Brewery wastewater treatment using MBR coupled with nanofiltration or electrodialysis: biomass acclimation and treatment efficiency.
Breweries release significant amounts of wastewater loaded with various organic and mineral materials. Prior studies of membrane bioreactor (MBR) wastewater treatment have been conducted with very little interest granted to the conditions of biomass acclimation. This study displays biomass behavior during brewery wastewater treatment by an aerobic MBR. In addition, nanofiltration and electrodialysis have been studied as potential post-treatment to decrease mineral concentrations and permit further water reuse for agriculture. An anoxic/aerobic laboratory MBR, associated with a flat sulfonated polyether membrane was used for synthetic brewery wastewater treatment. Biomass acclimation was performed using a feeding substrate. Organic concentrations in the MBR influent varied from 700 mg COD/L to 10,600 mg COD/L (COD: chemical oxygen demand) for 110 days. The results indicate a good acclimation to effluent with high salts and organic matter loads. Steady evolution of biomass concentration and activities was achieved after 90 days of operation. A reduction of COD of around 95% was obtained with MBR and up to 99% with nanofiltration post-treatment for the reconstructed brewery effluent with an organic loading rate of 7 g COD/L·d and a solid and hydraulic retention time of 30 days and 36 hours. A good reduction of the salt content was also recorded primarily with the nanofiltration and electrodialysis processes.


Social class and cause of death.
Previous studies have shown that causes of death differ in their relationship to social class, but we lack a more comprehensive description of this variation. The present study provides a detailed and extensive list of social class differences for a large number of specific causes of death. All deaths between 1991 and 2003 in Sweden were linked with information on household social class from 1990. Relative death risks and excess mortality in groups of causes according to the European shortlist were estimated separately for men and women in eight classes using Cox Regression. A clear mortality gradient among employees was found for the majority of causes, from low-relative death risks among higher managerial and professional occupations to relatively high risks for the unskilled working class. There is considerable variation in the strength of the association, from causes such as malignant melanoma, breast cancer and transport accidents among women, where no clear class differences were found. At the other extreme, mental and behavioural disorders, endocrine, nutritional and metabolic diseases and diseases of the respiratory system all show steep slopes for both men and women. Circulatory diseases and cancer together account for 15-20% of excess mortality. Exceptions to the general pattern--causes of death in which higher social classes are exposed to greater death risks or in which there is no mortality gradient--are practically non-existent. There is nevertheless significant variation in the strength of the class differences in specific causes.


Psychosocial adjustment in twin pairs with and without hemifacial microsomia.
To compare the psychosocial adjustment of children with and without hemifacial microsomia (HFM). This cross-sectional pilot study investigated psychosocial adjustment of twin pairs in which one twin was affected with HFM and the other was unimpaired. Data were analyzed using paired t tests. The dental medicine clinic of a large urban children's hospital, serving a multistate area. Participants were six twin pairs aged 9 to 15 years and their parents. Data were also collected from classroom teachers. Outcome measures included: the Child Behavior Checklist (CBCL), the Teacher Report Form (TRF), the Coopersmith Self-Esteem Inventory (SEI), and a structured self-concept interview (the Self-Interview). Children with HFM had significantly higher CBCL and TRF total behavior problem scores and lower SEI general self-esteem scores than their unimpaired twins. No differences were found in CBCL competence scores. Interview data revealed concerns among the HFM group related to appearance, negative social responses, and fear of hospital procedures. Children also reported positive aspects of coping with HFM. The results of this study suggest that, similar to other craniofacial conditions, HFM is associated with an elevated risk for childhood psychosocial difficulties. Replication of specific findings with a larger sample is needed. Multicenter, collaborative studies are a crucial next step for this field.


A new species of Sciurodendrium (Nematoda: Heligmonellidae) in Sciurus aureogaster (Rodentia: Sciuridae) from Morelos, Mexico.
Sciurodendrium bravohollisae n. sp. (Heligmonellidae) is described as an intestinal parasite of 2 squirrels, Sciurus aureogaster Cuvier, 1829, collected from Los Robles, Municipio de Tlalnepantla, Morelos State, Mexico. The new species differs from all other congeners in possessing a very well-developed and sacciform genital cone. This is the seventh species described for the genus and the first one recorded in Mexico.


[From gene to disease; Menkes disease: copper deficiency due to an ATP7A-gene defect].
Menkes disease is an X-linked recessive disorder characterized by neurological deterioration, failure to thrive, peculiar hair and death in childhood, secondary to mutations in the ATP7A gene. The ATP7A gene encodes for a copper transporting P-type ATPase (ATP7A), which is ubiquitously expressed. A defect of the ATP7A protein leads to both a reduced transport of copper from the intestine into the circulation and into the central nervous system, as well as reduced transport of copper into the Golgi apparatus for incorporation into various copper-dependent enzymes. This results in a systemic copper deficiency as well as reduced activity of various copper-dependent enzymes. The reduced activity of these copper-dependent enzymes accounts for most of the characteristic features ofMenkes disease patients.


Applications of free-electron lasers in the biological and material sciences.
Free-Electron Lasers (FELs) collectively operate from the terahertz through the ultraviolet range and via intracavity Compton backscattering into the X-ray and gamma-ray regimes. FELs are continuously tunable and can provide optical powers, pulse structures and polarizations that are not matched by conventional lasers. Representative research in the biological and biomedical sciences and condensed matter and material research are described to illustrate the breadth and impact of FEL applications. These include terahertz dynamics in materials far from equilibrium, infrared nonlinear vibrational spectroscopy to investigate dynamical processes in condensed-phase systems, infrared resonant-enhanced multiphoton ionization for gas-phase spectroscopy and spectrometry, infrared matrix-assisted laser-desorption-ionization and infrared matrix-assisted pulsed laser evaporation for analysis and processing of organic materials, human neurosurgery and ophthalmic surgery using a medical infrared FEL and ultraviolet photoemission electron microscopy for nanoscale characterization of materials and nanoscale phenomena. The ongoing development of ultraviolet and X-ray FELs are discussed in terms of future opportunities for applications research.


Adherence to antiretroviral therapy among HIV infected children measured by caretaker report, medication return, and drug level in Dar Es Salaam, Tanzania.
Adherence to antiretroviral drugs in the treatment of paediatric HIV infection is complicated because of many factors including stigma and drug intake logistics. It is therefore important to identify children with non-adherence in order to intervene before they become at risk of developing treatment failure or drug resistance. The aim of this study was to determine the level of adherence to antiretroviral therapy (ART), measured by caretaker report, medication return and nevirapine plasma concentration. In addition, the association between level of adherence and patient's immune status was compared across the three methods of measuring adherence. This was a descriptive cross-sectional study involving HIV infected children aged 2-14 years, on nevirapine- based antiretroviral treatment for at least six months, attending care and treatment clinic in three municipal hospitals in Dar- Es- Salaam City. Eligible patients and their accompanying caretakers were consecutively enrolled after obtaining written informed consent. Structured questionnaires were administered to caretakers to assess patient's adherence by caretaker report and medication return whereas a single blood sample for CD4 cell count/percent and determination of nevirapine plasma concentration was taken from patients on the day of assessment. A total of 300 patients and accompanying caretakers were enrolled and the mean patient age (SD) was 8 (3) years. Caretakers' report and medication return showed good adherence (98% and 97%) respectively. However, the level of adherence assessed by nevirapine plasma concentration (85%) was significantly lower than caretaker report and medication return (p < 0.001). The agreement between nevirapine plasma concentration and medication return and between nevirapine plasma concentration and caretaker report was weak (k = 0. 131) (k = 0. 09) respectively. Nevirapine plasma concentration below 3 μg/ml was associated with immunosuppression (p = 0. 021) whereas medication return (>5% of prescribed doses) and caretaker reported missing more than one dose within 72 hours prior to interview were not associated with immunosuppression (p = 0. 474), (p = 0. 569) respectively. Lower adherence level observed using nevirapine plasma concentration and its association with immunological response supports the validity of the method and indicates that adherence data obtained from caretaker report and medication return may overestimate the true adherence in paediatric antiretroviral therapy.


Prenatal and Postnatal PCB-153 and p,p'-DDE Exposures and Behavior Scores at 5–9 Years of Age among Children in Greenland and Ukraine.
Studies have reported some evidence of adverse effects of organochlorine exposures on child development, but the results have been inconsistent, and few studies have evaluated associations with child behavior. We investigated the association between prenatal and early-life exposures to 2,2',4,4',5,5'-hexachlorobiphenyl (PCB-153) and 1,1-dichloro-2,2-bis(p-chlorophenyl)-ethylene (p,p'-DDE) and behaviors in children between 5 and 9 y of age. In the Biopersistent organochlorines in diet and human fertility: Epidemiologic studies of time to pregnancy and semen quality in Inuit and European populations (INUENDO) cohort, consisting of mother-child pairs from Greenland and Ukraine (n=1,018), maternal serum PCB-153 and p,p'-DDE concentrations were measured during pregnancy, and cumulative postnatal exposures during the first 12 months after delivery were estimated using a pharmacokinetic model. Parents completed the Strengths and Difficulties Questionnaire (SDQ), and children's behaviors were dichotomized as abnormal (high) versus normal/borderline for five SDQ subscales and the total difficulties score. The total difficulties score, an overall measure of abnormal behavior, was not clearly associated with pre- or postnatal exposures to PCB-153 or to p,p'-DDE. However, pooled adjusted odds ratios (ORs) for high conduct problem scores with a doubling of exposure were 1.19 (95% CI: 0.99, 1.42) and 1.16 (95% CI: 0.96, 1.41) for pre- and postnatal PCB-153, respectively, and 1.25 (95% CI: 1.04, 1.51) and 1.24 (95% CI: 1.01, 1.51) for pre- and postnatal p,p'-DDE, respectively. Corresponding ORs for high hyperactivity scores were 1.24 (95% CI: 0.94, 1.62) and 1.08 (95% CI: 0.81, 1.45) for pre- and postnatal PCB-153, respectively, and 1.43 (95% CI: 1.06, 1.92) and 1.27 (95% CI: 0.93, 1.73) for pre- and postnatal p,p'-DDE, respectively. Prenatal and early postnatal exposures to p,p'-DDE and PCB-153 were associated with a higher prevalence of abnormal scores for conduct and hyperactivity at 5–9 y of age in our study population. These findings provide further support for the importance of minimizing organochlorine exposures to young children and to women of childbearing age. https://doi.org/10.1289/EHP553.


Left atrial emptying fraction predicts limited exercise performance in heart failure patients.
We aimed in this study to assess the role of left atrial (LA), in addition to left ventricular (LV) indices, in predicting exercise capacity in patients with heart failure (HF). This study included 88 consecutive patients (60 ± 10 years) with stable HF. LV end-diastolic and end-systolic dimensions, ejection fraction (EF), mitral and tricuspid annulus peak systolic excursion (MAPSE and TAPSE), myocardial velocities (s', e' and a'), LA dimensions, LA volume and LA emptying fraction were measured. A 6-min walking test (6-MWT) distance was performed on the same day of the echocardiographic examination. Patients with limited exercise performance (≤ 300 m) were older (p = 0.01), had higher NYHA functional class (p = 0.004), higher LV mass index (p = 0.003), larger LA (p = 0.002), lower LV EF (p = 0.009), larger LV end-systolic dimension (p = 0.007), higher E/A ratio (p = 0.03), reduced septal MAPSE (p < 0.001), larger LA end-systolic volume (p = 0.03), larger LA end-diastolic volume (p = 0.005) and lower LA emptying fraction (p < 0.001) compared with good performance patients. In multivariate analysis, only the LA emptying fraction [0.944 (0.898-0.993), p = 0.025] independently predicted poor exercise performance. An LA emptying fraction < 60% was 68% sensitive and 73% specific (AUC 0.73, p < 0.001) in predicting poor exercise performance. In heart failure patients, the impaired LA emptying function is the best predictor of poor exercise capacity. This finding highlights the need for routine LA size and function monitoring for better optimization of medical therapy in HF.


Degradation of annexin I in bronchoalveolar lavage fluid from patients with cystic fibrosis.
Annexin I is a 36 kilodalton (kD) calcium-dependent phospholipid-binding protein which may have anti-inflammatory properties. Previous investigations which sampled lower respiratory tract epithelial lining fluid (ELF) via bronchoalveolar lavage (BAL) have demonstrated that annexin I can be degraded in inflammatory lung disease. We analyzed BAL fluid from patients with cystic fibrosis (CF) to determine the effects of lung inflammation on the structure and activity of annexin I. Intact annexin I was absent in 17 out of 20 BAL fluid samples from patients with CF, due largely to degradation to a 33 kD protein. The three CF BAL fluids in which annexin I was detectable had very little or no unopposed neutrophil elastase activity in contrast to the 17 in which no annexin I was detectable. Annexin I was present in all BAL fluid samples from 10 normal volunteer (NV) subjects and 12 patients with interstitial lung disease (ILD). The 33 kD annexin I breakdown product was not detectable in samples from NV, but was detectable only in ILD patients with relatively high percentages of neutrophils on BAL differential cell counts. Annexin I appeared to be cleaved by neutrophil elastase at the N-terminal portion between Val-36 and Ser-37 to yield the 33 kD protein. Cleavage of the N-terminal portion of annexin I was accompanied by a marked change in the annexin I isoelectric point (pI) value (from 6.0 to 8.5-9.0) and greatly diminished annexin I functional activity. Our findings demonstrate that annexin I degradation in epithelial lining fluid is closely related to lung inflammation.


[The "two cultures" in medicine].
"The two cultures", a concept launched by C.P. Snow in 1959, points to the schism between science and the humanities, two distinct professional cultures which not only has gone separate ways, but also developed deep tensions between them. Historically, medicine is part of the scientific culture as well as that of the humanities. However, contemporary doctors see themselves first and foremost as scientists, and modern medicine leaves little scope for the tradition of the humanities. Including humanities in medical undergraduate, graduate and continuous education does not necessarily make doctors more humane, but insight in these disciplines may stimulate reflection and broaden their perspective on the practice of medicine. Given the expectations and pressures for efficiency to which doctors and other health care workers are subjected, a greater emphasis on the humanities in medicine may be of help to doctors in coping with their patients, society--and themselves.


Challenges to implementation of developmental screening in urban primary care: a mixed methods study.
Research is needed to identify challenges to developmental screening and strategies for screening in an urban pediatric setting. Parents of young children and clinicians at four urban pediatric practices participated in focus groups prior to implementation of screening. Participants were queried regarding attitudes, social norms, and barriers to developmental screening. Using information from the focus groups, workflow strategies were developed for implementing screening. Referral rates and satisfaction with screening were gathered at the conclusion. Six focus groups of parents and clinicians were conducted. Major themes identified included 1) parents desired greater input on child development and increased time with physicians, 2) physicians did not fully trust parental input, 3) physicians preferred clinical acumen over screening tools, and 4) physicians lacked time and training to conduct screening. For the intervention, developmental screening was implemented at the 9-, 18-, 24-, and 30-month well visits using the Ages & Stages Questionnaire-II and the Modified Checklist for Toddlers. 1397 (98% of eligible) children under 36 months old were enrolled, and 1184 (84%) were screened at least once. 1002 parents (85%) completed a survey at the conclusion of the screening trial. Most parents reported no difficulty completing the screens (99%), felt the screens covered important areas of child development (98%), and felt they learned about their child's strengths and limitations (88%). Developmental screening in urban low-income practices is feasible and acceptable, but requires strategies to capture parental input, provide training, facilitate referrals, and develop workflow procedures and electronic decision support.


Sodium-coupled neutral amino acid cotransporter inhibited by the volatile anesthetic, halothane, in megakaryocytes.
We have studied the effects of halothane, a popular volatile anesthetic, on Na(+)-coupled L-alanine cotransporters using rat bone marrow megakaryocytes subjected to patch-clamp whole-cell recordings. L-Alanine applied externally induced an immediate current response which was abolished by the elimination of external NaCl. The optical isomer, D-alanine, induced no such response. A ligand probe for the Na(+)-dependent amino-acid cotransporter (A-system), 2-methylaminoisobutyrate, induced a response comparable to that of L-alanine. The response was fitted by a Michaelis-Menten equation with a Km of 2.5 and 58.5 mM for L-alanine (with 120 mM Na+) and external Na+ (with 10 mM L-alanine), respectively. The volatile anesthetic, halothane, acutely and reversibly inhibited the inward current responsible for the Na(+)-coupled L-alanine cotransporter. Complete inhibition was attained at 1 mM, and 50%-inhibition at 0.35 mM. Halothane in a clinically relevant concentration reduced nutrient uptake via the cotransporter A-system. The sensitivity of the A-system to halothane is comparable to or greater than that of Na+/K+/Cl- cotransporter, sodium/proton exchange, stimulus-secretion coupling, and of many ion channels in nerve cells.


How climate impacts the composition of wolf-killed elk in northern Yellowstone National Park.
While the functional response of predators is commonly measured, recent work has revealed that the age and sex composition of prey killed is often a better predictor of prey population dynamics because the reproductive value of adult females is usually higher than that of males or juveniles. Climate is often an important mediating factor in determining the composition of predator kills, but we currently lack a mechanistic understanding of how the multiple facets of climate interact with prey abundance and demography to influence the composition of predator kills. Over 20 winters, we monitored 17 wolf packs in Yellowstone National Park and recorded the sex, age and nutritional condition of kills of their dominant prey-elk-in both early and late winter periods when elk are in relatively good and relatively poor condition, respectively. Nutritional condition (as indicated by per cent marrow fat) of wolf-killed elk varied markedly with summer plant productivity, snow water equivalent (SWE) and winter period. Moreover, marrow was poorer for wolf-killed bulls and especially for calves than it was for cows. Wolf prey composition was influenced by a complex set of climatic and endogenous variables. In early winter, poor plant growth in either year t or t - 1, or relatively low elk abundance, increased the odds of wolves killing bulls relative to cows. Calves were most likely to get killed when elk abundance was high and when the forage productivity they experienced in utero was poor. In late winter, low SWE and a relatively large elk population increased the odds of wolves killing calves relative to cows, whereas low SWE and poor vegetation productivity 1 year prior together increased the likelihood of wolves killing a bull instead of a cow. Since climate has a strong influence on whether wolves prey on cows (who, depending on their age, are the key reproductive components of the population) or lower reproductive value of calves and bulls, our results suggest that climate can drive wolf predation to be more or less additive from year to year.


Discounting of delayed rewards: Missing data imputation for the 21- and 27-item monetary choice questionnaires.
The Monetary Choice Questionnaire (MCQ) is a widely used behavioral task that measures the rate of delay discounting (i.e., k), the degree to which a delayed reward loses its present value as a function of the time to its receipt. Both 21- and 27-item MCQs have been extensively validated and proven valuable in research. Different methods have been developed to streamline MCQ scoring. However, existing scoring methods have yet to tackle the issue of missing responses or provide clear guidance on imputing such data. Due to this lack of knowledge, the present study developed and compared three imputation approaches that leverage the MCQ's structure and prioritize ease of implementation. Additionally, their performance was compared with mode imputation. A Monte Carlo simulation was conducted to evaluate the performance of these approaches in handling various missing responses in each observation across two datasets from prior studies that employed the 21- and 27-item MCQs. One of the three approaches consistently outperformed mode imputation across all performance measures. This approach involves imputing missing values using congruent non-missing responses to the items corresponding to the same k value or introducing random responses when congruent answers are unavailable. This investigation unveils a straightforward method for imputing missing data in the MCQ while ensuring unbiased estimates. Along with the investigation, an R tool was developed for researchers to implement this strategy while streamlining the MCQ scoring process.


Typical versus atypical presentation of obturator hernia.
Although it is a rare occurrence among all pelvic hernias diagnosed the obturator hernia continues to be a diagnostic challenge for surgeons today. These patients, who often have multiple concurrent medical problems, are subject to high morbidity and mortality rates resulting from late presentation and delayed surgical intervention. The vast majority of patients with obturator hernias are admitted with signs and symptoms of intestinal obstruction, namely anorexia, nausea, vomiting, constipation, and distension of 2 to 3 days' duration. In this paper, however, we highlight a small subset of obturator hernia patients who present without obstructive symptoms and do well after elective repair. The case reports that follow serve to compare and contrast two very different presentations of this surgical problem.


Calcium and vitamin D metabolism in Guamanian Chamorros with amyotrophic lateral sclerosis and parkinsonism-dementia.
We evaluated 16 Guamanian Chamorros with amyotrophic lateral sclerosis and 33 patients with parkinsonism-dementia for disturbances of calcium and vitamin D metabolism. The serum immunoreactive parathyroid hormone level was mildly elevated in 6 patients with amyotrophic lateral sclerosis and in 5 patients with parkinsonism-dementia. There were significant positive correlations between serum immunoreactive parathyroid levels and duration of illness in male patients with motor neuron disease, but not in female patients or in patients with parkinsonism-dementia. Intestinal absorption of calcium, as assessed by serum and urinary activity of calcium 47 following oral administration, was decreased in 2 patients with amyotrophic lateral sclerosis and in 4 patients with parkinsonism-dementia, all of whom had low levels of serum 1,25-dihydroxyvitamin D. Reductions in cortical bone mass were striking in patients with motor neuron disease. A significant negative correlation was found between the percentage of cortical area of the second metacarpal bone and muscle atrophy and weakness, and significant positive correlations were found between degree of immobility and ratio of urinary hydroxyproline to creatinine in patients with amyotrophic lateral sclerosis and parkinsonism-dementia. In general, abnormalities in calcium metabolism were subtle. Thus, if the demonstrated deposition of metals, particularly calcium and aluminum, in central nervous system tissues of Guamanians with these two conditions is a cause of the diseases and of the early appearance of neurofibrillary tangles in neurons, the accumulation has apparently occurred long before onset of symptoms, and detectable abnormalities of calcium and vitamin D metabolism may already have been corrected.


Isolation and growth of a Pseudomonas species that utilizes cyanide as a source of nitrogen.
A simple method of isolating bacteria that utilize cyanide as a source of nitrogen for growth has been developed. This involved supplying hydrogen cyanide as a vapour to glucose-containing minimal-salts agar plates. The bacteria isolated were Gram-negative, oxidase-positive rods producing a fluorescent green pigment and were tentatively identified as strains of Pseudomonas fluorescens. Three organisms were studied further and shown to be P. fluorescens biotype II. One of these (NCIB 11764) was grown in a glucose-containing fed-batch culture with either NH4Cl or KCN as the limiting nutrient. Cyanide-grown bacteria produced stoichiometric amounts of ammonia from cyanide when pulsed with cyanide under aerobic conditions. Stimulation of oxygen uptake was seen on addition of cyanide to suspensions of cyanide-grown but not ammonia-grown bacteria.


Topical Oxaliplatin Produces Gain- and Loss-of-Function in Multiple Classes of Sensory Afferents.
The platinum chemotherapeutic oxaliplatin produces dose-limiting pain, dysesthesia, and cold hypersensitivity in most patients immediately after infusion. An improved understanding of the mechanisms underlying these symptoms is urgently required to facilitate the development of symptomatic or preventative therapies. In this study, we have used skin-saphenous nerve recordings in vitro and behavioral experiments in mice to characterize the direct effects of oxaliplatin on different types of sensory afferent fibers. Our results confirmed that mice injected with oxaliplatin rapidly develop mechanical and cold hypersensitivities. We further noted profound changes to A fiber activity after the application of oxaliplatin to the receptive fields in the skin. Most oxaliplatin-treated Aδ- and rapidly adapting Aβ-units lost mechanical sensitivity, but units that retained responsiveness additionally displayed a novel, aberrant cold sensitivity. Slowly adapting Aβ-units did not display mechanical tachyphylaxis, and a subset of these fibers was sensitized to mechanical and cold stimulation after oxaliplatin treatment. C fiber afferents were less affected by acute applications of oxaliplatin, but a subset gained cold sensitivity. Taken together, our findings suggest that direct effects on peripheral A fibers play a dominant role in the development of acute oxaliplatin-induced cold hypersensitivity, numbness, and dysesthesia. PERSPECTIVE: The chemotherapeutic drug oxaliplatin rapidly gives rise to dose-limiting cold pain and dysesthesia. Here, we have used behavioral and electrophysiological studies of mice to characterize the responsible neurons. We show that oxaliplatin directly confers aberrant cold responsiveness to subsets of A-fibers while silencing other fibers of the same type.


baySeq: empirical Bayesian methods for identifying differential expression in sequence count data.
High throughput sequencing has become an important technology for studying expression levels in many types of genomic, and particularly transcriptomic, data. One key way of analysing such data is to look for elements of the data which display particular patterns of differential expression in order to take these forward for further analysis and validation. We propose a framework for defining patterns of differential expression and develop a novel algorithm, baySeq, which uses an empirical Bayes approach to detect these patterns of differential expression within a set of sequencing samples. The method assumes a negative binomial distribution for the data and derives an empirically determined prior distribution from the entire dataset. We examine the performance of the method on real and simulated data. Our method performs at least as well, and often better, than existing methods for analyses of pairwise differential expression in both real and simulated data. When we compare methods for the analysis of data from experimental designs involving multiple sample groups, our method again shows substantial gains in performance. We believe that this approach thus represents an important step forward for the analysis of count data from sequencing experiments.


Effects of Hot Stamping and Tempering on Hydrogen Embrittlement of a Low-Carbon Boron-Alloyed Steel.
The effects of hot stamping (HS) and tempering on the hydrogen embrittlement (HE) behavior of a low-carbon boron-alloyed steel were studied by using slow strain rate tensile (SSRT) tests on notched sheet specimens. It was found that an additional significant hydrogen desorption peak at round 65⁻80 °C appeared after hydrogen-charging, the corresponding hydrogen concentration (CHr) of the HS specimen was higher than that of the directed quenched (DQ) specimen, and subsequent low-temperature tempering gave rise to a decrease of CHr. The DQ specimen exhibited a comparatively high HE susceptibility, while tempering treatment at 100 °C could notably alleviate it by a relative decrease of ~24% at no expanse of strength and ductility. The HS specimen demonstrated much lower HE susceptibility compared with the DQ specimen, and tempering at 200 °C could further alleviate its HE susceptibility. SEM analysis of fractured SSRT surfaces revealed that the DQ specimen showed a mixed transgranular-intergranular fracture, while the HS and low-temperature tempered specimens exhibited a predominant quasi-cleavage transgranular fracture. Based on the obtained results, we propose that a modified HS process coupled with low-temperature tempering treatment is a promising and feasible approach to ensure a low HE susceptibility for high-strength automobile parts made of this type of steel.


Origins of the New Latino Underclass.
Over the past four decades, the Latino population of the United States was transformed from a small, ethnically segmented population of Mexicans in the southwest, Puerto Ricans in New York, and Cubans in Miami into a large national population dominated by Mexicans, Central Americans, and South Americans. This transformation occurred through mass immigration, much of it undocumented, to the point where large fractions of non-Caribbean Hispanics lack legal protections and rights in the United States. Rising illegality is critical to understanding the disadvantaged status of Latinos today. The unauthorized population began to grow after avenues for legal entry were curtailed in 1965. The consequent rise in undocumented migration enabled political and bureaucratic entrepreneurs to frame Latino migration as a grave threat to the nation, leading to a rising frequency of negative framings in the media, a growing conservative reaction, and increasingly restrictive immigration and border policies that generated more apprehensions. Rising apprehensions, in turn, further enflamed the conservative reaction to produce even harsher enforcement and more still more apprehensions, yielding a self-feeding cycle in which apprehensions kept rising even though undocumented inflows had stabilized. The consequent militarization of the border had the perverse effect of reducing rates of out-migration rather than inhibiting in-migration, leading to a sharp rise in net undocumented population and rapid growth of the undocumented population. As a result, a majority of Mexican, Central American, and South American immigrants are presently undocumented at a time when unauthorized migrants are subject to increasing sanctions from authorities and the public, yielding down-ward pressure on the status and well-being of Latinos in the United States.


Surface specialization of the capillary endothelium in the pecten oculi of the chicken, and their overt roles in pectineal haemodynamics and nutrient transfer to the inner neural retina.
The structure of the capillary endothelium in the pecten oculi of the domestic fowl was investigated by scanning and transmission electron microscopy. Scanning electron microscopy results demonstrated the existence of a vast array of irregular microplicae that projected from the luminal surface of the capillary endothelium. In between these microplicae were numerous crevices. The microplicae were closely packed and showed no preferred orientation regarding either the longitudinal or transverse plane of the capillaries. Transmission electron microscopy revealed the section profiles of the microplicae: their tortuity, branching, interdigitations and the magnitude of the crevices contained. The endothelial cytoplasm exhibited a few mitochondria and micropinocytotic vesicles. The apparent set-up of the luminal plasmalemmal infoldings seemed to be designed for effecting impedance to the pectineal blood flow and thereby facilitating passive permeation of blood-borne nutrients to the inner neural retina. The reasons of such passive transport operation mediated by the endothelial microplicae of the avian pecten oculi are discussed in the perspective of the existing literature.


The influence of nano-ZnO application methods on UV protective properties of cotton.
The influence of different application methods on UV protective properties of white and dyed cotton functionalized with ZnO nanoparticles (nano-ZnO) was investigated. The methods differ in application procedure, time of treatment and auxiliaries used in the treating bath. The ultraviolet protection factor (UPF) was determined for untreated and functionalized samples. The presence of nano-ZnO on fibres was investigated using scanning electron microscopy (SEM) and Fourier transform infrared spectroscopy (FTIR). The content of Zn was determined with energy-dispersive X-ray spectroscopy (EDS) and inductively coupled plasma mass spectrometry (ICP-MS). Dynamic light scattering (DLS) was used for particle size measurements in the prepared solutions. The results show that UV protection of cotton increases with a higher content and uniform distribution of nano-ZnO on the samples and that dyeing increases the loading capacity of cotton towards nano-ZnO. One of the methods (Method IV) gave remarkable results giving cotton an excellent UV protection whether it was dyed or not.


Public Perceptions of the Benefits and Risks of Newborn Screening.
Growing technological capacity and parent and professional advocacy highlight the need to understand public expectations of newborn population screening. We administered a bilingual (French, English) Internet survey to a demographically proportional sample of Canadians in 2013 to assess preferences for the types of diseases to be screened for in newborns by using a discrete choice experiment. Attributes were: clinical benefits of improved health, earlier time to diagnosis, reproductive risk information, false-positive (FP) results, and overdiagnosed infants. Survey data were analyzed with a mixed logit model to assess preferences and trade-offs among attributes, interaction between attributes, and preference heterogeneity. On average, respondents were favorable toward screening. Clinical benefits were the most important outcome; reproductive risk information and early diagnosis were also valued, although 8% disvalued early diagnosis, and reproductive risk information was least important. All respondents preferred to avoid FP results and overdiagnosis but were willing to accept these to achieve moderate clinical benefit, accepting higher rates of harms to achieve significant benefit. Several 2-way interactions between attributes were statistically significant: respondents were willing to accept a higher FP rate for significant clinical benefit but preferred a lower rate for moderate benefit; similarly, respondents valued early diagnosis more when associated with significant rather than moderate clinical benefit. Members of the public prioritized clinical benefits for affected infants and preferred to minimize harms. These findings suggest support for newborn screening policies prioritizing clinical benefits over solely informational benefits, coupled with concerted efforts to avoid or minimize harms.


Defensive chemicals of tawny crazy ants, Nylanderia fulva (Hymenoptera: Formicidae) and their toxicity to red imported fire ants, Solenopsis invicta (Hymenoptera: Formicidae).
Nylanderia fulva (Mayr) has been reported as being able to displace Solenopsis invicta Buren, one of the most aggressive invasive ants in the world. Like S. invicta, N. fulva use chemical secretions in their defense/offense, which may contribute to their observed superior competition ability. In this study, the defensive chemicals of N. fulva workers and their toxicity against S. invicta workers were investigated. Like other formicine ants, N. fulva workers produce formic acid in their poison glands and 2-ketones and alkanes in Dufour glands. Of these, undecane and 2-tridecanone are two principal compounds in the Dufour gland. Topical LD50 values of 2-tridecanone and undecane against S. invicta workers ranged from 18.51 to 24.67 μg/ant and 40.39 to 84.82 μg/ant, respectively. Undecane and 2-tridecanone had significantly higher contact toxicity than formic acid, whereas formic acid had significantly higher fumigation toxicity than undecane and 2-tridecanone. The combination of 2-tridecanone as a contact toxin and formic acid as a fumigant significantly decreased KT50 values when compared to those of individual compounds. N. fulva does not seem unique in terms of the chemistry of its defensive secretion as compared to other formicine ants. However, this ant contained more than two orders of magnitude of formic acid (wt/wt) than other formicine ants and one order of magnitude of 2-tridecanone than the common crazy ant, Paratrechina longicornis (Latreille). The quantity, rather than quality, of the chemical secretion may contribute to the superior competition ability of N. fulva.


Endothelial signal transduction system enhances neutrophil-induced pulmonary vascular permeability.
The mechanism by which stimulated polymorphonuclear leukocytes and neutrophils (PMNs) damage pulmonary vascular endothelium was investigated. The authors assessed the ability of unstimulated and mechanically stimulated PMNs to adhere to pulmonary endothelial cells and, thereby, alter pulmonary vascular permeability, measured as the pulmonary filtration coefficient (K) and haemodynamics. PMNs were stimulated by gentle agitation in a glass vial for 10 s. Perfusing lungs with the stimulated PMNs (n=6) resulted in significant accumulation of PMNs within the lungs, assessed by myeloperoxidase levels, and elicited a 4-fold increase in K and a 2-fold increase in pulmonary vascular resistance as compared to lungs perfused with unstimulated cells (n=6). The increases in K were completely blocked by GF109203X, a protein kinase C inhibitor (n=6); however, GF109203X only partially attenuated the increase in vascular resistance and had little effect on the accumulation of stimulated PMNs. An agonist of protein kinase C, phorbol myristate acetate, elicited dose dependent increases in both K and pulmonary vascular resistance even in the absence of PMNs (n=6). These findings indicate that the increases in pulmonary filtration coefficient and pulmonary vascular resistance induced by polymorphonuclear neutrophils result from endothelial cell injury mediated by activation of protein kinase C within the endothelial cells themselves.


Defective AP-3-dependent VAMP8 trafficking impairs Weibel-Palade body exocytosis in Hermansky-Pudlak Syndrome type 2 blood outgrowth endothelial cells.
Weibel-Palade bodies are endothelial secretory organelles that contain von Willebrand factor, P-selectin and CD63. Release of von Willebrand factor from Weibel-Palade bodies is crucial for platelet adhesion during primary hemostasis. Endosomal trafficking of proteins like CD63 to Weibel-Palade bodies during maturation is dependent on the adaptor protein complex 3 complex. Mutations in the AP3B1 gene, which encodes the adaptor protein complex 3 β1 subunit, result in Hermansky-Pudlak syndrome 2, a rare genetic disorder that leads to neutropenia and a mild bleeding diathesis. This is caused by abnormal granule formation in neutrophils and platelets due to defects in trafficking of cargo to secretory organelles. The impact of these defects on the secretory pathway of the endothelium is largely unknown. In this study, we investigated the role of adaptor protein complex 3-dependent mechanisms in trafficking of proteins during Weibel-Palade body maturation in endothelial cells. An ex vivo patient-derived endothelial model of Hermansky-Pudlak syndrome type 2 was established using blood outgrowth endothelial cells that were isolated from a patient with compound heterozygous mutations in AP3B1 Hermansky-Pudlak syndrome type 2 endothelial cells and CRISPR-Cas9-engineered AP3B1-/- endothelial cells contain Weibel-Palade bodies that are entirely devoid of CD63, indicative of disrupted endosomal trafficking. Hermansky-Pudlak syndrome type 2 endothelial cells have impaired Ca2+-mediated and cAMP-mediated exocytosis. Whole proteome analysis revealed that, apart from adaptor protein complex 3 β1, also the μ1 subunit and the v-SNARE VAMP8 were depleted. Stimulus-induced von Willebrand factor secretion was impaired in CRISPR-Cas9-engineered VAMP8-/-endothelial cells. Our data show that defects in adaptor protein complex 3-dependent maturation of Weibel-Palade bodies impairs exocytosis by affecting the recruitment of VAMP8.


Probabilistic models for capturing more physicochemical properties on protein-protein interface.
Protein-protein interactions play a key role in a multitude of biological processes, such as signal transduction, de novo drug design, immune responses, and enzymatic activities. It is of great interest to understand how proteins interact with each other. The general approach is to explore all possible poses and identify near-native ones with the energy function. The key issue here is to design an effective energy function, based on various physicochemical properties. In this paper, we first identify two new features, the coupled dihedral angles on the interfaces and the geometrical information on π-π interactions. We study these two features through statistical methods: a mixture of bivariate von Mises distributions is used to model the correlation of the coupled dihedral angles, while a mixture of bivariate normal distributions is used to model the orientation of the aromatic rings on π-π interactions. Using 6438 complexes, we parametrize the joint distribution of each new feature. Then, we propose a novel method to construct the energy function for protein-protein interface prediction, which includes the new features as well as the existing energy items such as dDFIRE energy, side-chain energy, atom contact energy, and amino acid energy. Experiments show that our method outperforms the state-of-the-art methods, ZRANK and ClusPro. We use the CAPRI evaluation criteria, Irmsd value, and Fnat value. On Benchmark v4.0, our method has an average Irmsd value of 3.39 Å and Fnat value of 62%, which improves upon the average Irmsd value of 3.89 Å and Fnat value of 49% for ZRANK, and the average Irmsd value of 3.99 Å and Fnat value of 46% for ClusPro. On the CAPRI targets, our method has an average Irmsd value of 3.56 Å and Fnat value of 42%, which improves upon the average Irmsd value of 4.27 Å and Fnat value of 39% for ZRANK, the average Irmsd value of 5.15 Å and Fnat value of 30% for ClusPro.


Chrysobalanus icaco L. extract for antiangiogenic potential observation.
Angiogenesis is an important process in several physiological situations and it is also implicated in the development of some diseases such as diabetes and cancer. This study investigated the antiangiogenic potential of Chrysobalanus icaco methanol extract in the chicken embrionary tissue. Clinical trials for cancer treatment using drugs based on this mechanism are already in progress. Chorioallantoic membrane model (CAM) of chicken embryos, with C. icaco methanol extract in plastic diskes was used. The results showed an average of 44% angiogenesis inhibition in CAM areas with the plant extract compared to the controls. The data indicate that C. icaco methanol extract reduce the formation of new blood vessels in chicken chorioallantoic membrane.


Quantitative proteomics of yeast post-Golgi vesicles reveals a discriminating role for Sro7p in protein secretion.
We here report the first comparative proteomics of purified yeast post-Golgi vesicles (PGVs). Vesicle samples isolated from PGV-accumulating sec6-4 mutants were treated with isobaric tags (iTRAQ) for subsequent quantitative tandem mass spectrometric analysis of protein content. After background subtraction, a total of 66 vesicle-associated proteins were identified, including known or assumed vesicle residents as well as a fraction not previously known to be PGV associated. Vesicles isolated from cells lacking the polarity protein Sro7p contained essentially the same catalogue of proteins but showed a reduced content of a subset of cargo proteins, in agreement with a previously shown selective role for Sro7p in cargo sorting.


PDGFRbeta and HIF-1alpha inhibition with imatinib and radioimmunotherapy of experimental prostate cancer.
The clinical application of radioimmunotherapy (RIT) as a single modality in the treatment of prostate cancer is held back because of poor tumor responses to RIT and unacceptable normal tissue toxicities. The purpose of reported here studies was to develop a multimodality approach to RIT of prostate cancer that includes imatinib, a potent PDGFRbeta inhibitor, and in the course of these studies to define the mechanism of imatinib effects on RIT. Hypothesized interactions between these two modalities depend on the reduction of tumor interstitial fluid pressure with the subsequent increase of (131)ICC49 uptake into the tumor, and the inhibition of HIF-1alpha resulting in the improved tumor radiosensitivity. Levels of HIF-1alpha, IGF-1, PDGF-BB, phospho-PDGFRbeta and VEGF in response to imatinib were examined in PC-3 human prostate adenocarcinoma cells in vitro and in xenografts. RIT was based on (131)ICC49 and it was augmented with imatinib. Although PDGFRbeta appears to be functional in PC-3 tumors, the effect of imatinib on the tumor interstitial fluid pressure was insignificant. PC-3 cells and PC-3 xenografts express constitutive HIF-1alpha, which was significantly inhibited by imatinib. Reduced levels of HIF-1alpha were accompanied by the notable suppression of IGF-1. Simultaneously the increase in tumor levels of mouse and human PDGF-BB was observed. Improved PC-3 responses to RIT+imatinib treatment were significant and lasted approximately two weeks. Tumor doubling times in mice treated with (131)ICC49+imatinib were 21.6 +/- 0.7 days compared to 17.2 +/- 0.5 days in (131)ICC49+PBS-treated control mice. Imatinib alone had no effect on the tumor growth. In conclusion, imatinib inhibits HIF-1alpha expression in PC-3 tumors and improves RIT, but it has no effect on VEGF indicating absence of anti-angiogenic effects. There is a significant time- and dose-dependent reduction in the expression of IGF-1 suggesting an alternative pathway of imatinib-regulated HIF-1alpha expression leading to the improved PC-3 responses to RIT.


Capsule depolymerase overexpression reduces Bacillus anthracis virulence.
Capsule depolymerase (CapD) is a gamma-glutamyl transpeptidase and a product of the Bacillus anthracis capsule biosynthesis operon. In this study, we examined the effect of modulating capD expression on B. anthracis capsule phenotype, interaction with phagocytic cells and virulence in guinea pigs. Transcriptional fusions of capD were made to the genes encoding heat-shock protein 60 (hsp60) and elongation factor Tu (EFTu), and to capA, a B. anthracis capsule biosynthesis gene. Translation signals were altered to improve expression of capD, including replacing the putative ribosome-binding site with a consensus sequence and the TTG start codon with ATG. CapD was not detected by immunoblotting in lysates from wild-type B. anthracis Ames but was detected in strains engineered with a consensus ribosome-binding site for capD. Strains overexpressing capD at amounts detected by immunoblotting were found to have less surface-associated capsule and released primarily lower-molecular-mass capsule into culture supernatants. Overexpression of capD increased susceptibility to neutrophil phagocytic killing and adherence to macrophages and resulted in reduced fitness in a guinea pig model of infection. These data suggest that B. anthracis may have evolved weak capD expression resulting in optimized capsule-mediated virulence.


Efficacy of a Web-Based Self-Management Enhancing Program for Patients with Rheumatoid Arthritis: Explorative Randomized Controlled Trial.
Web-based self-management enhancing programs have the potential to support patients with rheumatoid arthritis (RA) in their self-management; for example, improve their health status by increasing their self-efficacy or taking their prescribed medication. We developed a Web-based self-management enhancing program in collaboration with RA patients and professionals as co-designers on the basis of the intervention mapping framework. Although self-management programs are complex interventions, it is informative to perform an explorative randomized controlled trial (RCT) before embarking on a larger trial. This study aimed to evaluate the efficacy of a Web-based self-management enhancing program for patients with RA and identify outcome measures most likely to capture potential benefits. A multicenter exploratory RCT was performed with an intervention group and a control group. Both groups received care as usual. In addition, the intervention group received 12 months of access to a Web-based self-management program. Assessment occurred at baseline, 6 months, and 12 months. Outcome measures included self-management behavior (Patient Activation Measurement, Self-Management Ability Scale), self-efficacy (Rheumatoid Arthritis task-specific Self-Efficacy, Perceived Efficacy in Patient-Physician Interaction), general health status (RAND-36), focus on fatigue (Modified Pain Coping Inventory for Fatigue), and perceived pain and fatigue (Numeric Rating Scales). A linear mixed model for repeated measures, using the intention-to-treat principle, was applied to study differences between the patients in the intervention (n=78) and control (n=79) groups. A sensitivity analysis was performed in the intervention group to study the influence of patients with high (N=30) and low (N=40) use of the intervention. No positive effects were found regarding the outcome measurements. Effect sizes were low. Based on these results, it is not possible to conclude on the positive effects of the intervention or to select outcome measures to be regarded as the primary/main or secondary outcomes for a future trial. A process evaluation should be performed to provide more insight into the low compliance with and effectiveness of the intervention. This can determine for whom this sort of program will work and help to fine-tune the inclusion criteria. Netherlands Trial Register NTR4871; https://www.trialregister.nl/trial/4726.


The relationship of morphology and motor abilities to specific table tennis tasks in youngsters.
The aim of this research was to establish the relationship of certain basic motor abilities and morphological characteristics and efficacy in specific table tennis tasks. The research sample consisted of cadet category table tennis players (N = 101; aged 10.52 +/- 0.78 years, training experience 2.8 +/- 0.93 years). The participants were measured as they performed 24 motor tasks, along with 15 anthropometric measures and 3 specific table tennis tests. Indicators of the relationship between morphological characteristics and motor abilities, coupled with the results of the specific table tennis tests indicate that: a) subcutaneous fatty tissue on the lower extremities significantly limits the test results where movements involving fast changes in direction are required; b) subcutaneous abdominal adipose tissues have a positive influence on tasks demanding controlled and precise alternate bouncing of the ball; c) in general, a positive influence can be seen in the results of specific tests concerning the following motor abilities: arm coordination, agility, explosive arm power, movement frequency speed and repetitive leg power. The test used for a coordination assessment of the whole body revealed a negative influence on the success of performing specific tasks.


Nephron sparing surgery for renal tumors-comparison of off-clamp partial nephrectomy with hilar clamping.
Open partial nephrectomy (PN) is still considered gold standard procedure for T1 localized renal tumors. Conventional technique involves clamping of the renal artery with or without vein however, renal ischemia produces a certain level of damage to the kidneys. This study aims to investigate potential effect of off-clamp vs. hilar clamping PN on renal function. This is a retrospective cohort study of patients who underwent unilateral, open partial nephrectomy for renal tumors b/w January 2009 December 2016 at our institution. A total of 90 partial nephrectomies were performed of which 65 cases were eligible for analysis. Non clamping technique was used in 43 while clamp was applied in 22 patients. Variables studied were patients' demographics, clinical variables, the laterality, tumors size and location, R.E.N.A.L nephrometry score, blood loss, tumor histology and surgical margins. Patients' renal function (serum creatinine and eGFR) were determined pre-operatively, at 3 and 12 months follow up. Data was analyzed on SPSS v. 22. Both the groups were comparable with regards to pre-operative renal function. Mean radiological size of tumor was 4.71±1.31 and 3.81±1.0 (0.003) in two groups respectively. Mean R.E.N.A.L nephrometry score was 6.1±1.5 in off-clamp group compared to 7.05 ± 1.7 in clamp group (p=0.04). No statistically significant difference was found in operative duration, blood loss, positive surgical margins and intra/ peri-operative complications. At three months and one year, renal function was better preserved in non-clamp group compared to clamp group (p=0.001 and 0.007 respectively). Off clamp open partial nephrectomy is safe and feasible option leading to less decline in renal function.


Effective indium-doped zinc oxide buffer layer on silver nanowires for electrically highly stable, flexible, transparent, and conductive composite electrodes.
We demonstrate a flexible, transparent, and conductive composite electrode comprising silver nanowires (Ag NWs), and indium-doped zinc oxide (IZO) layers. IZO is sputtered onto an Ag NW layer, with the unique structural features of the resulting composite suitable as a flexible, transparent, conductive electrode. The IZO buffer layer prohibits surface oxidation of the Ag NW, and is thereby effective in preventing undesirable changes in electrical properties. The newly designed composite electrode is a promising alternative to conventional ITO films for the production of flexible and transparent electrodes to be applied in next-generation flexible electronic devices.


Plasma urate and Parkinson's disease in women.
Plasma urate has been consistently associated with a lower risk of Parkinson's disease in men, but it is less clear if this relation exists in women. Between 1990 and 2004, the authors conducted a nested case-control study among participants of the female-only Nurses' Health Study. In controls (n = 504), plasma urate was positively associated with age, body mass index, alcohol consumption, hypertension, and use of diuretics and was inversely associated with physical activity and postmenopausal hormone use, as expected. Mean urate levels were 5.04 mg/dL for cases (n = 101) and 4.86 mg/dL for controls (P = 0.17). The age-, smoking-, and caffeine-adjusted rate ratio comparing women in the highest (≥5.8 mg/dL) with those in the lowest (<4.0 mg/dL) quartile was 1.33 (95% confidence interval: 0.69, 2.57; P(trend) = 0.4). Further adjustment for body mass index, physical activity, history of hypertension, and postmenopausal hormone use did not change the results. Unlike in men, these findings do not support the hypothesis that urate is strongly associated with lower rates of Parkinson's disease among women.


Human-Object Interactions Are More than the Sum of Their Parts.
Understanding human-object interactions is critical for extracting meaning from everyday visual scenes and requires integrating complex relationships between human pose and object identity into a new percept. To understand how the brain builds these representations, we conducted 2 fMRI experiments in which subjects viewed humans interacting with objects, noninteracting human-object pairs, and isolated humans and objects. A number of visual regions process features of human-object interactions, including object identity information in the lateral occipital complex (LOC) and parahippocampal place area (PPA), and human pose information in the extrastriate body area (EBA) and posterior superior temporal sulcus (pSTS). Representations of human-object interactions in some regions, such as the posterior PPA (retinotopic maps PHC1 and PHC2) are well predicted by a simple linear combination of the response to object and pose information. Other regions, however, especially pSTS, exhibit representations for human-object interaction categories that are not predicted by their individual components, indicating that they encode human-object interactions as more than the sum of their parts. These results reveal the distributed networks underlying the emergent representation of human-object interactions necessary for social perception.


Size-dependent electrocatalytic reduction of CO2 over Pd nanoparticles.
Size effect has been regularly utilized to tune the catalytic activity and selectivity of metal nanoparticles (NPs). Yet, there is a lack of understanding of the size effect in the electrocatalytic reduction of CO2, an important reaction that couples with intermittent renewable energy storage and carbon cycle utilization. We report here a prominent size-dependent activity/selectivity in the electrocatalytic reduction of CO2 over differently sized Pd NPs, ranging from 2.4 to 10.3 nm. The Faradaic efficiency for CO production varies from 5.8% at -0.89 V (vs reversible hydrogen electrode) over 10.3 nm NPs to 91.2% over 3.7 nm NPs, along with an 18.4-fold increase in current density. Based on the Gibbs free energy diagrams from density functional theory calculations, the adsorption of CO2 and the formation of key reaction intermediate COOH* are much easier on edge and corner sites than on terrace sites of Pd NPs. In contrast, the formation of H* for competitive hydrogen evolution reaction is similar on all three sites. A volcano-like curve of the turnover frequency for CO production within the size range suggests that CO2 adsorption, COOH* formation, and CO* removal during CO2 reduction can be tuned by varying the size of Pd NPs due to the changing ratio of corner, edge, and terrace sites.


Picroside III Ameliorates Colitis in Mice: A Study Based on Colon Transcriptome and Fecal 16S Amplicon Profiling.
Picroside III (Pic), an iridoid glycoside derived from Picrorhiza scrophulariiflora, exhibits therapeutic potential in mending damage to the intestinal mucosa. This study aimed to explore Pic's regulatory impact on intestinal inflammation and the gut microbiota in mice with dextran sulfate sodium (DSS)-induced colitis. The findings revealed that pretreatment with Pic mitigated the DSS-induced escalation of the disease activity index (DAI), alleviated intestinal damage, and attenuated intestinal inflammation in mice. RNA-seq analysis, complemented by experimental validation, elucidated that Pic significantly hindered Akt phosphorylation in the colon tissues of colitis-afflicted mice. Furthermore, 16S rRNA sequencing demonstrated that Pic pretreatment effectively rectified microbial dysbiosis in colitis mice by elevating the abundance of Lactobacillus murinus and Lactobacillus gasseri. These observations suggest that Pic's efficacy in colitis treatment stems from its inhibition of intestinal inflammation via the suppression of the PI3K-Akt pathway and modulation of gut microbiota. This study contributes novel scientific insights into the potential application of Pic in the management of inflammatory bowel disease (IBD).


Sex diagnosis of subadult specimens from Medieval Polish archaeological sites: metric analysis of deciduous dentition.
The subject of this work is the characterisation of the metric features of deciduous dentition in a Medieval population of central Poland with the use of the jackknife technique leave one out (LOO)-supporting multivariate methods, which are important for deriving discrimination equations that would result in sex determination of children's skeletal remains. The sex of the individuals was assessed through analysis of sex-specific DNA sequences (AMELY/AMELX, SRY and alpha satellite sequences). Discriminant analysis concerned only teeth of those individuals whose sex was confirmed by the primary structure of three DNA sequences. The deciduous tooth diameters of males were found to be significantly larger than those of females in four respects: MD diameter of the maxillary second molar, MD and BL diameters of the mandibular first molar and BL diameter of the mandibular second molar. A two-group discriminant analysis considered all those measurements as independent variables. A multiple regression procedure produced a linear equation predicting the sex of children's skeletons with a significant probability amounting to approximately 78%. The accuracy of the sex assessment of an individual, using dental measurements, was established at 69% in deciduous male and 88% in deciduous female teeth.


Quantification of adaptive evolution of genes expressed in avian brain and the population size effect on the efficacy of selection.
Whether protein evolution is mainly due to fixation of beneficial alleles by positive selection or to random genetic drift has remained a contentious issue over the years. Here, we use two genomewide polymorphism data sets collected from chicken populations, together with divergence data from >5,000 chicken-zebra finch gene orthologs expressed in brain, to assess the amount of adaptive evolution in protein-coding genes of birds. First, we show that estimates of the fixation index (FI, the ratio of fixed nonsynonymous-to-synonymous changes over the ratio of the corresponding polymorphisms) are highly dependent on the character of the underlying data sets. Second, by using polymorphism data from high-frequency alleles, to avoid the confounding effect of slightly deleterious mutations segregating at low frequency, we estimate that about 20% of amino acid changes have been brought to fixation through positive selection during avian evolution. This estimate is intermediate to that obtained in humans (lower) and flies as well as bacteria (higher), and is consistent with population genetics theory that stipulates a positive relationship between the efficiency of selection and the effective population size. Further, by comparing the FIs for common and all alleles, we estimate that approximately 20% of nonsynonymous variation segregating in chicken populations represent slightly deleterious mutations, which is less than in Drosophila. Overall, these results highlight the link between the effective population size and positive as well as negative selection.


Serological identification of an Ir-region product.
Reciprocal immunization of congenic lines differing in the middle portion of the H-2 complex leads to the production of antibodies which react with an antigen or antigens controlled by the Ir region. The antigen designated Ir-1.1 seems to be present only on a subpopulation of lymphocytes from lymph nodes and spleen. It is absent on bone marrow cells.


Studies on the uptake and binding of propranolol by rat tissues.
The tissue distribution of propranolol after i.v. administration (1.5 and 7.5 mg/kg) was studied in rats. Lung, brain and kidney showed extensive propranolol tissue binding. Propranolol uptake by lung seemed to be a saturable process. In contrast to the above tissues, liver propranolol concentrations remained low over the time period of study. An increase in the propranolol T1/2 was noted at the high dose and seemed to result from reduced systemic clearance and an increase in the apparent volume of distribution. Microsomal and mitochondrial fractions from several tissues contained substantial amounts of propranolol after i.v. administration and in vitro incubation with homogenates. Cytosol proteins did not bind significant amounts of propranolol. Equilibrium dialysis studies with rat liver mitochondrial and microsomal fractions revealed both high affinity, low capacity propranolol binding sites and low affinity, high capacity sites. At low concentrations, propranolol interaction with rat liver microsomes produced a type I difference spectrum with high affinity binding of similar magnitude to that observed with equilibrium dialysis. Higher concentrations of propranolol produced a saturable shift in the difference spectra with reduced binding affinity for propranolol. Results from these studies indicate that particulate fractions from several tissues contribute to the extensive tissue binding of propranolol.


Accuracy of neuropathic pain measurements in patients with symptoms of polyneuropathy: validation of painDETECT, Self-Completed Leeds Assessment of Neuropathic Symptoms and Signs, and Douleur Neuropathique 4.
Pain is a common symptom in patients referred to polyneuropathy assessment. Diagnostic evaluation and choice of treatment may depend on whether the pain is likely to be neuropathic or not. This study aimed to investigate the diagnostic accuracy of 3 tools commonly used to differentiate between neuropathic and nonneuropathic pain. To accomplish this, we included patients with bilateral distal lower extremity pain, referred to neurological outpatient clinics at 5 Norwegian University hospitals for polyneuropathy assessment. The patients filled in Norwegian versions of painDETECT, the Self-Completed Leeds Assessment of Neuropathic Symptoms and Signs (S-LANSS), and the clinician-rated Douleur Neuropathique 4 (DN4). All patients underwent a clinical examination and nerve conduction measurements and were classified according to the NeuPSIG neuropathic pain criteria (reference standard). In total, 729 patients were included, of which 63% had neuropathic pain by the reference standard. Only DN4 demonstrated high sensitivity (0.87), whereas all 3 tools had low specificity (≤0.65). Importantly, the tools' predictive ability was unsatisfactory; The probability of getting a correct test result was 3 quarters at best, and at worst, no better than two fifths. Consequently, we show that neither DN4, painDETECT, nor S-LANSS can be confidently used to assess neuropathic pain in a neurological outpatient population with symptoms of polyneuropathy.


Insulin and contraction stimulate exocytosis, but increased AMP-activated protein kinase activity resulting from oxidative metabolism stress slows endocytosis of GLUT4 in cardiomyocytes.
Stimulations of glucose transport produced by insulin action, contraction, or through a change in cell energy status are mediated by separate signaling pathways. These are the wortmannin-sensitive phosphatidylinositol 3-kinase pathway leading to the intermediate Akt and the wortmannin-insensitive AMP-activated protein kinase (AMPK) pathway. Electrical stimulation of cardiomyocytes produced a rapid, insulin-like, wortmannin-sensitive stimulation of glucose transport activity, but this occurred without extensive activation of Akt. Although AMPK phosphorylation was increased by contraction, this response was not wortmannin-inhibitable and consequently did not correlate with the wortmannin sensitivity of the transport stimulation. Oxidative metabolism stress due to hypoxia or treatment with oligomycin led to increased AMPK activity with a corresponding increase in glucose transport activity. We show here that these separate signaling pathways converge on GLUT4 trafficking at separate steps. The rate of exocytosis of GLUT4 was rapidly stimulated by insulin, but insulin treatment did not alter the endocytosis rate. Like insulin stimulation, electrical stimulation of contraction led to a stimulation of GLUT4 exocytosis without any marked change in endocytosis. By contrast, after oxidative metabolism stress, no stimulation of GLUT4 exocytosis occurred; instead, this treatment led to a reduction in GLUT4 endocytosis.


The application of European system for cardiac operative risk evaluation II (EuroSCORE II) and Society of Thoracic Surgeons (STS) risk-score for risk stratification in Indian patients undergoing cardiac surgery.
To validate European system for cardiac operative risk evaluation II (EuroSCORE II) and Society of Thoracic Surgeons (STS) risk-score for predicting mortality and STS risk-score for predicting morbidity in Indian patients after cardiac surgery. EuroSCORE II and STS risk-scores were obtained pre-operatively for 498 consecutive patients. The patients were followed for mortality and various morbidities. The calibration of the scoring systems was assessed using Hosmer-Lemeshow test. The discriminative capacity was estimated by area under receiver operating characteristic (ROC) curves. The mortality was 1.6%. For EuroSCORE II and STS risk-score C-statics of 5.43 and 6.11 were obtained indicating satisfactory model fit for both the scores. Area under ROC was 0.69 and 0.65 for EuroSCORE II and STS risk-score with P values of 0.068 and 0.15, respectively, indicating poor discriminatory power. Good fit and discrimination was obtained for renal failure, long-stay in hospital, prolonged ventilator support and deep sternal wound infection but the scores failed in predicting risk of reoperation and stroke. Mortality risk was correctly estimated in low (< 2%) and moderate (2-5%) risk patients, but over-estimated in high-risk (> 5%) patients by both scoring systems. EuroSCORE II and STS risk-scores have satisfactory calibration power in Indian patients but their discriminatory power is poor. Mortality risk was over-estimated by both the scoring systems in high-risk patients. The present study highlights the need for forming a national database and formulating risk stratification tools to provide better quality care to cardiac surgical patients in India.


Role of T lymphocytes in adjuvant arthritis. I. Evidence for the regulatory function of thymus-derived cells in the induction of the disease.
Rats of Wistar King Aptekman (WKA) were thymectomized at 4 weeks of age and injected with Mycobacterium tuberculosis wax D 6 weeks after the operation to induce adjuvant arthritis. The development of this disease was strikingly enhanced by this treatment. Further experiments showed that a 4- to 6-week interval between thymectomy and wax D injection was necessary to show the enhancing effect. Such enhancement by thymectomy was also shown in rats of another strain, Sprague-Dawley (SD). The enhancing effect of thymectomy was abolished when thymocytes of normal syngeneic rats were transferred to thymectomized rats 7 days before the wax D inoculation. Furthermore, severe arthritis was also produced in WKA rats that were pretreated with low dose (200 R) whole body irradiation, but not in those treated with higher doses (400 to 700 R). These results seem to indicate that the enhancing effect is brought about by selective depletion of a certain population of T lymphocytes. The population depleted may be thymus dependent, short-lived and radiosensitive, the properties of which agree whith those known for suppressor T lymphocytes. Thus, it appears that thymus-derived cells could normally exert a regulatory effect on the development of adjuvant arthritis which might render these rat strains relatively less susceptible to this disease.


Clinical Effectiveness of Decision Support for Prescribing Opioids for Chronic Noncancer Pain: A Prospective Cohort Study.
This prospective cohort study examines the clinical effectiveness of electronic medical record clinical decision support (EMR CDS) for opioid prescribing. Data analysis included primary care patients with chronic opioid therapy for noncancer pain seen within an integrated health delivery system in Louisiana between January 2017 and October 2018. EMR CDS incorporated an opioid health maintenance tool to display the status of risk mitigation, and the medication order embedded the morphine equivalent daily dose (MEDD) calculator and a hyperlink to the Louisiana pharmacy drug monitoring program. Outcome measures included change in the average MEDD and rates of opioid risk mitigation, hospitalization, and emergency department use. Among 14 221 patients, 9% had prescriptions with an average MEDD ≥90 mg. There were no significant changes in MEDD after EMR CDS implementation. Increasing age, Charlson Comorbidity Index score, female sex, black non-Hispanic race, non-opioid pain medication co-prescriptions, and specialty referrals were associated with a lower odds of MEDD ≥90 (high-dose threshold). Medicare or self-pay, substance abuse history, and pain agreements were associated with increased odds of prescribing above this high-dose threshold. After incorporation of EMR CDS, patients had higher rates of urine drug screens (17% vs 7%) and naloxone prescriptions (3% vs 1%, all P < .001). In addition, specialty referrals to physical or occupational therapy, orthopedics, neurology, and psychiatry or psychology increased in the postintervention period. Although emergency department use decreased (rate ratio 0.92; 95% confidence interval 0.89-0.95), hospitalization rates did not change. EMR CDS improved adherence to opioid risk mitigation strategies. Further research examining which practice redesign interventions effectively reduce high-dose opioid prescribing is needed.


Memory, consciousness and neuroimaging.
Neuroimaging techniques that allow the assessment of memory performance in healthy human volunteers while simultaneously obtaining measurements of brain activity in vivo may offer new information on the neural correlates of particular forms of memory retrieval and their association with consciousness and intention. We consider evidence from studies with positron emission tomography and functional magnetic resonance imaging indicating that priming, a form of implicit retrieval, is associated with decreased activity in various cortical regions. We also consider evidence concerning the question of whether two components of explicit retrieval--intentional or effortful search and successful conscious recollection--are preferentially associated with increased activity in prefrontal and medial temporal regions, respectively. Last, we consider recent efforts to probe the relation between the phenomenological character of remembering and neural activity. In this instance we broaden our scope to include studies employing event-related potentials and consider evidence concerning the neural correlates of qualitatively different forms of memory, including memory that is specifically associated with a sense of self, and the recollection of particular temporal or perceptual features that might contribute to a rich and vivid experience of the past.


Sedative use and incident cognitive decline among persons aged 75 years and older: a population-based longitudinal study.
Acute exposure to sedative drugs may induce memory impairment, but there is mixed evidence that long-term sedative use may result in incident cognitive decline. The objective of this study was to investigate the use of sedative drugs and incident cognitive decline in a population-based sample of persons aged 75 years and older. The study sample comprised 781 participants in the Geriatric Multidisciplinary Strategy for the Good Care of the Elderly (GeMS) study in Kuopio, Finland. Data on health status, drug use, and sociodemographic factors were elicited during annual nurse interviews from 2004 to 2007. A linear mixed model was used to compare change in Mini-Mental State Examination (MMSE) scores (2005-2007) among users of sedative drugs in 2004 and 2005 (n = 139) to non-users of sedative drugs from 2004 to 2007 (n = 310). The model was adjusted for covariates including age, gender, education, depressive symptoms and antipsychotic use. Unadjusted mean MMSE scores were 27.50 in 2005, 26.58 in 2006, and 25.95 in 2007 among users of sedative drugs. Unadjusted mean MMSE scores were 28.05 in 2005, 27.61 in 2006, and 27.09 in 2007 among non-users of sedative drugs. Adjusted mean MMSE scores were 0.31 points lower in 2005, 0.62 points lower in 2006, and 0.93 lower in 2007 among users compared to non-users of sedative drugs (P = 0.051). Sedatives were not associated with statistically significant cognitive decline. However, clinicians should maintain a judicious approach to prescribing sedative drugs given the risk of adverse drug events.


Lack of Efficacy of the Neutropenic Diet in Decreasing Infections among Cancer Patients: A Systematic Review.
The objective of this systematic review is to evaluate the existing evidence supporting the effectiveness of the neutropenic diet in decreasing infection and mortality among cancer patients. We searched MEDLINE, EMBASE, Cochrane Central Register of Controlled Trials and Scopus for relevant articles published from database inception until March 2019. The Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA) guidelines were followed for this review. Individual studies were evaluated using the Oxford Center for Evidence-Based Medicine guidelines. A total of 473 articles were identified and 11 articles were selected after assessing eligibility. Our review showed that the neutropenic diet does not decrease infection rates or mortality among cancer patients. Currently, there is no uniform definition for the neutropenic diet across different institutions. For example, some institutions follow general food safety practices while others avoid foods that increase exposure to microbes and bacteria, and some follow both. Given these differences in practice regarding what constitutes a neutropenic diet, it is advisable that safe food handling and preparation practices recommended by the Food and Drug Administration be uniformly followed for neutropenic patients.


Tissue expanders in reconstructive surgery.
The shortage of skin and soft tissue has been the limiting factor in many reconstructive problems. Tissue expanders (a temporary inflatable device) were recently introduced, to provide the solution. In the first 25 patients of our series of patients age 7 years to 46 years, a total of 30 expanders were used in different parts of the body. The expanders used were made by Cox-Uphoff (CUI) and varied in size from 30 ml to 1000 ml, with an attached remote valve. These expanders were placed subcutaneously, subfascially or submuscularly. Expansion was carried out as an outpatient procedure over a period of 6 weeks. 21 of the 25 patients underwent successful treatment. Failures were due to technical problems, extrusion of expanders, haematoma and infection. Tissue expanders are a new dimension in reconstructive surgery. They cause stretching of skin and soft tissues over a period of time and permit resurfacing of skin defects in difficult situations. Complications may be avoided with experience and further refinements in the construction of the expanders.


Understanding the Complexities of Cirrhosis.
Cirrhosis and its related complications remain a prominent global health concern despite advances in understanding and treating the disorder. Early diagnosis and intervention strategies may reduce the impact of cirrhosis; however, it can be difficult for initial point-of-care health care providers to identify and refer patients with cirrhosis due to lack of knowledge and resources. This review examines current diagnostic strategies for cirrhosis and cirrhosis-related complications and the potential benefits of multidisciplinary care for patients with the disorder. A PubMed search of the medical literature was conducted to identify current diagnostic methods and standards and ascertain the impact of multidisciplinary care on patients with cirrhosis. Screening of patients at risk for cirrhosis has been recommended by several professional and governmental organizations. Unfortunately, identification of early-stage cirrhosis remains challenging despite development of novel calculations for risk (eg, aspartate transaminase-to-platelet count ratio) that use values from common, noninvasive laboratory tests to determine the extent of liver disease. Abnormal liver function test results and alterations in serum liver enzyme markers (eg, alanine and aspartate transaminases) may suggest cirrhosis in patients with chronic liver disease; however, they are not definitive. Liver biopsy is the gold standard for diagnosis and staging of cirrhosis, but its cost, invasiveness, and risk of complications have prompted the development of noninvasive tests (eg, elastography). Primary care physicians should be aware of the signs and symptoms of cirrhosis-related complications, particularly portal hypertension, and refer patients to specialists for further evaluation when warranted. Patients at risk for cirrhosis should be screened and the underlying etiologic factor(s) of the liver disease treated or appropriately managed when possible. Primary care physicians should be aware of the signs and symptoms of cirrhosis and its related complications and adopt a low threshold for referral to a specialist when the condition is suspected. An integrated, multidisciplinary approach to care between specialists and primary care physicians may improve early detection of cirrhosis and its related complications and strengthen management strategies.


The Effects of Traditional Chinese Medicine as an Auxiliary Treatment for COVID-19: A Systematic Review and Meta-Analysis.
Background: Coronavirus disease 2019 (COVID-19) has become a pandemic with no specific and widely accepted effective drug or vaccine. However, studies have shown that Traditional Chinese Medicine (TCM) may play a significant role as an auxiliary treatment for COVID-19. Objective: This study aimed to assess the effects of TCM as an auxiliary treatment for COVID-19 through a systematic review of randomized-controlled trials (RCTs). Methods: Four English and three Chinese language databases were searched from December 1, 2019, to June 30, 2020. RCTs comparing TCM in combination with Western medicine (WM) with the same WM therapies alone for confirmed COVID-19 patients were included. The outcome measures were cure rate, lowering of body temperature, cough relief, improvement in chest computed tomography (CT) images, deterioration of condition, and adverse effects. Methodological quality was assessed using the Cochrane risk-of-bias tool. A series of meta-analyses were conducted for selected outcomes using RevMan 5.3 software. The quality of evidence was appraised using the grading of recommendation, assessment, development, and evaluation (GRADE) recommendations. Results: Ten RCTs with a total of 1,285 patients were included. Compared with WM alone in treating COVID-19, WM with auxiliary treatment by TCM appears to have increased the cure rate (risk ratio [RR] 1.15 [95% confidence interval (CI) 1.04-1.26]), relieved cough (RR 1.32 [95% CI 1.15-1.52]), improved chest CT images (RR 1.23 [95% CI 1.11-1.37]), and reduced the number of cases transitioning from a moderate to severe condition (RR 0.58 [95% CI 0.43-0.77]). The authors are uncertain whether TCM combined WM has effects on fever normalization (RR 1.10 [95% CI 0.94-1.29]) or adverse effects (RR 0.81 (95% CI 0.42-1.57]). Although they evaluated the certainty of evidence for lowering body temperature and adverse effects as very low, and low for cure rate, certainty was evaluated as moderate for improvement in chest CT images, cough relief, and deterioration of condition. Conclusion: TCM may be an effective auxiliary treatment for COVID-19 patients, which is likely to help improve the main symptoms and reduce disease progression. However, due to the limited number of studies and apparent heterogeneity among them, a more definitive conclusion on the effect of TCM on lowering body temperature and adverse effects cannot be drawn at this time.


Short-Term Material Characterization by Electrohydraulic Incremental Extrusion through Micro Channels.
Conventional testing procedures for characterizing the mechanical behavior of materials require intense preparation in geometry and in the handling of the samples to apply specific stress conditions. Furthermore, these procedures are time consuming. In a novel method for high-throughput development of new material, spherical and cylindrical micro samples should also be tested within a short time. For mechanical testing, the samples need to be exposed to specific types of stress. As most conventional testing procedures are not applicable, new testing procedures are demanded. The incremental electrohydraulic extrusion of micro samples through micro channels is a new testing procedure that was introduced for short-term material characterization. Loading energy is used to cause shock waves that incrementally push the samples through the forming die. The resulting deformation progress is measured between the forming steps. In this research, process simulations are used for channel design and material flow analysis. The designed channels that cause specific stress in samples are realized by stacking elements radially or axially. The stacking enables sample access for measurement and unloading and ensures good machinability of the forming channels. New testing cases for short-term characterization of cylindrical as well as spherical micro samples by electrohydraulic extrusion are presented according to monotone tensile, compression, and torsion testing. Furthermore, production-related testing and cyclic load testing are introduced by incremental electrohydraulic extrusion. By measuring the deformation due to the dependence on supplied energy, flow curve equivalents are determined that correspond to values from conventional material testing procedures.


An Apple a Day: Which Bacteria Do We Eat With Organic and Conventional Apples?
Apples are among the most consumed fruits world-wide. They represent a source of direct human exposure to bacterial communities, which is less studied. We analyzed the apple microbiome to detect differences between tissues and the impact of organic and conventional management by a combined approach of 16S rRNA gene amplicon analysis and qPCR, and visualization using fluorescence in situ hybridization and confocal laser scanning microscopy (FISH-CLSM). Each apple fruit harbors different tissues (stem, peel, fruit pulp, seeds, and calyx), which were colonized by distinct bacterial communities. Interestingly, fruit pulp and seeds were bacterial hot spots, while the peel was less colonized. In all, approximately 108 16S rRNA bacterial gene copy numbers were determined in each g apple. Abundances were not influenced by the management practice but we found a strong reduction in bacterial diversity and evenness in conventionally managed apples. In addition, despite the similar structure in general dominated by Proteobacteria (80%), Bacteroidetes (9%), Actinobacteria (5%), and Firmicutes (3%), significant shifts of almost 40% of bacterial genera and orders were monitored. Among them, especially bacterial signatures known for health-affecting potential were found to be enhanced in conventionally managed apples. Our results suggest that we consume about 100 million bacterial cells with one apple. Although this amount was the same, the bacterial composition was significantly different in conventionally and organically produced apples.


Food offerings in Marshfield area businesses: a survey conducted in collaboration with the healthy lifestyles--Marshfield Area Coalition.
To survey Marshfield area businesses to determine the types of foods currently available to employees at the workplace and the potential need for nutrition information to facilitate the ordering of healthy food options at workplaces. A 2-page self-administered questionnaire was mailed to all businesses registered with the Marshfield Area of Chamber of Commerce. Questionnaires were mailed a second time to non-responders to improve the response rate. The questionnaire included items about foods available to employees at the workplace, cooking and eating facilities available to employees, and reasons for food choices made. Data were entered into an Excel spreadsheet, verified against the hard copies and transferred to SPSS for analysis. Completed questionnaires were returned by 249 businesses (41.1% participation). The reported number of minutes that most employees take for their lunch ranged from 0 to 60 (median = 30). Eighty-one percent of businesses (n = 184) reported that most employees take 30 or more minutes for their lunch. Respondents were asked to list the most common menu items purchased for consumption on-site. One hundred fifteen respondents listed sandwiches (46.2%), 101 listed pizza (40.6%), 30 listed salad (12.0%), and 17 listed various sweets (6.8%). Employees were thought to be less likely than managers to select foods lower in calories if the foods are more expensive. There is great potential to improve the health of employees through the provision of nutrition information to businesses. The survey employed in the current study can be used again in the future to track changes after implementation of worksite initiatives through the Business and Industry Committee of the Healthy Lifestyles--Marshfield Area Coalition.


Comparison of non-myeloablative lymphodepleting preconditioning regimens in patients undergoing adoptive T cell therapy.
Adoptive cell therapy with T cells genetically engineered to express a chimeric antigen receptor (CAR-T) or tumor-infiltrating T lymphocytes (TIL) demonstrates impressive clinical results in patients with cancer. Lymphodepleting preconditioning prior to cell infusion is an integral part of all adoptive T cell therapies. However, to date, there is no standardization and no data comparing different non-myeloablative (NMA) regimens. In this study, we compared NMA therapies with different doses of cyclophosphamide or total body irradiation (TBI) in combination with fludarabine and evaluated bone marrow suppression and recovery, cytokine serum levels, clinical response and adverse events. We demonstrate that a cumulative dose of 120 mg/kg cyclophosphamide and 125 mg/m2 fludarabine (120Cy/125Flu) and 60Cy/125Flu preconditioning were equally efficient in achieving deep lymphopenia and neutropenia in patients with metastatic melanoma, whereas absolute lymphocyte counts (ALCs) and absolute neutrophil counts were significantly higher following 200 cGyTBI/75Flu-induced NMA. Thrombocytopenia was most profound in 120Cy/125Flu patients. 30Cy/75Flu-induced preconditioning in patients with acute lymphoblastic leukemia resulted in a minor ALC decrease, had no impact on platelet counts and did not yield deep neutropenia. Following cell infusion, 120Cy/125Flu patients with objective tumor response had significantly higher ALC and significant lower inflammatory indexes, such as neutrophil-to-lymphocyte ratio (NLR) and platelet-to-lymphocyte ratio (PLR). Receiver-operating characteristics curve analysis 7 days after cell infusion was performed to determine the cut-offs, which distinguish between responding and non-responding patients in the 120Cy/125Flu cohort. NLR≤1.79 and PLR≤32.7 were associated with clinical response and overall survival. Cytokine serum levels did not associate with clinical response in patients with TIL. Patients in the 120Cy/125Flu cohort developed significantly more acute NMA-related adverse events, including thrombocytopenia, febrile neutropenia and cardiotoxicity, and stayed significantly longer in hospital compared with the 60Cy/125Flu and TBI/75Flu cohorts. Bone marrow depletion and recovery were equally affected by 120Cy/125Flu and 60Cy/125Flu preconditioning; however, toxicity and consequently duration of hospitalization were significantly lower in the 60Cy/125Flu cohort. Patients in the 30Cy/75Flu and TBI/75Flu groups rarely developed NMA-induced adverse events; however, both regimens were not efficient in achieving deep bone marrow suppression. Among the regimens, 60Cy/125Flu preconditioning seems to achieve maximum effect with minimum toxicity.


The human blood pressure chronome: a biological gauge of aging.
This study examines changes in the broad time structure (chronome) of blood pressure (BP) as a function of age. This is an observational study. The study was conducted at the Chronobiology Laboratories of the University oi Minnesota, Minneapolis, Minnesota. Seventy-two individuals 12 to 106 years of age provided a 7-day record of BP measured indirectly with an ambulatory monitor, mostly at 15-60-minute intervals. Amplitudes in least squares spectra at frequencies of 1 to 7 cycles per week and 1 to 8 cycles per day were analyzed by linear regression as a function of age. A two-way analysis of variance for subjects classified in four age groups tested for any variance transposition from the circadian (about-daily) to the infradian (frequency lower than one cycle per day) and/or to the ultradian (frequency higher than one cycle per day) domain. The decreasing circadian BP amplitude with age is accompanied by an increase in infradian and ultradian prominence. The day-to-day variability in circadian characteristics also increases with age. A variance transposition from the circadian to the neighboring ultradian and infradian domains characterizes the elderly human BP chronome, as a new, technically implementable biological, rather than chronological, gauge of human aging.


The duration of a brief event in the mind's eye.
A new illusion of perceived duration associated with focused spatial attention is reported. Brief flashes in attended locations were perceived to last longer than the same flashes in unattended locations. That illusion was shown to be completely independent of another illusion concerning the perceived onset of a flash, ruling out the possibility that the effect on perceived duration is derivative of a comparison between perceived onset and offset. The illusion also occurred when the event duration was composed of a temporal gap rather than a brief flash, ruling out low-level visible persistence as a basis for the illusion. Taken together, the results point to cortical connections from higher brain centers' both speeding and prolonging the visual signals occurring in lower sensory regions. Those temporal consequences could easily subserve many of the perceptual benefits ascribed to attention for spatial and intensive properties.


Using nonlinear transient growth to construct the minimal seed for shear flow turbulence.
Linear transient growth analysis is commonly used to suggest the structure of disturbances which are particularly efficient in triggering transition to turbulence in shear flows. We demonstrate that the addition of nonlinearity to the analysis can substantially change the prediction made in pipe flow from simple two-dimensional streamwise rolls to a spanwise and cross-stream localized three-dimensional state. This new nonlinear optimal is demonstrably more efficient in triggering turbulence than the linear optimal indicating that there are better ways to design perturbations to achieve transition.