Nail or plate fixation of intertrochanteric hip fractures: changing pattern of practice. A review of the American Board of Orthopaedic Surgery Database.
A new method of fixation for intertrochanteric hip fractures that involves the use of an intramedullary nail that interlocks proximally into the femoral head was introduced in the early 1990s. Anecdotal observation of practice patterns during the Part II (oral) American Board of Orthopaedic Surgery examination suggested that the use of this method had increased substantially in recent years in comparison with the more traditional sliding compression screw technique. A study of the Part II database was undertaken to detect changing patterns of care for intertrochanteric fractures. During the process of Board certification, candidates for the Part II (oral) examination submit a six-month surgical case list and patient data into a secure database. The database was searched for all intertrochanteric fractures (International Classification of Diseases, Ninth Revision, code 820.20 or 820.21) over a seven-year period (1999 through 2006). The cases were categorized by intramedullary nail or plate fixation on the basis of surgeon-reported Current Procedural Terminology codes. Relative utilization of the two devices was analyzed according to year and region, and the devices were compared in terms of complications and outcomes. A dramatic change in practice was demonstrated, with the intramedullary nail fixation rate increasing from 3% in 1999 to 67% in 2006. Regional variation was substantial. The highest rate of utilization of intramedullary nail fixation was recorded by candidates from the South, Southeast, and Southwest, who converted to the new technology faster than those in the Northeast, Northwest, and Midwest. Overall, patients managed with plate fixation had slightly less pain and deformity in comparison with those managed with intramedullary nailing, with no significant differences being identified in terms of function or satisfaction. Patients managed with intramedullary nailing had more procedure-related complications, particularly bone fracture. From 1999 to 2006, a dramatic change in surgeon preference for the fixation device used for the treatment of intertrochanteric fractures has occurred among young orthopaedic surgeons. This change has occurred despite a lack of evidence in the literature supporting the change and in the face of the potential for more complications.


A multicenter investigation with interphase fluorescence in situ hybridization using X- and Y-chromosome probes.
Twenty-six laboratories used X and Y chromosome probes and the same procedures to process and examine 15,600 metaphases and 49,400 interphases from Phaseolus vulgaris-leucoagglutinin (PHA)-stimulated lymphocytes. In Part I, each laboratory scored 50 metaphases and 200 interphases from a normal male and a normal female from its own practice. In Part II, each laboratory scored 50 metaphases and 200 interphases on slides prepared by a central laboratory from a normal male and a normal female and three mixtures of cells from the male and female. In Part III, each laboratory scored 50 metaphases (in samples of 5, 10, 15, and 20) and 100 interphases (in samples of 5, 10, 15, 20, and 50) on new, coded slides of the same specimens used in Part II. Metaphases from male specimens were scored as 98-99% XY with no XX cells, and 97-98% of interphases were scored as XY with 0.04% XX cells. Metaphases from female specimens were scored as 96-97% XX with 0.03% XY cells, and 94-96% of interphases were scored as XX with 0.05% XY cells. Considering the data as a model for any probe used with fluorescence in situ hybridization (FISH), a statistical approach assessing the impact of analytical sensitivity on the numbers of observations required to assay for potential mosaicisms and chimerisms is discussed. The workload associated with processing slides and scoring 50 metaphases and 200 interphases using FISH averaged 27.1 and 28.6 minutes, respectively. This study indicates that multiple laboratories can test/develop guidelines for the rapid, efficacious, and cost-effective integration of FISH into clinical service.


Baseline Plasma Aldosterone Level and Renin Activity Allowing Omission of Confirmatory Testing in Primary Aldosteronism.
Previous studies have proposed cutoff value of baseline plasma aldosterone concentration (bPAC) under renin suppression that could diagnose primary aldosteronism (PA) without confirmatory testing. However, those studies are limited by selection bias due to a small number of patients and a single-center study design. This study aimed to determine cutoff value of bPAC and baseline plasma renin activity (bPRA) for predicting positive results in confirmatory tests for PA. The multi-institutional, retrospective, cohort study was conducted using the PA registry in Japan (JPAS/JRAS). We compared bPAC in patients with PA who showed positive and negative captopril challenge test (CCT) or saline infusion test (SIT) results. Patients with PA who underwent CCT (n = 2256) and/or SIT (n = 1184) were studied. The main outcomes were cutoff value of bPAC (ng/dL) and bPRA (ng/mL/h) for predicting positive CCT and/or SIT results. In patients with renin suppression (bPRA ≤ 0.3), the cutoff value of bPAC that would give 100% specificity for predicting a positive SIT result was lower than that for predicting a positive CCT result (30.85 vs 56.35, respectively). Specificities of bPAC cutoff values ≥ 30.85 for predicting positive SIT and CCT results remained high (100.0% and 97.0%, respectively) in patients with bPRA ≤ 0.6. However, the specificities of bPAC cutoff values ≥ 30.85 for predicting positive SIT and CCT results decreased when patients with bPRA > 0.6 were included. Confirmatory testing could be omitted in patients with bPAC ≥ 30.85 in the presence of bPRA ≤ 0.6.


Comparison of home health and hospice care agencies by organizational characteristics and services provided: United States, 2007.
This report presents national estimates of the organizational characteristics of home health and hospice care agencies in 2007. Comparisons of organizational characteristics and provision of selected services are made by agency type. A comparison of selected characteristics between 1996 and 2007 is also provided to highlight changes that have occurred leading to the current composition of the home health and hospice care sector. Estimates are based on data collected on agencies from the 1996, 2000, and 2007 National Home and Hospice Care Survey, conducted by the Centers for Disease Control and Prevention's National Center for Health Statistics. Estimates are derived from data collected during interviews with administrators and staff designated by the administrators. In 2007, there were 14,500 home health and hospice care agencies in the United States, an increase from 11,400 in 2000. Three-quarters of these agencies provided home health care only, 15% provided hospice care only, and 10% provided both home health and hospice care (mixed). The percentage of proprietary home health care only and hospice care only agencies increased during 1996-2007, whereas the percentage of proprietary mixed agencies remained relatively stable. The average number of home health care patients that home health care only and mixed agencies served decreased, while the average number of hospice care patients that hospice care only agencies served increased across years. Among mixed agencies, no significant changes were observed in the average number of hospice care patients being served. The percentage of home health care only agencies offering certain therapeutic and nonmedical services declined over the years. There was an increase in the proportion of hospice care only agencies' providing many core and noncore hospice care services during 1996-2007. Also during this time, the proportion of mixed agencies providing selected nonmedical services decreased.


Gender differences in the relationship of homelessness to symptom severity, substance abuse, and neuroleptic noncompliance in schizophrenia.
This study examined gender differences in the relationship of homelessness in schizophrenia to symptom severity, risk behaviors, and prognostic features. Four hundred subjects with schizophrenia were studied: 100 homeless men, 100 homeless women, 100 never homeless men, and 100 never homeless women. Assessments included derivation of five symptom factors by using the Positive and Negative Syndrome Scale (PANSS). Homelessness for the entire sample was associated with greater severity of positive, activation, and autistic preoccupation symptoms, younger age at first hospitalization, and substance abuse (SA). For men only, homelessness was associated with neuroleptic noncompliance (NN). When NN and SA were statistically controlled, symptom severity was not different between the homeless and never homeless. Women, independent of residential status, had more severe negative, activation, and autistic preoccupation symptoms that were not associated with prognostic features or risk behaviors. For both men and women, SA was associated with homelessness, but independent of residence, SA was less severe in women. Additionally, SA was less severe in homeless women than never homeless men. Thus, symptom severity in homeless individuals with schizophrenia appears as an interaction of symptom profiles and risk behaviors that are gender specific. Although cross-sectional analyses cannot distinguish cause from effect, these findings suggest gender-specific routes to homelessness among indigent urban adults with schizophrenia.


Optimization of Taylor spatial frame half-pins diameter for bone deformity correction: Application to femur.
Using external fixtures for bone deformity correction takes advantages of less soft tissue injury, better bone alignment and enhances strain development for bone formation on cutting section, which cause shorter healing time. Among these fixtures, Taylor spatial frame is widely used and includes two rings and six adjustable struts developing 6 degrees of freedom, making them very flexible for this type of application. The current study describes a method to optimize Taylor spatial frame pin-sizes currently chosen from the surgeon's experiences. A three-dimensional model of femur was created from computed tomography images; segmentation of the medical images was made based on the Hounsfield unit (gray scale) in order to allocate adequate mechanical properties into cortical and trabecular bone sections. Both the cortical and trabecular sections were assumed to be isotropic and homogeneous. The diameter optimization of Taylor spatial frame's half-pins was carried out by coupling genetic algorithm and finite element analysis. The finite element analysis was based on a static mechanical load corresponding to a standing person's body weight. Finite element analysis results were validated with experimentally measured strains obtained from bone compression tests. A cost function, based on the developed bone stresses, was defined close to the Taylor spatial frame's half-pins. The calculated cost function showed a decrease of over 33% from the initial half-pin selection by the surgeon and the genetic algorithm optimization. Consequently, the maximum stresses experienced by the bone in the connected location of the half-pins decreased from 121.4 MPa in the surgeon's selection to 73.07 MPa as a result of the optimization process.


The Flavone Luteolin, an Endocrine Disruptor, Relaxed Male Guinea Pig Gallbladder Strips.
Luteolin (3',4',5,7-tetrahydroxyflavone) is a flavone with a yellow crystalline appearance present in numerous plants such as broccoli, green chili, and carrot. Luteolin is considered to be an endocrine disruptor with potent estrogen agonist activity and potent progesterone antagonist activity. Luteolin has effects on smooth muscle. Luteolin relaxed guinea pig trachea smooth muscle as it inhibited both phosphodiesterase and reduced intracellular Ca2+. Luteolin also caused vasorelaxation in rat thoracic aorta smooth muscle by inhibiting intracellular Ca2+ release, inhibition of sarcolemmal Ca2+ channels, and activation of K+ channels. Luteolin or its glycosides from artichoke extracts may have an ameliorating effect on irritable bowel syndrome. The purpose of this study was to determine if luteolin had an effect on gallbladder motility. An in vitro pharmacologic technique was utilized. Either cholecystokinin octapeptide (CCK) or KCl were used to induce tension in male guinea pig gallbladder strips maintained in Sawyer-Bartlestone chambers. Luteolin relaxed either the CCK- or KCl-induced tension in a concentration dependent manner. Various blockers were added to the chambers to determine which second messenger system(s) mediated the observed relaxation. Paired t-tests were used for statistical analysis. Differences between mean values of P < 0.05 were considered significant. Treatment of the gallbladder strips with luteolin prior to either KCl or CCK significantly (P < 0.001) decreased the amount of either KCl- or cholecystokinin-induced tension. The 2-aminoethoxydiphenylborane was used to ascertain if the release of intracellular Ca2+ mediated the luteolin-induced relaxation. It significantly (P < 0.001) decreased the amount of luteolin-induced relaxation. To ascertain if PKA mediated the luteolin-induced relaxation, PKA inhibitor 14-22 amide myristolated was used. It significantly (P < 0.01) reduced the amount of luteolin-induced relaxation. Neither KT5823, NG-methyl-L-arginine acetate salt, genistein, tetraethylammonium, nor fulvestrant had a significant effect. To ascertain if PKC mediated the luteolin-induced relaxation, the PKC inhibitors bisindolymaleimide IV and chelerythrine Cl- were used together. They had no significant effect. Luteolin relaxed cholecystokinin- or KCl-induced tension by blocking extracellular Ca2+ entry as well as intracellular Ca2+ release. In addition, the actions of PKA are also involved in mediating the luteolin effect.


Association of long-term administration of the survivin mRNA-targeted antisense oligonucleotide LY2181308 with reversible kidney injury in a patient with metastatic melanoma.
A 57-year-old man with metastatic melanoma was treated with the survivin inhibitor and antisense oligonucleotide LY2181308 as part of a First-in-Human Dose trial. After 18 months of treatment, he developed kidney injury and the treatment was discontinued. At 9 months and before the development of kidney injury, LY2181308 concentrations were 8- to 10-fold higher relative to median predicted values, but within the targeted exposure considered to be safe. However, at 17 months, 28 days after stopping LY2181308 therapy, LY2181308 concentration exceeded the predicted range by 38-fold. His decreased kidney function was slow to improve after stopping treatment. A kidney biopsy showed signs of acute tubular injury with regeneration. Complete recovery of kidney function occurred 6 months after treatment was stopped. The relationship between high exposures and slow LY2181308 clearance with the gradual improvement in kidney function after stopping the antisense treatment suggests that the oligonucleotide was related to the kidney injury. Based on this case report, kidney function should be monitored frequently in patients receiving long-term treatment with antisense oligonucleotides that specifically target survivin, particularly when they receive concomitant angiotensin-converting enzyme inhibitors or nonsteroidal anti-inflammatory drugs.


Genomic and transcriptomic analysis reveal molecular basis of salinity tolerance in a novel strong salt-tolerant rice landrace Changmaogu.
Salt stress is an important factor that limits rice yield. We identified a novel, strongly salt tolerant rice landrace called Changmaogu (CMG) collected from a coastal beach of Zhanjiang, Guangdong Province, China. The salt tolerance of CMG was much better than that of the international recognized salt tolerant rice cultivar Pokkali in the germination and seedling stages. To understand the molecular basis of salt tolerance in CMG, we performed BSA-seq for two extreme bulks derived from the cross between CMG and a cultivar sensitive to salt, Zhefu802. Transcriptomic sequencing was conducted for CMG at the germination and young seedling stages. Six candidate regions for salt tolerance were mapped on Chromosome 1 by BSA-seq using the extreme populations. Based on the polymorphisms identified between both parents, we detected 32 genes containing nonsynonymous coding single nucleotide polymorphisms (SNPs) and frameshift mutations in the open reading frame (ORF) regions. With transcriptomic sequencing, we detected a large number of differentially expressed genes (DEGs) at the germination and seedling stages under salt stress. KEGG analysis indicated two of 69 DEGs shared at the germination and seedling stages were significantly enriched in the pathway of carotenoid biosynthesis. Of the 169 overlapping DEGs among three sample points at the seedling stage, 13 and six DEGs were clustered into the pathways of ABA signal transduction and carotenoid biosynthesis, respectively. Of the 32 genes carrying sequence variation, only OsPP2C8 (Os01g0656200) was differentially expressed in the young seedling stage under salt stress and also showed sequence polymorphism in the ORFs between CMG and Zhefu802. OsPP2C8 was identified as the target candidate gene for salinity tolerance in the seedling stage. This provides an important genetic resource for the breeding of novel salt tolerant rice cultivars.


Efficacy of and resistance to anti-IGF-1R therapies in Ewing's sarcoma is dependent on insulin receptor signaling.
Identification of patient selection criteria and understanding of the potential mechanisms involved in the development of resistance are crucial for an appropriate and successful design of clinical trials with anti-insulin-like growth factor (IGF)-1R therapies. Few Ewing's sarcomas are highly sensitive to IGF-1R targeting and understanding the reason why, may hold the secret to improve successful treatments. In this paper, we show that a major mechanism of resistance to highly specific inhibitors of IGF-1R, either antibodies or tyrosine kinase inhibitors may involve enhanced insulin receptor (IR)-A homodimer formation and IGF-2 production. Resistant cells are able to switch from IGF-1/IGF-1R to IGF-2/IR-A dependency to maintain sustained activation of AKT and ERK1/2, proliferation, migration and metastasis. These cells also showed higher proliferative response to insulin, in keeping with a switch towards insulin pathways sustaining proliferation and malignancy, rather than metabolism. Our findings demonstrate a role for IR-A in eliciting intrinsic and adaptive resistance to anti-IGF-1R therapies. Thus, we indicate that tumors with low IGF-1R:IR ratio are unlikely to greatly benefit from anti-IGF-1R therapies and that the efficacy of anti-IGF-1R therapies should be evaluated in relationship to the IR-A:IGF-1R ratio in cancer cells. Moreover, we provide evidences supporting IR-A as an important target in sarcoma therapy.


Family- and genus-level 16S rRNA-targeted oligonucleotide probes for ecological studies of methanotrophic bacteria.
Methanotrophic bacteria play a major role in the global carbon cycle, degrade xenobiotic pollutants, and have the potential for a variety of biotechnological applications. To facilitate ecological studies of these important organisms, we developed a suite of oligonucleotide probes for quantitative analysis of methanotroph-specific 16S rRNA from environmental samples. Two probes target methanotrophs in the family Methylocystaceae (type II methanotrophs) as a group. No oligonucleotide signatures that distinguish between the two genera in this family, Methylocystis and Methylosinus, were identified. Two other probes target, as a single group, a majority of the known methanotrophs belonging to the family Methylococcaceae (type I/X methanotrophs). The remaining probes target members of individual genera of the Methylococcaceae, including Methylobacter, Methylomonas, Methylomicrobium, Methylococcus, and Methylocaldum. One of the family-level probes also covers all methanotrophic endosymbionts of marine mollusks for which 16S rRNA sequences have been published. The two known species of the newly described genus Methylosarcina gen. nov. are covered by a probe that otherwise targets only members of the closely related genus Methylomicrobium. None of the probes covers strains of the newly proposed genera Methylocella and "Methylothermus," which are polyphyletic with respect to the recognized methanotrophic families. Empirically determined midpoint dissociation temperatures were 49 to 57 degrees C for all probes. In dot blot screening against RNA from positive- and negative-control strains, the probes were specific to their intended targets. The broad coverage and high degree of specificity of this new suite of probes will provide more detailed, quantitative information about the community structure of methanotrophs in environmental samples than was previously available.


PICK1 expression in the Drosophila central nervous system primarily occurs in the neuroendocrine system.
The protein interacting with C kinase 1 (PICK1) protein was first identified as a novel binding partner for protein kinase C. PICK1 contains a membrane-binding BAR domain and a PDZ domain interacting with many synaptic proteins, including the alpha-amino-3-hydroxy-5-methylisoxazole-4-propionic acid (AMPA) receptor subunit GluR2 and the dopamine transporter. PICK1 is strongly implicated in GluR2 trafficking and synaptic plasticity. In mammals, PICK1 has been characterized extensively in cell culture studies. To study PICK1 in an intact system, we characterized PICK1 expression immunohistochemically in the adult and larval Drosophila central nervous system. PICK1 was found in cell bodies in the subesophageal ganglion, the antennal lobe, the protocerebrum, and the neuroendocrine center pars intercerebralis. The cell types that express PICK1 were identified using GAL4 enhancer trap lines. The PICK1-expressing cells form a subpopulation of neurons. PICK1 immunoreactivity was neither detected in glutamatergic nor in dopaminergic neurons. Also, we observed PICK1 expression in only a few GABAergic neurons, located in the antennal lobe. In contrast, we detected robust PICK1 immunolabeling of peptidergic neurons in the neuroendocrine system, which express the transcription factor DIMM and the amidating enzyme peptidylglycine-alpha-hydroxylating monooxygenase (PHM). The PICK1-positive cells include neurosecretory cells that produce the insulin-like peptide dILP2. PICK1 expression in insulin-producing cells also occurs in mammals, as it was also observed in a rat insulinoma cell line derived from pancreatic beta-cells. At the subcellular level, PICK1 was found in the perinuclear zone but surprisingly not in synaptic domains. We conclude that PICK1 may serve an important role in the neuroendocrine system both in insects and vertebrates.


Interaction of PPARG Pro12Ala with dietary fat influences plasma lipids in subjects at cardiometabolic risk.
The PPARγ2 gene single nucleotide polymorphism (SNP) Pro12Ala has shown variable association with metabolic syndrome traits in healthy subjects. The RISCK Study investigated the effect of interaction between genotype and the ratio of polyunsaturated:saturated (P:S) fatty acid intake on plasma lipids in 367 white subjects (ages 30-70 years) at increased cardiometabolic risk. Interaction was determined after habitual diet at recruitment, at baseline after a 4-week high-SFA (HS) diet, and after a 24-week reference (HS), high-MUFA (HM), or low-fat (LF) diet. At recruitment, there were no significant associations between genotype and plasma lipids; however, P:S × genotype interaction influenced plasma total cholesterol (TC) (P = 0.02), LDL-cholesterol (LDL-C) (P = 0.002), and triglyceride (TG) (P = 0.02) concentrations. At P:S ratio ≤ 0.33, mean TC and LDL-C concentrations in Ala12 allele carriers were significantly higher than in noncarriers (respectively, P = 0.003; P = 0.0001). Significant trends in reduction of plasma TC (P = 0.02) and TG (P = 0.002) concentrations occurred with increasing P:S (respectively, ≤0.33 to >0.65; 0.34 to >0.65) in Ala12 allele carriers. There were no significant differences between carriers and noncarriers after the 4-week HS diet or 24-week interventions. Plasma TC and TG concentrations in PPARG Ala12 allele carriers decrease as P:S increases, but they are not dependent on a reduction in SFA intake.


Antimicrobial activity of stingless bee (Trigona sp.) propolis used in the folk medicine of Western Maharashtra, India.
Stingless bee (Trigona sp.) propolis is widely used in the folk medicine of Western Maharashtra, India to treat a variety of ailments. To determine the chemical composition and evaluate the antimicrobial activity of Indian stingless bee propolis. Chemical composition of the ethanolic extract of propolis (EEP) was determined by GC-MS analysis. A range of bacteria including multidrug resistant (MDR) cultures as well as a yeast strain was tested for antimicrobial activity using EEP. MIC, MBC, MFC, Kill curves and post agent effect (PAE) of the EEP were assessed using standard microbiological methods. GC-MS analysis revealed that propolis contained 24 compounds (9 known and 15 newly reported). Many of these were known bioactive compounds, including antimicrobials. The MICs of EEP were in the range of 1.21-9.75μg/mL while the MBCs/MFC were between 2.43 and 19.5μg/mL. The time required to achieve 90% (1 log(10)) reduction in culture growth ranged between 1.06 and 3.53h at their respective MIC values. PAE for all the cultures was >24h. Indian stingless bee propolis has a complex nature with 24 chemical compounds. It has a potent broad-spectrum antimicrobial activity. The latter finding, in conjunction with other bioactive properties, could provide a scientific basis to its popular use in the Indian folk medicine.


Estimated time of arrival and debiasing the time saving bias.
The time saving bias predicts that the time saved when increasing speed from a high speed is overestimated, and underestimated when increasing speed from a slow speed. In a questionnaire, time saving judgements were investigated when information of estimated time to arrival was provided. In an active driving task, an alternative meter indicating the inverted speed was used to debias judgements. The simulated task was to first drive a distance at a given speed, and then drive the same distance again at the speed the driver judged was required to gain exactly 3 min in travel time compared with the first drive. A control group performed the same task with a speedometer and saved less than the targeted 3 min when increasing speed from a high speed, and more than 3 min when increasing from a low speed. Participants in the alternative meter condition were closer to the target. The two studies corroborate a time saving bias and show that biased intuitive judgements can be debiased by displaying the inverted speed. Practitioner Summary: Previous studies have shown a cognitive bias in judgements of the time saved by increasing speed. This simulator study aims to improve driver judgements by introducing a speedometer indicating the inverted speed in active driving. The results show that the bias can be reduced by presenting the inverted speed and this finding can be used when designing in-car information systems.


Methodology for the Study of Horizontal Gene Transfer in Staphylococcus aureus.
One important feature of the major opportunistic human pathogen Staphylococcus aureus is its extraordinary ability to rapidly acquire resistance to antibiotics. Genomic studies reveal that S. aureus carries many virulence and resistance genes located in mobile genetic elements, suggesting that horizontal gene transfer (HGT) plays a critical role in S. aureus evolution. However, a full and detailed description of the methodology used to study HGT in S. aureus is still lacking, especially regarding natural transformation, which has been recently reported in this bacterium. This work describes three protocols that are useful for the in vitro investigation of HGT in S. aureus: conjugation, phage transduction, and natural transformation. To this aim, the cfr gene (chloramphenicol/florfenicol resistance), which confers the Phenicols, Lincosamides, Oxazolidinones, Pleuromutilins, and Streptogramin A (PhLOPSA)-resistance phenotype, was used. Understanding the mechanisms through which S. aureus transfers genetic materials to other strains is essential to comprehending the rapid acquisition of resistance and helps to clarify the modes of dissemination reported in surveillance programs or to further predict the spreading mode in the future.


Air Pollution (Particulate Matter) Exposure and Associations with Depression, Anxiety, Bipolar, Psychosis and Suicide Risk: A Systematic Review and Meta-Analysis.
Particulate air pollution's physical health effects are well known, but associations between particulate matter (PM) exposure and mental illness have not yet been established. However, there is increasing interest in emerging evidence supporting a possible etiological link. This systematic review aims to provide a comprehensive overview and synthesis of the epidemiological literature to date by investigating quantitative associations between PM and multiple adverse mental health outcomes (depression, anxiety, bipolar disorder, psychosis, or suicide). We undertook a systematic review and meta-analysis. We searched Medline, PsycINFO, and EMBASE from January 1974 to September 2017 for English-language human observational studies reporting quantitative associations between exposure to PM <1.0μm in aerodynamic diameter (ultrafine particles) and PM <2.5 and <10μm in aerodynamic diameter (PM2.5 and PM10, respectively) and the above psychiatric outcomes. We extracted data, appraised study quality using a published quality assessment tool, summarized methodological approaches, and conducted meta-analyses where appropriate. Of 1,826 citations identified, 22 met our overall inclusion criteria, and we included 9 in our primary meta-analyses. In our meta-analysis of associations between long-term (>6 months) PM2.5 exposure and depression (n=5 studies), the pooled odds ratio was 1.102 per 10-μg/m3 PM2.5 increase (95% CI: 1.023, 1.189; I2=0.00%). Two of the included studies investigating associations between long-term PM2.5 exposure and anxiety also reported statistically significant positive associations, and we found a statistically significant association between short-term PM10 exposure and suicide in meta-analysis at a 0-2 d cumulative exposure lag. Our findings support the hypothesis of an association between long-term PM2.5 exposure and depression, as well as supporting hypotheses of possible associations between long-term PM2.5 exposure and anxiety and between short-term PM10 exposure and suicide. The limited literature and methodological challenges in this field, including heterogeneous outcome definitions, exposure assessment, and residual confounding, suggest further high-quality studies are warranted to investigate potentially causal associations between air pollution and poor mental health. https://doi.org/10.1289/EHP4595.


Diminished bone formation in experimental diabetes. Relationship to osteoid maturation and mineralization.
The pathogenesis of osteopenia in clinical diabetes remains uncertain. Thus, bone formation, mineralization, and resorption were measured over a 10-day period using double-tetracycline labeling of bone in control (C, N = 18), untreated diabetic (I-, N = 14), and insulin-treated diabetic (I+, N = 16) rats. Diabetes was induced by the intravenous (i.v.) injection of streptozotocin (STZ), 90 mg/kg, in citrate buffer. Bone and matrix (osteoid) formation and apposition were decreased by 50% from C values in I- rats (P less than 0.05), but were unchanged in I+ rats. Osteoid seam width and osteoid area were also less in I- (P less than 0.05), but similar in I+, when compared with C. In untreated diabetic rats that continued to actively form new bone, osteoid maturation and mineralization were not diminished when adjusted for the rate of bone formation. However, 5 of 14 untreated and 2 of 16 insulin-treated diabetic animals showed no uptake of tetracycline into bone (Chi-square, 8.54; P less than 0.05), suggesting a defect in mineralization in a subset of diabetic rats. Measurements of serum glucose, calcium, and phosphorus concentrations, of urinary excretion rates for glucose, calcium, and phosphorus, and of creatinine clearance failed to correlate with the changes in bone growth and histology observed. The results indicate heterogeneity in the response of bone in diabetes, and suggest that bone formation and osteoid volume are reduced early in the course of this disorder. These data in short-term diabetes support previous observations in both man and rat that indicate a state of low bone turnover in diabetes.


Anti-inflammatory properties of prostaglandin E2: deletion of microsomal prostaglandin E synthase-1 exacerbates non-immune inflammatory arthritis in mice.
Prostanoids and PGE2 in particular have been long viewed as one of the major mediators of inflammation in arthritis. However, experimental data indicate that PGE2 can serve both pro- and anti-inflammatory functions. We have previously shown (Kojima et al., J. Immunol. 180 (2008) 8361-8368) that microsomal prostaglandin E synthase-1 (mPGES-1) deletion, which regulates PGE2 production, resulted in the suppression of collagen-induced arthritis (CIA) in mice. This suppression was attributable, at least in part, to the impaired generation of type II collagen autoantibodies. In order to examine the function of mPGES-1 and PGE2 in a non-autoimmune form of arthritis, we used the collagen antibody-induced arthritis (CAIA) model in mice deficient in mPGES-1, thereby bypassing the engagement of the adaptive immune response in arthritis development. Here we report that mPGES-1 deletion significantly increased CAIA disease severity. The latter was associated with a significant (~3.6) upregulation of neutrophil, but not macrophage, recruitment to the inflamed joints. The lipidomic analysis of the arthritic mouse paws by quantitative liquid chromatography/tandem mass-spectrometry (LC/MS/MS) revealed a dramatic (~59-fold) reduction of PGE2 at the peak of arthritis. Altogether, this study highlights mPGES-1 and its product PGE2 as important negative regulators of neutrophil-mediated inflammation and suggests that specific mPGES-1 inhibitors may have differential effects on different types of inflammation. Furthermore, neutrophil-mediated diseases could be exacerbated by inhibition of mPGES-1.


Risk of adverse outcomes in patients with rheumatoid arthritis hospitalized for stroke-a cross-sectional study.
Specific data regarding the full range of stroke outcomes among patients with rheumatoid arthritis (RA) are lacking. This study aimed to investigate outcomes in RA patients hospitalized for a stroke. The study retrieved data from the Taiwan Longitudinal Health Insurance Database 2005. We identified 26,336 patients who were hospitalized for stroke treatment. Of these patients, 736 patients with a prior diagnosis of RA before the index hospitalization were selected as the study group. We selected 2208 age-sex-matched patients without RA as the comparison group. We performed conditional logistic regressions to calculate odds ratios (ORs) for in-hospital mortality and secondary diagnoses of pneumonia, urinary tract infections (UTIs), peptic ulcers, acute respiratory failure, and the use of mechanical ventilation to compare RA patients and comparison patients. We also compared the length of stay (LOS) and hospitalization costs between patients with RA and comparison patients. We found that RA patients had a significantly increased risk of peptic ulcer during the stroke hospitalization (OR = 1.52, 95% CI = 1.05-2.20). However, there were no significant differences between patients with RA and comparison patients in terms of in-hospital mortality, pneumonia, UTIs, acute respiratory failure, or the use of mechanical ventilation. Furthermore, the LOS of stroke hospitalization did not differ between the two groups. We concluded that RA patients hospitalized for a stroke do not have a significantly different risk of in-hospital mortality, pneumonia, UTIs, and mechanical ventilator use, but they have a higher risk of peptic ulcers. Additionally, among patients with a subarachnoid/intracerebral hemorrhagic stroke, RA patients were more likely to have received mechanical ventilation than comparison patients (adjusted OR = 1.89, 95% CI = 1.14-3.15).


Dysfunctional affect regulation in borderline personality disorder and in somatoform disorder.
Although affect dysregulation is considered a core component of borderline personality disorder (BPD) and somatoform disorders (SoD), remarkably little research has focused on the prevalence and nature of affect dysregulation in these disorders. Also, despite apparent similarities, little is known about how dysfunctional under- and overregulation of affect and positive and negative somatoform and psychoform dissociative experiences inter-relate. Prior studies suggest a clear relationship between early childhood psychological trauma and affect dysregulation, especially when the caretaker is emotionally, sexually, or physically abusing the child, but how these relate to under- and overregulation while differentiating for developmental epochs is not clear. Although an elevated risk of childhood trauma exposure or complex posttraumatic stress disorder (CPTSD) symptoms has been reported in BPD and SoD, trauma histories, dysfunctional affect regulation, dissociation, PTSD, and CPTSD were never assessed in unison in BPD and/or SoD. BPD and/or SoD diagnoses were confirmed or ruled out in 472 psychiatric inpatients using clinical interviews. Dysfunctional under- and overregulation of affect and somatoform and psychoform dissociation, childhood trauma-by-primary-caretaker (TPC), PTSD, and CPTSD were all measured using self reports. No disorder-specific form of dysfunctional affect regulation was found. Although both BPD and SoD can involve affect dysregulation and dissociation, there is a wide range of intensity of dysfunctional regulation phenomena in patients with these diagnoses. Evidence was found for the existence of three qualitatively different forms of experiencing states: inhibitory experiencing states (overregulation of affect and negative psychoform dissociation) most commonly found in SoD, excitatory experiencing states (underregulation of affect and positive psychoform dissociation) most commonly found in BPD, and combination of inhibitory and excitatory experiencing states commonly occurring in comorbid BPD+SoD. Almost two-thirds of participants reported having experienced childhood TPC. Underregulation of affect was associated with emotional TPC and TPC occurring in developmental epoch, 0-6 years of age. Overregulation of affect was associated with physical TPC. Almost a quarter of all participants met the criteria for CPTSD. BPD+SoD patients had the most extensive childhood trauma histories and were most likely to meet CPTSD criteria, followed by BPD, psychiatric comparison (PC), and SoD. The BPD+SoD and BPD reported significantly higher levels of CPTSD than the SoD or PC groups but did not differ from each other except for greater severity of CPTSD somatic symptoms by the BPD+SoD group. THREE QUALITATIVELY DIFFERENT FORMS OF DYSFUNCTIONAL REGULATION WERE IDENTIFIED: inhibitory, excitatory, and combined inhibitory and excitatory states. Distinguishing inhibitory versus excitatory states of experiencing may help to clarify differences in dissociation and affect dysregulation between and within BPD and SoD patients. Specific interventions addressing overregulation in BPD, or underregulation in SoD, should be added to disorder-specific evidence-based treatments. CPT is particularly prevalent in BPD and BPD+SoD and is differentially associated with under- and overregulation of affect depending on the type of traumatic exposure. CPTSD warrants further investigation as a potential independent syndrome or as a marker identifying a sub-group of affectively, or both affectively and somatically, dysregulated patients diagnosed with BPD who have childhood trauma histories.


Enhanced corticomotor excitability with dynamic fatiguing exercise of the lower limb in multiple sclerosis.
To determine if task performance and fatigability during rapid repetitive exercise of the lower limb differ in a group of MS subjects compared to a control group, and what central changes accompany the development of fatigue and the period of recovery. Transcranial magnetic stimulation (TMS) was used to compare motor evoked potential (MEP) responses between 10 clinically definite MS subjects (7F, 33-64 years of age; EDSS <or= 4; MRC grade >or= 4/5) and 13 control subjects during and after 5 bouts of a 15-second maximum rate foot-tapping task performed at 1 minute intervals. Maximum voluntary contraction (MVC) force of ankle dorsiflexion was lower (15 %) in the MS group compared to controls; however there were no differences in the rate of foot tapping. The rate of foot tapping decreased during each bout of exercise to a comparable degree in both groups, but there was no overall deterioration in performance across the 5 repeat bouts in either group. MS subjects showed a greater decline in strength than controls after exercise (20.7+/-7.7% vs. 6+/-3.6%; p<0.05). MEP amplitude increased significantly for the exercised limb in both groups, but the increase was greater in MS subjects (65.9+/-27% vs. 31+/-19.6%; MS vs. control; p<0.05). MEP amplitude also increased for the non-exercised limb in controls (40.6+/-15.6%, p<0.01) but not in MS subjects. Mild to moderately affected MS subjects can perform a fatiguing exercise requiring a high level of central motor control but this is associated with a greater strength loss and increase in corticomotor excitability compared to unaffected individuals. Central adaptive processes are likely to have a significant role in maintaining task performance in MS.


p21CDKN1A does not interfere with loading of PCNA at DNA replication sites, but inhibits subsequent binding of DNA polymerase delta at the G1/S phase transition.
The ability of the cyclin-dependent kinase (CDK) inhibitor p21CDKN1A to interact with PCNA recruited to DNA replication sites was investigated to elucidate the relevance of this interaction in cell cycle arrest. To this end, expression of p21 protein fused to green fluorescent protein (GFP) was induced in HeLa cells. G1 phase cell cycle arrest induced by p21GFP occurred also at the G1/S transition, as shown by cyclin A immunostaining of GFP-positive cells. Confocal microscopy analysis and co-immunoprecipitation studies showed that p21GFP co-localized and interacted with chromatin-bound PCNA and CDK2. GFP-p21 mutant forms unable to bind to PCNA (p21PCNA-) or CDK (p21CDK-) induced cell cycle arrest, although immunoprecipitation experiments showed these mutants to be unstable. Expression of HA-tagged p21wt or mutant proteins confirmed the ability of both mutants to arrest cell cycle. p21(wt)HA and p21CDK-HA, but not p21PCNA-, co-localized and co-immunoprecipitated with chromatin-bound PCNA. Association of p21 to chromatin-bound PCNA resulted in the loss of interaction with the p125 catalytic subunit of DNA polymerase delta (pol delta). These results suggest that in vivo p21 does not interfere with loading of PCNA at DNA replication sites, but prevents, or displaces subsequent binding of pol delta to PCNA at the G1/S phase transition.


Recent range expansion in Australian hummock grasses (Triodia) inferred using genotyping-by-sequencing.
The Australian arid zone (AAZ) has undergone aridification and the formation of vast sandy deserts since the mid-Miocene. Studies on AAZ organisms, particularly animals, have shown patterns of mesic ancestry, persistence in rocky refugia and range expansions in arid lineages. There has been limited molecular investigation of plants in the AAZ, particularly of taxa that arrived in Australia after the onset of aridification. Here we investigate populations of the widespread AAZ grass Triodia basedowii to determine whether there is evidence for a recent range expansion, and if so, its source and direction. We also undertake a dating analysis for the species complex to which T. basedowii belongs, in order to place its diversification in relation to changes in AAZ climate and landscapes. We analyse a genomic single nucleotide polymorphism data set from 17 populations of T. basedowii in a recently developed approach for detecting the signal and likely origin of a range expansion. We also use alignments from existing and newly sequenced plastomes from across Poaceae for analysis in BEAST to construct fossil-calibrated phylogenies. Across a range of sampling parameters and outgroups, we detected a consistent signal of westward expansion for T. basedowii, originating in central or eastern Australia. Divergence time estimation indicates that Triodia began to diversify in the late Miocene (crown 7.0-8.8 million years (Ma)), and the T. basedowii complex began to radiate during the Pleistocene (crown 1.4-2.0 Ma). This evidence for range expansion in an arid-adapted plant is consistent with similar patterns in AAZ animals and likely reflects a general response to the opening of new habitat during aridification. Radiation of the T. basedowii complex through the Pleistocene has been associated with preferences for different substrates, providing an explanation why only one lineage is widespread across sandy deserts.


Injectable hydrogels with high fixed charge density and swelling pressure for nucleus pulposus repair: biomimetic glycosaminoglycan analogues.
The load-bearing biomechanical role of the intervertebral disc is governed by the composition and organization of its major macromolecular components, collagen and aggrecan. The major function of aggrecan is to maintain tissue hydration, and hence disc height, under the high loads imposed by muscle activity and body weight. Key to this role is the high negative fixed charge of its glycosaminoglycan side chains, which impart a high osmotic pressure to the tissue, thus regulating and maintaining tissue hydration and hence disc height under load. In degenerate discs, aggrecan degrades and is lost from the disc, particularly centrally from the nucleus pulposus. This loss of fixed charge results in reduced hydration and loss of disc height; such changes are closely associated with low back pain. The present authors developed biomimetic glycosaminoglycan analogues based on sulphonate-containing polymers. These biomimetics are deliverable via injection into the disc where they polymerize in situ, forming a non-degradable, nuclear "implant" aimed at restoring disc height to degenerate discs, thereby relieving back pain. In vitro, these glycosaminoglycan analogues possess appropriate fixed charge density, hydration and osmotic responsiveness, thereby displaying the capacity to restore disc height and function. Preliminary biomechanical tests using a degenerate explant model showed that the implant adapts to the space into which it is injected and restores stiffness. These hydrogels mimic the role taken by glycosaminoglycans in vivo and, unlike other hydrogels, provide an intrinsic swelling pressure, which can maintain disc hydration and height under the high and variable compressive loads encountered in vivo.


Adaptive optics for structured illumination microscopy.
We implement wave front sensor-less adaptive optics in a structured illumination microscope. We investigate how the image formation process in this type of microscope is affected by aberrations. It is found that aberrations can be classified into two groups, those that affect imaging of the illumination pattern and those that have no influence on this pattern. We derive a set of aberration modes ideally suited to this application and use these modes as the basis for an efficient aberration correction scheme. Each mode is corrected independently through the sequential optimisation of an image quality metric. Aberration corrected imaging is demonstrated using fixed fluorescent specimens. Images are further improved using differential aberration imaging for reduction of background fluorescence.


Chronic kidney disease: Statins in chronic kidney disease: time to move on?
Statins reduce the risk of atherosclerotic vascular disease in healthy individuals and those with chronic kidney disease (CKD); however, clinical trials have suggested a minimal effect of statins on CKD progression. The PLANET trials compared the renal effects of rosuvastatin and atorvastatin, but the findings leave many questions unanswered.


Epidemiology of Vascular Dementia.
The notion of what qualifies as vascular dementia has varied greatly since the first mention of dementia after apoplexy in ancient literature. Current insight points towards a multifactorial cause of cognitive decline at old age, in which vascular components like atherosclerosis, arterio(lo)sclerosis, (micro)infarcts, and amyloid angiopathy play an important role alongside other markers of neurodegeneration. Cerebrovascular disease will be present in most individuals with dementia, but-just like other causes-rarely a cause on its own. The consequent limitations of nosology may be alleviated by addition of a vascular component to the recently introduced amyloid/tau/neurodegeneration etiological classification system for dementia. Meanwhile, risk of dementia is increased about 2-fold after stroke, and the prevention of (recurrent) stroke remains a cornerstone in the prevention of vascular dementia. Similarly, control of cardiovascular risk factors from middle age onwards is likely to have contributed to the reported decline in the age-specific incidence of dementia over the past decades. In conjunction with experimental studies, large-scale observational evidence from imaging, genomics, metabolomics, and alike will continue to improve our understanding of the underlying pathophysiological processes. To prevent ecological fallacies, such etiological studies in patients with dementia are best served by inclusion of subjects regardless of the presumed (single) cause of their disease.


Production and characterization of monoclonal antibodies specific for canine CD138 (syndecan-1) for nuclear medicine preclinical trials on spontaneous tumours.
We isolated 11 antibodies specific for canine CD138 (cCD138) to validate the interest of CD138 antigen targeting in dogs with spontaneous mammary carcinoma. The affinity of the monoclonal antibodies in the nanomolar range is suitable for immunohistochemistry and nuclear medicine applications. Four distinct epitopes were recognized on cCD138 by this panel of antibodies. CD138 expression in canine healthy tissues is comparable to that reported in humans. CD138 is frequently expressed in canine mammary carcinomas corresponding to the human triple negative breast cancer subtype, with cytoplasmic and membranous expression. In canine diffuse large B-cell lymphoma, CD138 expression is associated with the 'non-germinal center' phenotype corresponding to the most aggressive subtype in humans. This homology of CD138 expression between dogs and humans confirms the relevance of tumour-bearing dogs as spontaneous models for nuclear medicine applications, especially for the evaluation of new tumour targeting strategies for diagnosis by phenotypic imaging and radio-immunotherapy.


Reduced DICER1 Expression Bestows Rheumatoid Arthritis Synoviocytes Proinflammatory Properties and Resistance to Apoptotic Stimuli.
While the regulatory role of individual microRNAs (miRNAs) in rheumatoid arthritis (RA) is well established, the role of DICER1 in the pathogenesis of the disease has not yet been investigated. The purpose of this study was to analyze the expression of factors involved in miRNA biogenesis in fibroblast-like synoviocytes (FLS) from RA patients and to monitor the arthritis triggered by K/BxN serum transfer in mice deficient in the Dicer gene (Dicer(d/d) ). The expression of genes and precursor miRNAs was quantified by quantitative reverse transcription-polymerase chain reaction (qRT-PCR). MicroRNA macroarray profiling was monitored by qRT-PCR. Cytokines were quantified by enzyme-linked immunosorbent assay. Experimental arthritis in mice was achieved by the transfer of serum from K/BxN donors. Apoptosis was quantified using an enzyme-linked immunosorbent assay. We found decreased DICER1 and mature miRNA expression in synovial fibroblasts from RA patients. These cells were hyperresponsive to lipopolysaccharide, as evidenced by their increased interleukin-6 secretion upon stimulation. Experimental serum-transfer arthritis in Dicer(d/d) mice confirmed that an unbalanced biogenesis of miRNAs correlated with an enhanced inflammatory response. Synoviocytes from both RA patients and Dicer(d/d) mice exhibited increased resistance to apoptotic stimuli. The findings of this study further substantiate the important role of DICER1 in the maintenance of homeostasis and the regulation of inflammatory responses.


Risk factors for kerosene stove explosion burns seen at Kenyatta National Hospital in Kenya.
The kerosene stove is a common cooking appliance in lower and middle income households in Kenya and if it explodes, life threatening thermal burn injuries may be sustained by those using the appliance. Women tend to be victims more frequently since traditionally they are the ones who are involved in cooking. The aim of this study was to determine risk factors predisposing to kerosene stove explosion burns seen at Kenyatta National Hospital. The study was a prospective longitudinal descriptive study carried out at the Kenyatta National Hospital. Forty-eight patients who met the inclusion criteria were recruited into the study over a period of 6 months from November 2010 to April 2011 and the data was collected using a structured questionnaire. The analysis, using SPSS version 17.0 was done by associating occurrence of injury to: age, sex, socioeconomic status and level of education of patient. Charts and tables were used to present the results. The mean age of patients who sustained kerosene stove explosion burns was 23.6 years (SD ± 11.7) with the commonest age group being 20-39 years. More females were affected than males by a ratio of 7:3 and ninety two percent of those who sustained these burns were either from poor or lower middle socio-economic class. Stove explosions occurred mainly during cooking and when kerosene refill was being done. Most of the patients (63%) reported having bought kerosene from fuel vendors and almost all explosions were caused by the wick type of stove (98%). Young females from poor socioeconomic background were found to be at a higher risk for kerosene stove explosion burns. The wick stove is a common cause of burns especially when users unwittingly refill it with kerosene when already lit resulting in an explosion. Prevention can be done through evidence based public health education targeting the groups at risk and enactment of relevant laws.


Regulation of glucagon release in mouse -cells by KATP channels and inactivation of TTX-sensitive Na+ channels.
The perforated patch whole-cell configuration of the patch-clamp technique was applied to superficial glucagon-secreting alpha-cells in intact mouse pancreatic islets. alpha-cells were distinguished from the beta- and delta-cells by the presence of a large TTX-blockable Na+ current, a TEA-resistant transient K+ current sensitive to 4-AP (A-current) and the presence of two kinetically separable Ca2+ current components corresponding to low- (T-type) and high-threshold (L-type) Ca2+ channels. The T-type Ca2+, Na+ and A-currents were subject to steady-state voltage-dependent inactivation, which was half-maximal at -45, -47 and -68 mV, respectively. Pancreatic alpha-cells were equipped with tolbutamide-sensitive, ATP-regulated K+ (KATP) channels. Addition of tolbutamide (0.1 mM) evoked a brief period of electrical activity followed by a depolarisation to a plateau of -30 mV with no regenerative electrical activity. Glucagon secretion in the absence of glucose was strongly inhibited by TTX, nifedipine and tolbutamide. When diazoxide was added in the presence of 10 mM glucose, concentrations up to 2 microM stimulated glucagon secretion to the same extent as removal of glucose. We conclude that electrical activity and secretion in the alpha-cells is dependent on the generation of Na+-dependent action potentials. Glucagon secretion depends on low activity of KATP channels to keep the membrane potential sufficiently negative to prevent voltage-dependent inactivation of voltage-gated membrane currents. Glucose may inhibit glucagon release by depolarising the alpha-cell with resultant inactivation of the ion channels participating in action potential generation.


Childhood sexual abuse and HIV risk among crack-using commercial sex workers in San Salvador, El Salvador: a qualitative analysis.
This article explores the relationship between childhood sexual abuse (CSA) and later HIV risk. It draws on qualitative, in-depth interviews with 40 women who either used crack or engaged in commercial sex work in the greater metropolitan area of San Salvador, El Salvador, 28 of whom experienced CSA. Although the relationship between CSA and later HIV risk has been clearly demonstrated, the processes that lead women who have experienced CSA to experience HIV risk are unclear. The theoretical model presented here incorporates the psychological effects of CSA, particularly stigmatization, as well as its social consequences and the larger context of poverty in which these women live. The meanings women draw from past abuse experiences and their rationale for choices made help explain the association between CSA and later risk as mediated through sex work and crack addiction. Self-report data gathered in this study indicate that HIV prevalence may be considerably higher in this high-risk population than Salvadoran national rates.


Long-term safety, tolerability, and weight loss associated with metformin in the Diabetes Prevention Program Outcomes Study.
Metformin produced weight loss and delayed or prevented diabetes in the Diabetes Prevention Program (DPP). We examined its long-term safety and tolerability along with weight loss, and change in waist circumference during the DPP and its long-term follow-up. The randomized double-blind clinical trial of metformin or placebo followed by a 7-8-year open-label extension and analysis of adverse events, tolerability, and the effect of adherence on change in weight and waist circumference. No significant safety issues were identified. Gastrointestinal symptoms were more common in metformin than placebo participants and declined over time. During the DPP, average hemoglobin and hematocrit levels were slightly lower in the metformin group than in the placebo group. Decreases in hemoglobin and hematocrit in the metformin group occurred during the first year following randomization, with no further changes observed over time. During the DPP, metformin participants had reduced body weight and waist circumference compared with placebo (weight by 2.06 ± 5.65% vs. 0.02 ± 5.52%, P < 0.001, and waist circumference by 2.13 ± 7.06 cm vs. 0.79 ± 6.54 cm, P < 0.001 in metformin vs. placebo, respectively). The magnitude of weight loss during the 2-year double-blind period was directly related to adherence (P < 0.001). Throughout the unblinded follow-up, weight loss remained significantly greater in the metformin group than in the placebo group (2.0 vs. 0.2%, P < 0.001), and this was related to the degree of continuing metformin adherence (P < 0.001). Metformin used for diabetes prevention is safe and well tolerated. Weight loss is related to adherence to metformin and is durable for at least 10 years of treatment.


[Early detection of methicillin resistance by real-time PCR in staphylococci isolated from blood cultures].
Bacteremia caused by methicillin-resistant Staphylococcus aureus (MRSA) has a significant morbidity and mortality. The aim of this study was to evaluate the efficiency of real-time polymerase chain reaction (Rt-PCR) targeting nuc and mec genes in the culture extracts of blood culture systems for the early diagnosis of MRSA. A total of 48 samples that gave positive growth signal in BACTEC 9000 MB (BD, USA) and stained as gram-positive cocci, were included in the study. The samples were collected between 2009 and 2010. VITEC 2 (bioMerieux, France) system was used for the identification and antibiotic susceptibility testing of the isolates. According to the culture results, 15 of the isolates were methicillin-resistant coagulase-negative staphylococci (MRCNS), four were MRSA, 14 were methicillin-susceptible coagulase- negative staphylococci (MSCNS) and 15 were methicillin-susceptible S.aureus (MSSA). However, Rt-PCR yielded 17 MRCNS, eight MRSA, 10 MSCNS and 13 MSSA results. Our findings indicated lack of concordance between blood culture and PCR technique. When the blood culture results were accepted as the gold standard for the determination of methicillin resistance, sensitivity, specificity, positive and negative predictive values of Rt-PCR were found as 73%, 62%, 56% and 78%, respectively. In conclusion, in contrast to the expectations, Rt-PCR was not considered as an appropriate method for the detection of MRSA in routine diagnosis.


Inducing Differential Self-Assembling Behavior in Ultrashort Peptide Hydrogelators Using Simple Metal Salts.
Controlling the self-assembly pathways can be an effective means to create complex multifunctional structures based on a single gelator design. To this direction, an ion mediated approach to control and direct supramolecular structure of the low molecular weight peptide hydrogelator would be an excellent methodology for bottom-up nanofabrication of these advanced functional materials. Our work primarily aims to understand the role of different metal ions as well as anions in modulating the self-assembly of the peptide amphiphiles. Our approach relies on rational incorporation of histidine in the peptide amphiphile, which can impart an ion responsive behavior to the hydrogels. Interestingly, the self-assembly pathway of histidine based dipeptide amphiphile was found to be largely influenced by various metal salts. A gel to sol transition occurred at physiological pH in the presence of Cu2+, Ni2+ and Co2+ ions, owing to their strong interactions with the histidine, thus shifting the gelation to pH 3.0. However, in the case of Fe2+ and Mn2+, the weak interactions of histidine-metal ion can still hold the gel at physiological pH but gel strength was significantly decreased. Our studies provide a clear insight into this ion-responsive behavior across a wide pH range, which is mainly governed by the stability of a peptide-metal ion complex as per Irving-Williams series. Moreover, anions also influenced the mechanical strength as well as morphology of the nanostructures owing to their differential interaction with water as depicted in the Hofmeister series of anions. This bioinspired approach will provide an elegant strategy for accessing diverse structures, which are "out of equilibrium" and otherwise only accessible through differential molecular design. We envisage that our systematic studies on histidine-metal ion interaction can be an extremely useful methodology, which will pave a way to design and develop the stimuli responsive biomaterials.


Microneedle-based devices for point-of-care infectious disease diagnostics.
Recent infectious disease outbreaks, such as COVID-19 and Ebola, have highlighted the need for rapid and accurate diagnosis to initiate treatment and curb transmission. Successful diagnostic strategies critically depend on the efficiency of biological sampling and timely analysis. However, current diagnostic techniques are invasive/intrusive and present a severe bottleneck by requiring specialist equipment and trained personnel. Moreover, centralised test facilities are poorly accessible and the requirement to travel may increase disease transmission. Self-administrable, point-of-care (PoC) microneedle diagnostic devices could provide a viable solution to these problems. These miniature needle arrays can detect biomarkers in/from the skin in a minimally invasive manner to provide (near-) real-time diagnosis. Few microneedle devices have been developed specifically for infectious disease diagnosis, though similar technologies are well established in other fields and generally adaptable for infectious disease diagnosis. These include microneedles for biofluid extraction, microneedle sensors and analyte-capturing microneedles, or combinations thereof. Analyte sampling/detection from both blood and dermal interstitial fluid is possible. These technologies are in their early stages of development for infectious disease diagnostics, and there is a vast scope for further development. In this review, we discuss the utility and future outlook of these microneedle technologies in infectious disease diagnosis.


High grade intraepithelial neoplasia of prostate is associated with values of prostate specific antigen related parameters intermediate between prostate cancer and normal levels.
High grade prostatic intraepithelial neoplasia (HGPIN) is widely regarded as the precancerous. The aim of this study was to determine PSA related parameters in patients with initial PSA values 2-10 ng/mL and diagnosis of HGPIN without finding carcinoma at the time of their first needle biopsy. Study groups consisted of 100 men who were diagnosed HGPIN, 84 with cancer and 183 with benign hyperplasia on first biopsy of prostate. Total PSA and free PSA were measured and ratio free/total PSA and PSA density calculated. Mean values of these parameters were compared, and receiver operating characteristic curves were used for comparison of PSA related parameters to discriminate groups of patients.Total PSA, free PSA level and PSA density in patients with HGPIN (6.388 ng/mL) did not differ significantly compared to prostate carcinoma (6.976 ng/mL) or benign prostatic hyperplasia (6.07 ng/mL) patients. Patients with HGPIN had significantly higher ratio free/total PSA than those with prostate carcinoma (0.168 vs 0.133), but significantly lower than patients with benign prostatic hyperplasia (0.168 vs 0.185). Ratio of free/total PSA significantly discriminate HGPIN from prostate carcinoma with sensitivity 84.52 and specify 45.00 at cut-off point of ≤ 0.18. Values of PSA, free PSA and ratio free/total PSA in cases of HGPIN appear to be intermediate between prostate cancer and normal levels. Ratio of free/total PSA may help in decision to repeat biopsies in the presence of HGPIN on biopsy, without concomitant prostate cancer, in patients suitable for curative treatment, with normal digito-rectal examination and trans-rectal sonography.


Unification of sentence processing via ear and eye: an fMRI study.
We present new evidence based on fMRI for the existence and neural architecture of an abstract supramodal language system that can integrate linguistic inputs arising from different modalities such that speech and print each activate a common code. Working with sentence material, our aim was to find out where the putative supramodal system is located and how it responds to comprehension challenges. To probe these questions we examined BOLD activity in experienced readers while they performed a semantic categorization task with matched written or spoken sentences that were either well-formed or contained anomalies of syntactic form or pragmatic content. On whole-brain scans, both anomalies increased net activity over non-anomalous baseline sentences, chiefly at left frontal and temporal regions of heteromodal cortex. The anomaly-sensitive sites correspond approximately to those that previous studies (Michael et al., 2001; Constable et al., 2004) have found to be sensitive to other differences in sentence complexity (object relative minus subject relative). Regions of interest (ROIs) were defined by peak response to anomaly averaging over modality conditions. Each anomaly-sensitive ROI showed the same pattern of response across sentence types in each modality. Voxel-by-voxel exploration over the whole brain based on a cosine similarity measure of common function confirmed the specificity of supramodal zones.


Common mental disorders and the built environment in Santiago, Chile.
There is growing research interest in the influence of the built environment on mental disorders. To estimate the variation in the prevalence of common mental disorders attributable to individuals and the built environment of geographical sectors where they live. A sample of 3870 adults (response rate 90%) clustered in 248 geographical sectors participated in a household cross-sectional survey in Santiago, Chile. Independently rated contextual measures of the built environment were obtained. The Clinical Interview Schedule was used to estimate the prevalence of common mental disorders. There was a significant association between the quality of the built environment of small geographical sectors and the presence of common mental disorders among its residents. The better the quality of the built environment, the lower the scores for psychiatric symptoms; however, only a small proportion of the variation in common mental disorder existed at sector level, after adjusting for individual factors. Findings from our study, using a contextual assessment of the quality of the built environment and multilevel modelling in the analysis, suggest these associations may be more marked in non-Western settings with more homogeneous geographical sectors.


Prevalence and projections of diabetes and pre-diabetes in adults in Sri Lanka--Sri Lanka Diabetes, Cardiovascular Study (SLDCS).
To determine the prevalence of diabetes mellitus and pre-diabetes (impaired fasting glucose and impaired glucose tolerance) in adults in Sri Lanka. Projections for the year 2030 and factors associated with diabetes and pre-diabetes are also presented. This cross-sectional study was conducted between 2005 and 2006. A nationally representative sample of 5000 adults aged >or= 18 years was selected by a multi-stage random cluster sampling technique. Fasting plasma glucose was tested in all participants and a 75-g oral glucose tolerance test was performed in non-diabetic subjects. Prevalence was estimated for those > 20 years of age. Response rate was 91% (n = 4532), males 40%, age 46.1 +/- 15.1 years (mean +/- standard deviation). The age-sex standardized prevalence (95% confidence interval) of diabetes for Sri Lankans aged >or= 20 years was 10.3% (9.4-11.2%) [males 9.8% (8.4-11.2%), females 10.9% (9.7-12.1%), P = 0.129). Thirty-six per cent (31.9-40.1%) of all diabetic subjects were previously undiagnosed. Diabetes prevalence was higher in the urban population compared with rural [16.4% (13.8-19.0%) vs. 8.7% (7.8-9.6%); P < 0.001]. The prevalence of overall, urban and rural pre-diabetes was 11.5% (10.5-12.5%), 13.6% (11.2-16.0%) and 11.0% (10.0-12.0%), respectively. Overall, 21.8% (20.5-23.1%) had some form of dysglycaemia. The projected diabetes prevalence for the year 2030 is 13.9%. Those with diabetes and pre-diabetes compared with normal glucose tolerance were older, physically inactive, frequently lived in urban areas and had a family history of diabetes. They had higher body mass index, waist circumference, waist-hip ratio, systolic/diastolic blood pressure, low-density lipoprotein cholesterol and triglycerides. Insulin was prescribed to 4.4% (2.7-6.1%) of all diabetic subjects. One in five adults in Sri Lanka has either diabetes or pre-diabetes and one-third of those with diabetes are undiagnosed.


Difficult catheter access to the occluded vessel during endovascular treatment of acute ischemic stroke is associated with worse clinical outcome.
During endovascular procedures for acute ischemic stroke, catheter access to the occluded vessel may be technically difficult or impossible. The aim of this study was to access the impact of difficult catheter access to target the carotid artery on clinical outcome. Anterior circulation stroke patients undergoing transfemoral endovascular procedures where studied. Patients were divided into four groups according to time from groin puncture to target carotid catheterization quartiles. Patients in quartile 4 (Q4) were considered difficult carotid access. We defined several outcome measures: recanalisation (final Thrombolysis in Cerebral Infarction score ≥ 2a), time from groin puncture to recanalisation and favorable long term outcome (modified Rankin Scale score <3 at 3 months). Of 130 patients studied, carotid catheterization was impossible in seven patients (5.1%). These patients had significantly lower rates of recanalization (14.3% vs 80.5%; p<0.01) and favorable outcome (0% vs 36%; p=0.038). Among patients with an accessible carotid artery(n=123), median time from groin puncture to carotid catheterization was 20 min (IQR 10). A negative correlation between time to carotid access and recanalization was observed (r=-0.31; p<0.01). Patients in Q4 (>30 min) had lower rates of recanalization (60.7% vs 82.4%; p=0.02) and a lower favorable outcome (13.6% vs 41.3%; p=0.04). A logistic regression adjusted by age showed that baseline National Institutes of Health Stroke Scale score (OR 0.8; 95% CI: 0.72 to 0.92 p<0.01) and having difficult access (OR 1.3; 95% CI 1.3 to 20.1 p=0.018) independently predicted worse long term outcome. Difficult catheter access to target the carotid is common during acute endovascular treatment of stroke patients and is associated with a worse clinical outcome. If transfemoral access appears difficult, alternative access such as direct carotid puncture could be explored.


A general model of the public goods dilemma.
An individually costly act that benefits all group members is a public good. Natural selection favours individual contribution to public good [corrected] only when some benefit to the individual offsets the cost of contribution. Problems of sex ratio, parasite virulence, microbial metabolism, punishment of noncooperators, and nearly all aspects of sociality have been analysed as public goods shaped by kin and group selection. Here, I develop two general aspects of the public goods problem that have received relatively little attention. First, variation in individual resources favours selfish individuals to vary their allocation to public goods. Those individuals better endowed contribute their excess resources to public benefit, whereas those individuals with fewer resources contribute less to the public good. Thus, purely selfish behaviour causes individuals to stratify into upper classes that contribute greatly to public benefit and social cohesion and to lower classes that contribute little to the public good. Second, if group success absolutely requires production of the public good, then the pressure favouring production is relatively high. By contrast, if group success depends weakly on the public good, then the pressure favouring production is relatively weak. Stated in this way, it is obvious that the role of baseline success is important. However, discussions of public goods problems sometimes fail to emphasize this point sufficiently. The models here suggest simple tests for the roles of resource variation and baseline success. Given the widespread importance of public goods, better models and tests would greatly deepen our understanding of many processes in biology and sociality.


A new approach to population sizing for memetic algorithms: a case study for the multidimensional assignment problem.
Memetic algorithms are known to be a powerful technique in solving hard optimization problems. To design a memetic algorithm, one needs to make a host of decisions. Selecting the population size is one of the most important among them. Most of the algorithms in the literature fix the population size to a certain constant value. This reduces the algorithm's quality since the optimal population size varies for different instances, local search procedures, and runtimes. In this paper we propose an adjustable population size. It is calculated as a function of the runtime of the whole algorithm and the average runtime of the local search for the given instance. Note that in many applications the runtime of a heuristic should be limited and, therefore, we use this bound as a parameter of the algorithm. The average runtime of the local search procedure is measured during the algorithm's run. Some coefficients which are independent of the instance and the local search are to be tuned at the design time; we provide a procedure to find these coefficients. The proposed approach was used to develop a memetic algorithm for the multidimensional assignment problem (MAP). We show that our adjustable population size makes the algorithm flexible to perform efficiently for a wide range of running times and local searches and this does not require any additional tuning of the algorithm.


Utility of cone-beam computed tomography in the assessment of the porto-spleno-mesenteric venous system.
The common diagnostic tools available to evaluate the porto-spleno-mesenteric venous (PSMV) system provide either good hemodynamic information with limited morphological details [e.g., ultrasonography (US)] or excellent tomographic display of the anatomy with limited information about flow patterns [e.g., multidetector computed tomography (MDCT) and magnetic resonance imaging]. Although catheter-directed selective digital subtraction angiography (DSA) can provide excellent information about flow at a high temporal resolution and can generate images at a high spatial resolution, this technique is often limited by a lack of cross-sectional detail. In the assessment of the PSMV system, DSA is also limited by dilution of contrast and motion artefacts. Combining venous phase cone-beam computed tomography (CBCT) with DSA can generate high-quality tomographic data, which allows detailed evaluation of venous tributaries and flow patterns within the splenic, superior mesenteric, and inferior mesenteric venous systems individually. This enables clinicians to better understand the impact of nonobstructive resistance to flow (e.g., as in patients with cirrhosis) and obstructive resistance to flow (e.g., as in patients with thrombosis) within each system and plan treatment accordingly. In this review, we discuss the limitations of common diagnostic methods and the role venous CBCT in combination with DSA can play in assessing the PSMV system.


Brief report: Past, present, emergent and future identities of young inmates.
This study aims to investigate how young inmates integrate temporal and contextual elements of identity and what is the role of education in identity integration. Twenty-six young inmates were interviewed. Thematic analysis revealed that inmates integrated the elements of four time identities using different mechanisms to deal with each identity: (a) Past identity (before imprisonment) is defined by cumulative risk factors, where detachment from family, society, and institutions prevails; (b) present identity is characterized by the engagement in prison's educational activities; (c) emergent identity (until their release) is characterized by their requests for a proper education and training and their commitment to acquire qualifications; (d) future identity (after their release) is characterized by the investment on future aims for personal growth, family, education/work and community. Inmates used the non-formal educational program, which was offered in prison, as a vehicle towards positive identity contemplation.


Quantum computing on encrypted data.
The ability to perform computations on encrypted data is a powerful tool for protecting privacy. Recently, protocols to achieve this on classical computing systems have been found. Here, we present an efficient solution to the quantum analogue of this problem that enables arbitrary quantum computations to be carried out on encrypted quantum data. We prove that an untrusted server can implement a universal set of quantum gates on encrypted quantum bits (qubits) without learning any information about the inputs, while the client, knowing the decryption key, can easily decrypt the results of the computation. We experimentally demonstrate, using single photons and linear optics, the encryption and decryption scheme on a set of gates sufficient for arbitrary quantum computations. As our protocol requires few extra resources compared with other schemes it can be easily incorporated into the design of future quantum servers. These results will play a key role in enabling the development of secure distributed quantum systems.


Healthcare Encounter and Financial Impact of COVID-19 on Children's Hospitals.
Children's hospitals responded to COVID-19 by limiting nonurgent healthcare encounters, conserving personal protective equipment, and restructuring care processes to mitigate viral spread. We assessed year-over-year trends in healthcare encounters and hospital charges across US children's hospitals before and during the COVID-19 pandemic. We performed a retrospective analysis, comparing healthcare encounters and inflation-adjusted charges from 26 tertiary children's hospitals reporting to the PROSPECT database from February 1 to June 30 in 2019 (before the COVID-19 pandemic) and 2020 (during the COVID-19 pandemic). All children's hospitals experienced similar trends in healthcare encounters and charges during the study period. Inpatient bed-days, emergency department visits, and surgeries were lower by a median 36%, 65%, and 77%, respectively, per hospital by the week of April 15 (the nadir) in 2020 compared with 2019. Across the study period in 2020, children's hospitals experienced a median decrease of $276 million in charges.


Comparative genomic analysis of Geosporobacter ferrireducens and its versatility of anaerobic energy metabolism.
Members of the family Clostridiaceae within phylum Firmicutes are ubiquitous in various iron-reducing environments. However, genomic data on iron-reducing bacteria of the family Clostridiaceae, particularly regarding their environmental distribution, are limited. Here, we report the analysis and comparison of the genomic properties of Geosporobacter ferrireducens IRF9, a strict anaerobe that ferments sugars and degrades toluene under iron-reducing conditions, with those of the closely related species, Geosporobacter subterraneus DSM 17957. Putative alkyl succinate synthase-encoding genes were observed in the genome of strain IRF9 instead of the typical benzyl succinate synthase-encoding genes. Canonical genes associated with iron reduction were not observed in either genome. The genomes of strains IRF9 and DMS 17957 harbored genes for acetogenesis, that encode two types of Rnf complexes mediating the translocation of H+ and Na+ ions, respectively. Strain IRF9 harbored two different types of ATPases (Na+-dependent F-type ATPase and H+-dependent V-type ATPase), which enable full exploitation of ion gradients. The versatile energy conservation potential of strain IRF9 promotes its survival in various environmental conditions.


Root Resorption Classifications: A Narrative Review and a Clinical Aid Proposal for Routine Assessment.
Root resorption (RR) refers to noninfectious damage related to the loss of hard and soft dental tissue that results from clastic cell activity. It is observed as a pathologic process that is predominantly asymptomatic in the permanent dentition and physiological during the shedding of primary teeth. Roots are protected by unmineralized organic cementoid and predentine. RR occurs because of the inability of the clastic cells to adhere to unmineralized surfaces. Since the first RR classification was described by Andreasen in the 1970s, several classifications have been proposed with diverse terminology. A narrative literature review was undertaken on the current classification, diagnosis, pathophysiology, and treatment of RR. A bibliographic search resulted in 434 titles and abstracts, and from those, 17 articles were obtained that alluded to 15 RR classifications. A total of 28 articles that met the inclusion criteria were included. Results showed that Andreasen's classification is the most widely used for classifying RR. In terms of epidemiologic data, studies are scarce, although RR pathophysiology is well described in the literature. Overall clinical guidelines are summarized in a new RR classification diagram. The choice of RR treatment application should be in line with the RR type and the dentist's experience. However, an earlier and correct diagnosis will significantly improve final outcomes and long-term prognosis, especially with the current evolution of advanced imaging techniques, such as cone-beam computed tomography and bioceramic-based endodontic sealers.


Football incident analysis: a new video based method to describe injury mechanisms in professional football.
To develop and test a new video based method for match analysis that combines football specific and medical information to achieve a better understanding of the injury mechanisms and events leading up to high risk situations. Football incident analysis (FIA) is a video based method describing incidents that may result in an injury using 19 variables and categories modified from match analysis. Videos from 35 of 76 (46%) official Norwegian under 21 matches played from 1994 to 1998 were analysed. Two football experts classified each incident on the basis of predetermined criteria, and their results were compared using interobserver and intraobserver reliability tests. kappa correlation coefficients for interobserver and intraobserver agreement were very good for 63% and 95% and good for 37% and 5% of the variables respectively. Fifty two incidents were recorded (1.6 incidents per team per match or 94 per 1000 player hours), and 16 (31%) led to injuries (0.5 injuries per match or 29 injuries per 1000 player hours). FIA results showed that 28 incidents occurred while attacking in midfield zone 2 or the attacking zone, and 24 took place while defending in the defensive zone or midfield zone 1. Midfielders were exposed in 67% of the incidents, mainly in breakdown attacks or during long attacks by the opposing team. Of the 28 incidents during offence, only one was classified as having great potential to score a goal. Most incidents (70%) were the result of tackling duels both in the offensive and defensive playing phases. Of the 21 offensive incidents resulting from tackling duels, in 19 cases the exposed player was unaware of the tackling (passive duellist). This study shows that football incident analysis is a potentially valuable tool for understanding the events leading up to injuries in football.


Insulin-like growth factor I and leptin in umbilical cord plasma and infant birth size at term.
To determine the independent contributions to infant birth size of insulin-like growth factor I (IGF-I) and leptin measured in umbilical cord plasma. Umbilical cord blood was collected in 12 804 consecutive deliveries, and cord plasma from 585 singleton infants born at term after uncomplicated pregnancies was analyzed for leptin, IGF-I, and 2 IGF-binding proteins (IGFBP-1 and IGFBP-3). In multivariable analyses, we assessed maternal and infant covariates of leptin and IGF-I, and we evaluated the independent contribution of cord levels of leptin and IGF-I on infant birth size. Cord plasma levels of IGF-I were lower in women who reported smoking at the beginning of pregnancy compared with nonsmokers. In female infants, levels of IGF-I and leptin were higher than in male infants after adjustment for ponderal index and maternal factors. We found a strong parallel increase in umbilical IGF-I and leptin with increasing birth weight and birth length. For IGFBP-1, there was an opposite pattern: IGFBP-1 increased with decreasing birth size. The multivariable analysis, adjusted for length of gestation and maternal age, parity, prepregnancy weight, smoking during pregnancy, and offspring sex, showed that IGF-I and leptin, independent of each other, were associated with birth weight and birth length. Levels of IGF-I and leptin in umbilical cord plasma were higher in girls than in boys, but in both sexes, these 2 factors contributed independently and positively to birth weight and length. For IGFBP-1, high levels were associated with low birth weight and reduced length. If intrauterine growth is related to the risk of developing adult diseases, IGF-I, IGFBP-1, and leptin may be involved in the underlying processes.1131-1135 insulin like growth factors, leptin, umbilical cord plasma, birth weight.


Three-dimensional facial digitization using advanced digital image correlation.
Presented in this paper is an effective technique to acquire the three-dimensional (3D) digital images of the human face without the use of active lighting and artificial patterns. The technique is based on binocular stereo imaging and digital image correlation, and it includes two key steps: camera calibration and image matching. The camera calibration involves a pinhole model and a bundle-adjustment approach, and the governing equations of the 3D digitization process are described. For reliable pixel-to-pixel image matching, the skin pores and freckles or lentigines on the human face serve as the required pattern features to facilitate the process. It employs feature-matching-based initial guess, multiple subsets, iterative optimization algorithm, and reliability-guided computation path to achieve fast and accurate image matching. Experiments have been conducted to demonstrate the validity of the proposed technique. The simplicity of the approach and the affordable cost of the implementation show its practicability in scientific and engineering applications.


Perceived intensity of somatosensory cortical electrical stimulation.
Artificial sensations can be produced by direct brain stimulation of sensory areas through implanted microelectrodes, but the perceptual psychophysics of such artificial sensations are not well understood. Based on prior work in cortical stimulation, we hypothesized that perceived intensity of electrical stimulation may be explained by the population response of the neurons affected by the stimulus train. To explore this hypothesis, we modeled perceived intensity of a stimulation pulse train with a leaky neural integrator. We then conducted a series of two-alternative forced choice behavioral experiments in which we systematically tested the ability of rats to discriminate frequency, amplitude, and duration of electrical pulse trains delivered to the whisker barrel somatosensory cortex. We found that the model was able to predict the performance of the animals, supporting the notion that perceived intensity can be largely accounted for by spatiotemporal integration of the action potentials evoked by the stimulus train.


Riboflavin as an oral tracer for monitoring compliance in clinical research.
We studied urinary riboflavin as an objective biomarker of compliance in clinical research using a simplified method amenable to high throughput analysis. Six healthy women not taking vitamin supplements ingested a study pill containing riboflavin (32 mg) as an inactive tracer and the soy isoflavones daidzin (0.243 mmole) and genistin (0.222 mmole) as active ingredients once daily for four days. Riboflavin and metabolites of the isoflavones were measured in urine samples obtained before and after each pill. Urinary excretion of riboflavin and metabolites of both isoflavones peaked within 8 hrs and remained higher than baseline for 24 hrs. Urinary excretion of riboflavin was also measured in 152 additional women with unrestricted dietary supplement intakes. Mean and median urinary riboflavin concentrations in these women were 0.42 and 0.31 μg/mL, respectively, compared to 0.2 μg/mL during a riboflavin-restricted diet. Receiver operating characteristics (ROC) curves indicated that urinary riboflavin within 24 hrs after a 32 mg dose would perform well as a measure of compliance (all areas under the ROC curves ≥0.84. Samples collected during the initial 8 hrs after pill ingestion performed better as a compliance measure than later collections. In summary, compliance in a clinical study can be monitored in real time by incorporating 32 mg of riboflavin into study pills, with compliance indicated by urinary riboflavin levels increasing over individual baselines or to ≥1.0 μg/mL, with a false positive rate of being classified as compliant at <5%.


Epidemiologic and immunologic significance of age distribution of antibody to antigenic variants of influenza virus.
The effects on the antibody content of the population which result from repeated exposure to antigenic variants of influenza viruses have been studied by measuring, with many strains, the antibody content of lots of gamma globulin prepared in different years and the patterns of antibody found in sera collected in 1 year from various age groups. In all samples of gamma globulin collected from 1943 through 1951, high levels of antibody were found with strains of Type A and Type B influenza viruses isolated prior to 1941. The highest levels were found in the more recent collections of gamma globulin. Antibodies to A-prime, and to B strains of 1945 and 1952, were present at low levels in gamma globulin collected prior to the isolation of these viruses. A moderate increase in antibody was observed in the gamma globulin of recent years. The pattern of distribution of antibody by age found with most A-prime strains in serum pools exhibited high levels in infancy and childhood, but after the age of 20, little or no antibody was detected. With Type A strains antibody was usually not observed until the 11th year of age. Thereafter, high levels were present until age 20, when the amount of antibody declines to a moderate and relatively constant level which persists throughout life. Antibody against swine influenza virus did not become detectable until the 29th year. The intermediate antigenic character of a few A-prime isolates was reflected in the antibody pattern obtained with them. Antibody was not found until age 13 with the Lee (1940) strain of Type B influenza virus, but thereafter the level was high. With the type B isolates of 1945 and 1952, antibody became measurable at earlier ages. The present data clearly demonstrate that in the early years of life the range of the antibody spectrum is narrow, and that it becomes progressively broader in later life. A striking correlation was found between what is known of the periods of prevalence of certain strains of influenza viruses and the age of the people in whom strain-specific antibodies are currently found. It has been observed that the age at which antibodies to certain strains are first detectable has progressively advanced with the passage of time. From these data the following immunologic thesis is formulated. The antibody which is acquired during the initial infections of childhood is of limited scope and reflects the dominant antigens of the prevailing strains. The immunity conferred by the initial experiences with influenza is also limited. Successive experiences later in life with viruses of related but differing antigenic make-up result in a composite of antibody which is oriented toward a larger number of the common antigens which comprise influenza virus. These experiences confer a broader immunity which limits infection with, and antibody response to, the more recently encountered strains. The antibody-forming mechanisms appear to be oriented by the initial infections of childhood so that exposures later in life to antigenically related strains result in a progressive reinforcement of the primary antibody. The highest cumulative antibody levels detectable in a particular age group tend, therefore, to reflect the dominant antigens of the virus responsible for the childhood infections of that group. Hence the pattern of antibody distribution determined currently in different age groups provides a serologic recapitulation of past infection with antigenic variants of influenza viruses.


Craigslist versus print newspaper advertising for recruiting research participants for alcohol studies: Cost and participant characteristics.
Technology has transformed our lifestyles in dramatic and significant ways, including new and less expensive options for recruiting study participants. This study examines cost and participant differences between two recruitment sources, Craigslist (CL), and print newspapers (PNs). This paper also reviewed and compared studies involving clinical trials published since 2010 that recruited participants using CL alone or in combination with other methods. Secondary data analyses from a parent study involving a randomized controlled trial of a mail-based intervention to promote self-change with problem drinkers. Significant differences were found between CL and PN participants on most demographic and pretreatment drinking variables. While all participants had AUDIT scores suggestive of an alcohol problem and reported drinking at high-risk levels, CL participants had less severe drinking problem histories, were considerably younger, and had a higher socioeconomic status than PN participants. The total advertising costs for the 65 CL ads ($275) were significantly less than the 69 PN ads ($33, 311). The recruiting cost per eligible participant was vastly less expensive using CL ($1.46) compared to print newspaper ads ($116.88). Using CL is a viable recruitment method for soliciting participants, particularly those that are younger, for alcohol intervention studies. It is also less expensive than newspaper ads. When CL participants were recruited, they reported being slightly more confident to change their drinking than PN participants. Limitations of using CL are discussed, including that some initial ad responders gave inconsistent answers to similar questions and a few tried to enter the study more than once.