrometers. Atmospheric water mixing ratio at Gale crater varies from 30 to 140 ppmMSL relative humidity observation provides good dataHighest detected relative humidity reading during first MSL 100 sols is RH75.


Catch Plus thrombectomy device in acute stroke: initial evaluation.
To report our initial experience with the Catch Plus thrombectomy device (CPD) in patients with acute ischemic stroke (AIS). We retrospectively evaluated the procedural variables as well as the clinical and angiographic outcomes of patients with acute occlusion of a major intracranial artery in the anterior circulation who were treated with CPD at our center. Baseline characteristics (gender, age, comorbidities, cardiovascular risk factors, National Institutes of Health Stroke Scale (NIHSS) score, and vessel occlusion sites) of these patients were recorded. Thrombolysis in Cerebral Infarction (TICI) score, incidence of symptomatic and asymptomatic bleeding, and 90 day modified Rankin Scale (mRS) scores were evaluated as indicators of outcome. 38 patients with a mean age of 67.5 years were treated with CPD. Mean time from symptom onset to procedure initiation was 226.7 min. Recanalization (TICI 2b-3) was achieved in 27 patients (71.1%). The median NIHSS score on admission was 20. Rates of symptomatic and asymptomatic intracerebral hemorrhage were 7.9% and 13.2%, respectively. The 90 day clinical follow-up data were available for 37 patients. The 90 day mortality rate was 18.9%, and the 90 day clinically acceptable functional outcome (mRS score ≤2) rate was 43.2% (mRS score 0-3, 54.1%). Very distal thrombectomy involving the cortical arteries was performed on four patients without complications. Our initial experience suggests that mechanical thrombectomy with the CPD improves 90 day outcomes of patients with AIS by facilitating effective recanalization.


Translating Discharge Instructions for Limited English-Proficient Families: Strategies and Barriers.
Access to written hospital discharge instructions improves caregiver understanding and patient outcomes. However, nearly half of hospitals do not translate discharge instructions, and little is known about why. To identify barriers to and potential strategies for translating children's hospital discharge instructions. We conducted a mixed-methods, multimodal analysis. Data comprised closed- and open-ended responses to an online survey sent to Children's Hospital Association language services contacts (n = 31), an online environmental scan of Children's Hospital Association translation policies (n = 22), and county-level census data. We examined quantitative data using descriptive statistics and analyzed open-ended survey responses and written policies using inductive qualitative content analysis. Most survey respondents (81%) reported having a written translation policy at their hospital, and all reported translating a subset of hospital documents, for example, consent forms. Most but not all reported translating discharge instructions (74%). When asked how inpatient staff typically provide translated discharge instructions, most reported use of pretranslated documents (87%) or staff interpreters (81%). Reported barriers included difficulty translating uncommon languages, mismatched discharge and translation time frames, and inconsistent clinical staff use of translation services. Strategies to address barriers included document libraries, pretranslated electronic health record templates, staff-edited machine translations, and sight translation. Institutional policies differed regarding the appropriateness of allowing interpreters to assist with translation. Respondents agreed that machine translation should not be used alone. Children's hospitals experience similar operational and organizational barriers in providing language-concordant discharge instructions. Current strategies focus on translating standardized documents; collaboration and innovation may encourage provision of personalized documents.


Hyperexpression of α-hemolysin explains enhanced virulence of sequence type 93 community-associated methicillin-resistant Staphylococcus aureus.
The community-associated methicillin-resistant S. aureus (CA-MRSA) ST93 clone is becoming dominant in Australia and is clinically highly virulent. In addition, sepsis and skin infection models demonstrate that ST93 CA-MRSA is the most virulent global clone of S. aureus tested to date. While the determinants of virulence have been studied in other clones of CA-MRSA, the basis for hypervirulence in ST93 CA-MRSA has not been defined. Here, using a geographically and temporally dispersed collection of ST93 isolates we demonstrate that the ST93 population hyperexpresses key CA-MRSA exotoxins, in particular α-hemolysin, in comparison to other global clones. Gene deletion and complementation studies, and virulence comparisons in a murine skin infection model, showed unequivocally that increased expression of α-hemolysin is the key staphylococcal virulence determinant for this clone. Genome sequencing and comparative genomics of strains with divergent exotoxin profiles demonstrated that, like other S. aureus clones, the quorum sensing agr system is the master regulator of toxin expression and virulence in ST93 CA-MRSA. However, we also identified a previously uncharacterized AraC/XylS family regulator (AryK) that potentiates toxin expression and virulence in S. aureus. These data demonstrate that hyperexpression of α-hemolysin mediates enhanced virulence in ST93 CA-MRSA, and additional control of exotoxin production, in particular α-hemolysin, mediated by regulatory systems other than agr have the potential to fine-tune virulence in CA-MRSA.


Self-similar propagation of high-power parabolic pulses in optical fiber amplifiers.
Self-similarity techniques are used to study pulse propagation in a normal-dispersion optical fiber amplifier with an arbitrary longitudinal gain profile. Analysis of the nonlinear Schrödinger equation that describes such an amplifier leads to an exact solution in the high-power limit that corresponds to a linearly chirped parabolic pulse. The self-similar scaling of the propagating pulse in the amplifier is found to be determined by the functional form of the gain profile, and the solution is confirmed by numerical simulations. The implications for achieving chirp-free pulses after compression of the amplifier output are discussed.


Physical activity and stroke risk: a meta-analysis.
Whether physical activity reduces stroke risk remains controversial. We used a meta-analysis to examine the overall association between physical activity or cardiorespiratory fitness and stroke incidence or mortality. We searched MEDLINE from 1966 to 2002 and identified 23 studies (18 cohort and 5 case-control) that met inclusion criteria. We estimated the overall relative risk (RR) of stroke incidence or mortality for highly and moderately active individuals versus individuals with low levels of activity using the general variance-based method. The meta-analysis documented that there was a reduction in stroke risk for active or fit individuals compared with inactive or unfit persons in cohort, case-control, and both study types combined. For cohort studies, highly active individuals had a 25% lower risk of stroke incidence or mortality (RR=0.75; 95% CI, 0.69 to 0.82) compared with low-active individuals. For case-control studies, highly active individuals had a 64% lower risk of stroke incidence (RR=0.36; 95% CI, 0.25 to 0.52) than their low-active counterparts. When we combined both the cohort and case-control studies, highly active individuals had a 27% lower risk of stroke incidence or mortality (RR=0.73; 95% CI, 0.67 to 0.79) than did low-active individuals. We observed similar results in moderately active individuals compared with inactive persons (RRs were 0.83 for cohort, 0.52 for case-control, and 0.80 for both combined). Furthermore, moderately and highly active individuals had lower risk of both ischemic and hemorrhagic strokes than low-active individuals. We conclude that moderate and high levels of physical activity are associated with reduced risk of total, ischemic, and hemorrhagic strokes.


Temporal association of sNfL and gad-enhancing lesions in multiple sclerosis.
Multiple sclerosis (MS) is an autoimmune demyelinating disorder, which is characterized by relapses and remissions. Serum neurofilament light chain (sNfL) is an emerging biomarker of disease activity but its clinical use is still limited. In this study, we aim to characterize the temporal association between sNfL and new clinical relapses and new gadolinium-enhancing (Gd+) lesions. Annual sNfL levels were measured with a single-molecule array (SIMOA) assay in 94 patients with MS enrolled in the Comprehensive Longitudinal Investigation of Multiple Sclerosis at the Brigham and Women's Hospital (CLIMB) study. We used a multivariable linear mixed-effects model to test the temporal association of sNfL with clinical relapses and/or new Gd+ lesions. We adjusted this model for age, disease duration, sex, and disease-modifying therapies (DMTs) use. In the 3 months after a Gd+ lesion, we observed an average 35% elevation in sNfL (P < 0.0001) compared to remission samples. We also observed an average 32.3% elevation in sNfL at the time of or prior to a Gd+ lesion (P = 0.002) compared to remission. We observed a significant elevation in sNfL after a clinical relapse only when associated with a Gd+ lesion. Our findings support sNfL as a marker of clinical relapses and Gd+ lesions. sNfL peaks in a 3-month window around Gd+ lesions. sNfL shows promise as a biomarker of neurological inflammation and possibly of simultaneous Gd+ lesions during a clinical relapse.


Detection of simulated candidemia by the BACTEC 9240 system with plus aerobic/F and anaerobic/F blood culture bottles.
We studied the ability of the BACTEC 9240 automated blood culture system to detect simulated candidemia, including both Candida albicans and non-albicans Candida species. Simulated blood cultures were produced using 50 Candida isolates and BACTEC Plus Aerobic/F and Anaerobic/F blood culture bottles. Ten milliliters of blood and a suspension of each isolate containing 1,000 CFU were introduced into each bottle and then incubated at 35 degrees C in the BACTEC 9240 system. The system detected growth in 56 of 100 bottles. Four isolates did not have growth detected in either bottle after 21 days of incubation, resulting in four missed episodes of candidemia. If the blood culture bottles had been incubated for 5 days, an additional episode of candidemia would have remained undetected. If the bottles had been incubated for only 3 days, another episode would have been missed, resulting in up to six missed episodes of candidemia (four Candida glabrata isolates, one C. albicans isolate, and one Candida rugosa isolate). Terminal subculture of bottles without detected growth recovered yeast in 93% (41 of 44) of the bottles, representing 41 false negatives. In bottles where growth was detected, the time to detection was approximately 24 h. However, the mean time to growth detection for C. glabrata isolates in anaerobic medium was 22.14 +/- 2.47 h, but it was 120.89 +/- 35.33 h in aerobic medium (P < 0.001). The BACTEC 9240 system detected growth of most Candida isolates; however, the delayed time to detection of C. glabrata is clinically significant. Given the high rate of false negatives, terminal subcultures may be helpful in certain situations.


Increased contractile activity decreases RNA-protein interaction in the 3'-UTR of cytochrome c mRNA.
This study was designed to gain an insight into mechanisms by which cytochrome c gene expression is enhanced by increased contractile activity in skeletal muscle. When rat tibialis anterior muscles were stimulated (10 Hz, 0.25 ms) for 0, 2, 6, 12, or 24 h or 2, 5, 9, or 13 days (n = 4 for each time point), cytochrome c protein (enzyme-linked immunosorbent assay) and mRNA (Northern blot analysis) concentrations started to increase by 9 days, and this was associated with concurrent decreases in cytochrome c mRNA-protein interaction (RNA gel mobility shift assay). We found that the decreased RNA-protein interaction in the stimulated muscle extract was restored by ultracentrifugation (150,000 g, 1 h) in the supernatant fraction. The 150,000 g pellet fraction of stimulated muscle was capable of inhibiting the RNA-protein interaction in control tibialis anterior muscles. These results provide evidence of an inhibitory factor that is responsible for decreasing RNA-protein interaction in the 3'-untranslated region of cytochrome c mRNA in continuously stimulated muscle.


Upper gastrointestinal tract injury in patients receiving kayexalate (sodium polystyrene sulfonate) in sorbitol: clinical, endoscopic, and histopathologic findings.
Kayexalate (sodium polystyrene sulfonate) in sorbitol has been demonstrated to cause colonic necrosis in a subset of uremic patients who are administered the cation exchange resin for treatment of hyperkalemia. Upper gastrointestinal damage associated with Kayexalate in sorbitol is reported far less frequently, and the clinicopathologic spectrum of disease in cases with upper gastrointestinal damage has not been investigated previously. The authors studied the clinical, endoscopic, and histologic features of 11 patients with Kayexalate crystals in biopsies from the esophagus (n = 7), stomach (n = 6), and duodenum (n = 2). The endoscopic appearance was markedly abnormal in all 11 patients. The effects of the medication closely mimicked other endoscopic and radiologic diagnoses in three cases, including esophageal carcinoma, Candidal esophagitis, and gastric bezoar. Histologic and/or endoscopic evidence of mucosal injury in the form of an ulcer or erosion was present in nine patients (82%). In four patients with mucosal injury, no other etiology apart from Kayexalate in sorbitol could be identified. In comparison with a cohort of patients with Kayexalate crystals in lower gastrointestinal specimens identified during the same period (11 patients) the frequency of associated mucosal damage was not significantly different (55%, p = 0.19), but no patient with upper gastrointestinal Kayexalate required surgical resection or died as a result of Kayexalate-induced mucosal injury. The results of this study provide evidence that Kayexalate in sorbitol can induce damage to the upper gastrointestinal tract. Recognition of Kayexalate crystals in histologic sections as a marker for sorbitol-induced mucosal damage may aid in establishing the correct diagnosis for clinically or endoscopically misleading lesions.


Longitudinal Investigation of Depression, Intimate Partner Violence, and Supports Among Vulnerable Families.
Intimate partner violence (IPV) affects nearly 12 million individuals and their families each year in the United States. Many negative outcomes are associated with IPV, with depression being one of the most prevalent mental health problems. Most previous studies on IPV have used cross-sectional designs to examine the potential protective effects of support on depression. The current study fills this gap by conducting a longitudinal investigation of the roles of social support and family resources on depression among caregivers of young children. The study sample consisted of 548 female caregivers. Findings suggest that among those with an IPV history, those with higher social support reported lower depressive symptoms than those with less social support. No significant interaction was found for family resources and IPV. Rather, family resources had a main effect on depressive symptoms with no differential impact based on IPV status. Findings suggest the importance of connecting vulnerable families to supports such as social support and family resources to help mitigate depressive symptoms. Future research should consider the underlying mechanisms of social support as a protective factor among IPV victims with depression.


Digitized patient-provider interaction: How does it matter? A qualitative meta-synthesis.
Sociological interest in the digitization of health has predominantly been studied using qualitative approaches. Research in this field has grown steadily since the late 1990's but to date, no synthesis has been conducted to integrate this now rather comprehensive corpus of data. In this paper we present a meta-ethnography of 15 papers reporting qualitative studies of digitally mediated patient - professional interactions. By dissecting the detailed descriptions of digitized practices in this most basic relationship in health care, we explore how these studies can illuminate important aspects of social relations in contemporary society. Our interpretative synthesis enables us to reassert a sociological view that places changes in social structures and interaction at the core of questions about the digitization of health care. Our synthesis of this literature identifies four key concepts that point at structural processes of change. We argue that when patient-professional interactions are digitized, relations are respatialized, and there are reconnections of relational components. These lead to empirically specific reactions, which can be characterized as reconstitutions and renegotiations of social practices which in turn are related to the reconfiguration of basic social institutions. We propose a new direction for exploring the digitalization of health care to illuminate how digital health is related to contemporary social change.