The plant stress hormone ethylene controls floral transition via DELLA-dependent regulation of floral meristem-identity genes.
The length of the Arabidopsis thaliana life cycle depends on the timing of the floral transition. Here, we define the relationship between the plant stress hormone ethylene and the timing of floral initiation. Ethylene signaling is activated by diverse environmental stresses, but it was not previously clear how ethylene regulates flowering. First, we show that ethylene delays flowering in Arabidopsis, and that this delay is partly rescued by loss-of-function mutations in genes encoding the DELLAs, a family of nuclear gibberellin (GA)-regulated growth-repressing proteins. This finding suggests that ethylene may act in part by modulating DELLA activity. We also show that activated ethylene signaling reduces bioactive GA levels, thus enhancing the accumulation of DELLAs. Next, we show that ethylene acts on DELLAs via the CTR1-dependent ethylene response pathway, most likely downstream of the transcriptional regulator EIN3. Ethylene-enhanced DELLA accumulation in turn delays flowering via repression of the floral meristem-identity genes LEAFY (LFY) and SUPPRESSOR OF OVEREXPRESSION OF CONSTANS 1 (SOC1). Our findings establish a link between the CTR1/EIN3-dependent ethylene and GA-DELLA signaling pathways that enables adaptively significant regulation of plant life cycle progression in response to environmental adversity.


Does physical activity influence semantic memory activation in amnestic mild cognitive impairment?
The effect of physical activity (PA) on functional brain activation for semantic memory in amnestic mild cognitive impairment (aMCI) was examined using event-related functional magnetic resonance imaging during fame discrimination. Significantly greater semantic memory activation occurred in the left caudate of High- versus Low-PA patients, (P=0.03), suggesting PA may enhance memory-related caudate activation in aMCI.


Efficacy and safety profile of COVID-19 vaccine in cancer patients: a prospective, multicenter cohort study.
Aim: To compare the seropositivity rate of cancer patients with noncancer controls after inactive SARS-CoV-2 vaccination and evaluate the factors affecting seropositivity. Method: Spike IgG antibodies against SARS-CoV-2 were measured in blood samples of 776 cancer patients and 715 noncancer volunteers. An IgG level ≥50 AU/ml is accepted as seropositive. Results: The seropositivity rate was 85.2% in the patient group and 97.5% in the control group. The seropositivity rate and antibody levels were significantly lower in the patient group (p < 0.001). Age and chemotherapy were associated with lower seropositivity in cancer patients (p < 0.001). Conclusion: This study highlighted the efficacy and safety of the inactivated vaccine in cancer patients. Clinical Trials Registration: NCT04771559 (ClinicalTrials.gov).


Characterization of the turning response of dorsal root neurites toward nerve growth factor.
This study reports that chick dorsal root ganglion neurites undergo a rapid (20 min) reorientation of their direction of growth in response to nerve growth factor (NGF) concentration gradients in vitro. Dorsal root ganglia from chick embryos were explanted onto a collagen-poly-L-lysine substrate. After 24-48 h in culture, NGF gradients were applied to individual growth cones via a micropipette containing 50 biological units NGF/ml. The growth cones turned and grew toward these NGF sources. This turning response was not caused by the trophic effects of NGF on neurite initiation, survival, or growth rate. Dorsal root neurites also grew toward sources of mono- and dibutyryl cyclic adenosine monophosphate (dB cAMP), cyclic guanosine monophosphate (cGMP), and elevated calcium in the presence of the calcium ionophore A23187. These results are consistent with the hypothesis that intracellular levels of cAMP and /or cGMP and calcium may play a role in the turning response of dorsal root neurites toward NGF, but do not establish a causal relationship between the mechanisms of action of NGF, cyclic nucleotides and calcium. Total growth cone adherence to the substrate was measured using a timed microjet of perfusion medium. NGF increased the adherence of growth cones to the substrate, but caffeine and dB cAMP which also elicit the positive turning response, decreased growth cone adherence. Calcium, which did not elicit the positive turning response, produced a greater growth cone adherence to the substrate than that observed with NGF. Although these results do not rule out a role of adhesion changes in axonal turning to NGF, they show that a general increase in adherence does not correlate well with the rapid turning response observed in this study.


Auricular acupuncture: a potential treatment for anxiety.
Acupuncture can be an effective treatment for chronic anxiety disorders. The purpose of this study was to assess the effectiveness of acupuncture in reducing anxiety in a volunteer population. If found effective, this modality could be introduced as a treatment of anxiety before surgery. Adult volunteers (n = 55), were randomized to three treatment groups: a) Shenmen group--bilateral auricular acupuncture at the "shenmen" point; b) Relaxation group-bilateral auricular acupuncture at a "relaxation" point; and c) Sham group-bilateral auricular acupuncture at a "sham" point. Press-acupuncture needles were inserted at the respective auricular areas for 48 h. State anxiety, blood pressure, heart rate, and electrodermal activity were assessed at 30 min, 24 h, and 48 h after insertion. Analyzing anxiety levels using repeated-measures analysis of variance has demonstrated a significant difference [F (2,51) =8.8, P = 0.001] between the three treatment groups. Post hoc analysis demonstrated that patients in the Relaxation group were significantly less anxious at 30 min (P = 0.007) and 24 h (P = 0.035) as compared with patients in both the Shenmen group and the Sham group, and less anxious at 48 h (P = 0.042) as compared with patients in Shenmen group. Repeated-measures analysis of variance performed for electrodermal activity, blood pressure, and heart rate demonstrated no group differences (P = ns). We conclude that auricular acupuncture at the "relaxation" point can decrease the anxiety level in a population of healthy volunteers.


Crowdsourcing malaria parasite quantification: an online game for analyzing images of infected thick blood smears.
There are 600,000 new malaria cases daily worldwide. The gold standard for estimating the parasite burden and the corresponding severity of the disease consists in manually counting the number of parasites in blood smears through a microscope, a process that can take more than 20 minutes of an expert microscopist's time. This research tests the feasibility of a crowdsourced approach to malaria image analysis. In particular, we investigated whether anonymous volunteers with no prior experience would be able to count malaria parasites in digitized images of thick blood smears by playing a Web-based game. The experimental system consisted of a Web-based game where online volunteers were tasked with detecting parasites in digitized blood sample images coupled with a decision algorithm that combined the analyses from several players to produce an improved collective detection outcome. Data were collected through the MalariaSpot website. Random images of thick blood films containing Plasmodium falciparum at medium to low parasitemias, acquired by conventional optical microscopy, were presented to players. In the game, players had to find and tag as many parasites as possible in 1 minute. In the event that players found all the parasites present in the image, they were presented with a new image. In order to combine the choices of different players into a single crowd decision, we implemented an image processing pipeline and a quorum algorithm that judged a parasite tagged when a group of players agreed on its position. Over 1 month, anonymous players from 95 countries played more than 12,000 games and generated a database of more than 270,000 clicks on the test images. Results revealed that combining 22 games from nonexpert players achieved a parasite counting accuracy higher than 99%. This performance could be obtained also by combining 13 games from players trained for 1 minute. Exhaustive computations measured the parasite counting accuracy for all players as a function of the number of games considered and the experience of the players. In addition, we propose a mathematical equation that accurately models the collective parasite counting performance. This research validates the online gaming approach for crowdsourced counting of malaria parasites in images of thick blood films. The findings support the conclusion that nonexperts are able to rapidly learn how to identify the typical features of malaria parasites in digitized thick blood samples and that combining the analyses of several users provides similar parasite counting accuracy rates as those of expert microscopists. This experiment illustrates the potential of the crowdsourced gaming approach for performing routine malaria parasite quantification, and more generally for solving biomedical image analysis problems, with future potential for telediagnosis related to global health challenges.


Determination of stroke volume by means of electrical impedance tomography.
ECG-gated electrical impedance tomography (EIT) is a non-invasive imaging technique, developed to monitor blood volume changes. This study is the first in comparing this non-invasive technique in measuring stroke volume with established techniques. The objective of this study was to validate EIT variables derived from the EIT images with paired obtained stroke volume measurements by thermodilution and MRI. After right cardiac catheterization, EIT measurements were performed in 25 patients. Regression analysis was used to analyse the relation between the EIT results and stroke volume determined by thermodilution. From the regression line an equation was derived to estimate stroke volume (in ml) by EIT. A strong correlation was found between EIT and stroke volume measured by the thermodilution method (r = 0.86). In a group of 11 healthy subjects this equation was validated to MRI. The mean and standard deviation of the difference between EIT and MRI was 0.7 ml and 5.4 ml respectively. These data indicate that EIT is a valid and reproducible method for the assessment of stroke volume.


Natural variation at sympathy for the ligule controls penetrance of the semidominant Liguleless narrow-R mutation in Zea mays.
Leaf architecture determines plant structural integrity, light harvesting, and economic considerations such as plant density. Ligules, junctions at the leaf sheath and blade in grasses, protect stalks from environmental stresses and, in conjunction with auricles, controls leaf angle. Previous studies in mutants have recessive liguleless mutants (lg1 and lg2) and dominant mutations in knotted1-like homeobox genes (Lg3-O, Lg4, and Kn1) involved in ligule development. Recently, a new semidominant liguleless mutant, Liguleless narrow (Lgn-R), has been characterized in maize that affects ligule and auricle development and results in a narrow leaf phenotype. We show that quantitative genetic variation affects penetrance of Lgn-R. To examine the genetic architecture underlying Lgn-R expressivity, crosses between Lgn-R/+ mutants in a B73 background and intermated B73 x Mo17 recombinant inbred lines were evaluated in multiple years and locations. A single main-effect quantitative trait locus (QTL) on chromosome 1 (sympathy for the ligule; sol) was discovered with a Mo17-contributed allele that suppressed Lgn-R mutant phenotypes. This QTL has a genetic-interaction with a locus on chromosome 7 (lucifer; lcf) for which the B73-contributed allele increases the ability of the sol(Mo17) allele to suppress Lgn-R. Neither of the genetic intervals likely to contain sol or lcf overlap with any current liguleless genes nor with previously identified genome-wide association QTL connected to leaf architecture. Analysis of phenotypes across environments further identified a genotype by enviroment interaction determining the strength of the sol x lcf interaction.


Hydrofluoric acid burns: a 15-year experience.
Hydrofluoric acid (HF) is a strong inorganic acid commonly used in many domestic and industrial settings. It is one of the most common chemical burns encountered in a burn center and frequently engenders controversy in its management. We report our 15 year experience with management of HF burns. We reviewed our experience from 1990 to 2005 for patients admitted with HF burns. Primary treatment was with calcium gluconate gel. Arterial infusion of calcium and fingernail removal were reserved for unrelenting symptoms. There were 7944 acute burn admissions to our center during this study period, 204 of which were chemical burns. HF burns comprised 17% of these chemical burn admissions (35 patients). All were men, with a mean burn size of 2.1 +/- 1.5% (range, 1-6%) and hospital stay of 1.6 +/- 0.7 days (range, 0-3 days). The most common seasonal time of injury was in the summer. Twelve patients (34%) were admitted to the intensive care unit for a total of 14 intensive care unit days, primarily for arterial infusions. Ventilator support was not required in any patient. No electrolyte abnormalities occurred. All burns were either partial thickness or small full thickness with no operative intervention required and no deaths. The upper extremity was most commonly involved (29 patients, 83%). The most common cause was air conditioner cleaner (8 patients, 23%). HF is a common cause of chemical burns. Although hospital admission is usually required for vigorous treatment and pain control, burn size is usually small and does not cause electrolyte abnormalities, significant morbidity, or death.


Whole-Genome Sequencing of the Opportunistic Yeast Pathogen Candida inconspicua Uncovers Its Hybrid Origin.
Fungal infections such as those caused by Candida species are increasingly common complications in immunocompromised patients. The list of causative agents of candidiasis is growing and comprises a set of emerging species whose relative global incidence is rare but recurrent. This is the case of Candida inconspicua, which prevalence has increased 10-fold over the last years. To gain novel insights into the emergence of this opportunistic pathogen and its genetic diversity, we performed whole genome sequencing of the type strain (CBS180), and of 10 other clinical isolates. Our results revealed high levels of genetic heterozygosity structured in non-homogeneous patterns, which are indicative of a hybrid genome shaped by events of loss of heterozygosity (LOH). All analyzed strains were hybrids and could be clustered into two distinct clades. We found large variability across strains in terms of ploidy, patterns of LOH, and mitochondrial genome heterogeneity that suggest potential admixture between hybrids. Altogether, our results identify a new hybrid species with virulence potential toward humans and underscore the potential role of hybridization in the emergence of novel pathogenic lineages.


Stochastic Vector Techniques in Ground-State Electronic Structure.
We review a suite of stochastic vector computational approaches for studying the electronic structure of extended condensed matter systems. These techniques help reduce algorithmic complexity, facilitate efficient parallelization, simplify computational tasks, accelerate calculations, and diminish memory requirements. While their scope is vast, we limit our study to ground-state and finite temperature density functional theory (DFT) and second-order many-body perturbation theory. More advanced topics, such as quasiparticle (charge) and optical (neutral) excitations and higher-order processes, are covered elsewhere. We start by explaining how to use stochastic vectors in computations, characterizing the associated statistical errors. Next, we show how to estimate the electron density in DFT and discuss effective techniques to reduce statistical errors. Finally, we review the use of stochastic vectors for calculating correlation energies within the second-order Møller-Plesset perturbation theory and its finite temperature variational form. Example calculation results are presented and used to demonstrate the efficacy of the methods.


Extracellular vesicles and their nucleic acids for biomarker discovery.
Extracellular vesicles (EVs) are a heterogenous population of vesicles originate from cells. EVs are found in different biofluids and carry different macromolecules, including proteins, lipids, and nucleic acids, providing a snap shot of the parental cells at the time of release. EVs have the ability to transfer molecular cargoes to other cells and can initiate different physiological and pathological processes. Mounting lines of evidence demonstrated that EVs' cargo and machinery is affected in disease states, positioning EVs as potential sources for the discovery of novel biomarkers. In this review, we demonstrate a conceptual overview of the EV field with particular focus on their nucleic acid cargoes. Current knowledge of EV subtypes, nucleic acid cargo and pathophysiological roles are outlined, with emphasis placed on advantages against competing analytes. We review the utility of EVs and their nucleic acid cargoes as biomarkers and critically assess the newly available advances in the field of EV biomarkers and high throughput technologies. Challenges to achieving the diagnostic potential of EVs, including sample handling, EV isolation, methodological considerations, and bioassay reproducibility are discussed. Future implementation of 'omics-based technologies and integration of systems biology approaches for the development of EV-based biomarkers and personalized medicine are also considered.


Toll-like receptors, innate immunity and HSV pathogenesis.
In the last decade, substantial progress has been made in understanding the molecular mechanisms involved in initial host responses to viral infections, and how viral recognition leads to the innate responses that ultimately shape the adaptive immune response. Viruses, including herpes simplex virus (HSV) types 1 and 2, trigger toll-like receptors (TLRs) that elicit cytokine and chemokine production. In turn, this can create local resistance and modulate T- and B-cell-mediated immunity. TLR activation by HSV-produced molecules (or other synthetic agonists) leads to the remodelling of draining lymph nodes. This enhances the screening of naive T-cells, from which antigen-specific lymphocytes can be selected and expanded. The innate response thereby serves to direct a timely and effective acquired immune response, through the initial TLR recognition of viral pathogen-associated molecular patterns that can limit or possibly exacerbate viral pathogenesis. Recently, these findings have been exploited by strategies that utilize synthetic TLR agonists as prophylactic or therapeutic devices. Such devices prime innate immune responses, enhancing host resistance to viral infections, including experimental HSV infections.


The efficacy of subcutaneous sumatriptan in the treatment of recurrence of migraine headache.
To investigate the efficacy of a second subcutaneous dose of 6 mg sumatriptan in the treatment of recurrence of headache after successful treatment of a migraine attack with an initial 6 mg dose. In a prospective, randomised, placebo controlled, double blind, parallel group study, 803 patients were treated for one to three migraine attacks with severe or moderate headache with a subcutaneous injection of 6 mg sumatriptan. Any subsequent recurrence of migraine headache was treated with a randomised second injection of sumatriptan or placebo. Recurrence was defined as a headache of moderate or severe intensity occurring 1-24 hours after the initial dose in a patient whose headache had been relieved by sumatriptan (reduction of headache severity from severe or moderate to mild or none after one hour). Headache recurrence was reported by 10%-15% of patients. At each attack, 6 mg sumatriptan given subcutaneously was significantly (P < 0.0005) more effective than placebo at relieving recurrent headache after one hour (84%-93% v 31%-50% of patients); 76%-83% of patients reported headache relief one hour after the initial dose of sumatriptan. Sumatriptan was generally well tolerated. Up to 15% of patients with migraine experience significant recurrence of headache after successful treatment with subcutaneous sumatriptan, and this recurrence is effectively treated by a further dose of subcutaneous sumatriptan.


Low prevalence of known pathogenic mutations in dominant PD genes: A Swedish multicenter study.
To determine the frequency of mutations known to cause autosomal dominant Parkinson disease (PD) in a series with more than 10% of Sweden's estimated number of PD patients. The Swedish Parkinson Disease Genetics Network was formed as a national multicenter consortium of clinical researchers who together have access to DNA from a total of 2,206 PD patients; 85.4% were from population-based studies. Samples were analyzed centrally for known pathogenic mutations in SNCA (duplications/triplications, p.Ala30Pro, p.Ala53Thr) and LRRK2 (p.Asn1437His, p.Arg1441His, p.Tyr1699Cys, p.Gly2019Ser, p.Ile2020Thr). We compared the frequency of these mutations in Swedish patients with published PD series and the gnomAD database. A family history of PD in first- and/or second-degree relatives was reported by 21.6% of participants. Twelve patients (0.54%) carried LRRK2 p.(Gly2019Ser) mutations, one patient (0.045%) an SNCA duplication. The frequency of LRRK2 p.(Gly2019Ser) carriers was 0.11% in a matched Swedish control cohort and a similar 0.098% in total gnomAD, but there was a marked difference between ethnicities in gnomAD, with 42-fold higher frequency among Ashkenazi Jews than all others combined. In relative terms, the LRRK2 p.(Gly2019Ser) variant is the most frequent mutation among Swedish or international PD patients, and in gnomAD. SNCA duplications were the second most common of the mutations examined. In absolute terms, however, these known pathogenic variants in dominant PD genes are generally very rare and can only explain a minute fraction of familial aggregation of PD. Additional genetic and environmental mechanisms may explain the frequent co-occurrence of PD in close relatives.


Agonistic and antagonistic effects of zearalenone, an etrogenic mycotoxin, on SKN, HHUA, and HepG2 human cancer cell lines.
Zearalenone (ZEA) is a nonsteroidal estrogenic compound mainly produced by the molds Fusarium graminearium and Fusarium culmorum found in a variety of host plants and soil debris around the world. ZEA is usualy non-lethal to animals but is important to livestock producers because its hyperestrogenic effects adversely influence the reproductive performance of animals. There have been suggestions of possible involvement of ZEA in the progression of breast malignancies and tumors of the female reproductive tract in humans. The toxic or stimulatory effects of ZEA and its metabolites alpha-zearalenol and 17-beta-estradiol on SKN, HHUAand HepG2 cells were studied using rapid colorimetric MTT assay. In general, both concentrations of 17-beta-estradiol (100M and 10 nM) were toxic to SKN and HHUA cell cultures. Both ZEA and alpha-zearalenol stimulated the proliferation of SKN and HHUA cells. On HepG2 cells, lower concentrations (10 nM) of 17-beta-estradiol and higher concentrations (100 microM) of ZEA exhibited toxic effects, whereas treatment with higher concentrations of 17-beta-estradiol and lower concentration of ZEA did not show toxic effects. A dose dependent antagonistic effect was observed when the cell cultures were pre-incubated with ICI 182,780, a synthetic estrogen receptor blocker, before estradiol or mycotoxin treatments.


Production of a gonadotropin-releasing hormone 2 receptor knockdown (GNRHR2 KD) swine line.
Swine are the only livestock species that produce both the second mammalian isoform of gonadotropin-releasing hormone (GNRH2) and its receptor (GNRHR2). Previously, we reported that GNRH2 and GNRHR2 mediate LH-independent testosterone secretion from porcine testes. To further explore this ligand-receptor complex, a pig model with reduced GNRHR2 expression was developed. Small hairpin RNA sequences targeting porcine GNRHR2 were subcloned into a lentiviral-based vector, lentiviral particles were generated and microinjected into the perivitelline space of zygotes, and embryos were transferred into a recipient. One GNRHR2 knockdown (KD) female was born that subsequently produced 80 piglets from 6 litters with 46 hemizygous progeny (57% transgenic). Hemizygous GNRHR2 KD (n = 10) and littermate control (n = 7) males were monitored at 40, 100, 150, 190, 225 and 300 days of age; body weight and testis size were measured and serum was isolated and assayed for testosterone and luteinizing hormone (LH) concentrations. Body weight of GNRHR2 KD boars was not different from littermate controls (P = 0.14), but testes were smaller (P < 0.05; 331.8 vs. 374.8 cm3, respectively). Testosterone concentrations tended (P = 0.06) to be reduced in GNRHR2 KD (1.6 ng/ml) compared to littermate control (4.2 ng/ml) males, but LH levels were similar (P = 0.47). The abundance of GNRHR2 mRNA was reduced (P < 0.001) by 69% in testicular tissue from mature GNRHR2 KD (n = 5) versus littermate control (n = 4) animals. These swine represent the first genetically-engineered model to elucidate the function of GNRH2 and its receptor in mammals.


Disparate distribution of hepatitis B virus genotypes in four sub-Saharan African countries.
Hepatitis B virus (HBV) places a substantial health burden on Africa. Here, we investigated genetic diversity of HBV variants circulating in 4 countries of sub-Saharan Africa using archived samples. In total, 1492 plasma samples were tested from HIV-infected individuals and pregnant women, among which 143 (9.6%) were PCR-positive for HBV DNA (Côte d'Ivoire, 70/608 [11.5%]; Ghana, 13/444 [2.9%]; Cameroon, 33/303 [10.9%]; and Uganda, 27/137 [19.7%]). Phylogenetic analysis of the S-gene sequences identified HBV genotypes E (HBV/E, n=96) and A (HBV/A, n=47) distributed as follows: 87% of HBV/E and 13% of HBV/A in Côte d'Ivoire; 100% of HBV/E in Ghana; 67% of HBV/E and 33% of HBV/A in Cameroon; and 100% of HBV/A in Uganda. The average and maximal nucleotide distances among HBV/E sequences were 1.9% and 6.4%, respectively, suggesting a greater genetic diversity for this genotype than previously reported (p<0.001). HBV/A strains were classified into subgenotypes HBV/A1, HBV/A2 and HBV/A3. In Uganda, 93% of HBV/A strains belonged to HBV/A1 whereas HBV/A3 was the only subgenotype of HBV/A found in Cameroon. In Côte d'Ivoire, HBV/A strains were classified as HBV/A1 (11.1%), HBV/A2 (33.3%) and HBV/A3 (55.6%). Phylogeographic analysis of the sequences available from Africa supported earlier suggestions on the origin of HBV/A1, HBV/A2 and HBV/A3 in East, South and West/Central Africa, respectively. Using predicted amino acid sequences, hepatitis B surface antigen (HBsAg) was classified into serotype ayw4 in 93% of HBV/E strains and adw2 in 68% of HBV/A strains. Also, 7.7% of the sequences carried substitutions in HBsAg associated with immune escape. The observations of pan-African and global dissemination of HBV/A1 and HBV/A2, and the circulation of HBV/E and HBV/A3 almost exclusively in West and Central Africa suggest a more recent increase in prevalence in Africa of HBV/E and HBV/A3 compared to HBV/A1 and HBV/A2. The broad genetic heterogeneity of HBsAg detected here may impact the efficacy of prevention and control efforts in sub-Saharan Africa.


The impact of the National Patient Safety Agency intravenous fluid alert on iatrogenic hyponatraemia in children.
In March 2007, the National Patient Safety Agency (NPSA) issued an alert regarding intravenous fluid (IVF) prescription to hospitalised infants and children, to be implemented in UK hospitals by September 2007. Previously, the most commonly used IVF (0.18% saline/4% dextrose) has been associated with iatrogenic hyponatraemia, resulting in four deaths and one near miss since 2000. The alert recommended 0.45% (or 0.9%) saline/5% dextrose as maintenance IVF and banned 0.18% saline/4% dextrose. We audited practice and outcome in children receiving maintenance IVF in June 2007 (before guideline implementation) and June 2008 (after guideline implementation). In June 2007, 44 (30%) children were prescribed IVF, six received IVF not recommended by NPSA alert 22 and one became hyponatraemic. In June 2008, 56 (30%) children received IVF; one received IVF not recommended by NPSA alert 22 and became hyponatraemic. The median change in serum sodium levels for all children who received IVF not recommended by NPSA alert 22 [-5 (-15 to 0) mmol/l] was significantly greater than those who received IVF recommended by NPSA alert 22 [0 (-13 to +7) mmol/l, p = 0.002]. In addition, there was a significant (p = 0.04) reduction in the number of children who had electrolytes checked while on IVF after implementation of the guideline. Implementation of a new IVF guideline has been associated with less use of IVF not recommended by NPSA alert 22, resulting in less serum sodium level reduction. The only children who became hyponatraemic received IVF not recommended by NPSA alert 22. Despite the NPSA alert and guideline implementation, less children had electrolyte levels checked while receiving IVF.


Efficacy and safety of lenalidomide for refractory cutaneous lupus erythematosus.
Cutaneous lupus erythematosus (CLE) is a chronic disease characterized by disfigurement and a relapsing course. Thalidomide has proven its efficacy in refractory cutaneous lupus disease, although it is not exempt from significant side effects and frequent relapses after withdrawal. New thalidomide analogues have been developed but lack clinical experience. The aim of this preliminary phase II study was to evaluate the efficacy and safety of lenalidomide in patients with refractory CLE. Fifteen patients with refractory cutaneous lupus disease were enrolled in this single-center, open-label, non-comparative pilot trial between January 2009 and December 2010. Oral lenalidomide (5 to 10 mg/day) was administered and tapered according to clinical response. Patients were followed up for a mean of 15 months (range: 7 to 30). Primary efficacy endpoint was the proportion of patients achieving complete response, defined by a Cutaneous Lupus Erythematosus Disease Area and Severity index (CLASI) activity score of 0. Other secondary endpoints included development of side effects, evaluation of cutaneous and systemic flares, and impact on the immunological parameters. One patient discontinued treatment due to side effects. All remaining patients saw clinical improvement and this was already noticeable after 2 weeks of treatment. Twelve of those patients (86%) achieved complete response but clinical relapse was frequent (75%), usually occurring 2 to 8 weeks after lenalidomide's withdrawal. No influence on systemic disease, immunological parameters or CLASI damage score was observed. Side effects including insomnia, grade 2 neutropenia and gastrointestinal symptoms, were minor (13%). These resolved after withdrawing medication. Neither polyneuropathy nor thrombosis was observed. Lenalidomide appears to be efficacious and safe in patients with refractory CLE, but clinical relapse is frequent after its withdrawal. ClinicalTrials.gov: NCT01408199.


A dataset of egg size and shape from more than 6,700 insect species.
Offspring size is a fundamental trait in disparate biological fields of study. This trait can be measured as the size of plant seeds, animal eggs, or live young, and it influences ecological interactions, organism fitness, maternal investment, and embryonic development. Although multiple evolutionary processes have been predicted to drive the evolution of offspring size, the phylogenetic distribution of this trait remains poorly understood, due to the difficulty of reliably collecting and comparing offspring size data from many species. Here we present a dataset of 10,449 morphological descriptions of insect eggs, with records for 6,706 unique insect species and representatives from every extant hexapod order. The dataset includes eggs whose volumes span more than eight orders of magnitude. We created this dataset by partially automating the extraction of egg traits from the primary literature. In the process, we overcame challenges associated with large-scale phenotyping by designing and employing custom bioinformatic solutions to common problems. We matched the taxa in this dataset to the currently accepted scientific names in taxonomic and genetic databases, which will facilitate the use of these data for testing pressing evolutionary hypotheses in offspring size evolution.


Barriers inhibiting effective detection and management of postpartum hemorrhage during facility-based births in Madagascar: findings from a qualitative study using a behavioral science lens.
Postpartum hemorrhage (PPH) is the leading cause of maternal mortality in low-income countries, and is the most common direct cause of maternal deaths in Madagascar. Studies in Madagascar and other low-income countries observe low provider adherence to recommended practices for PPH prevention and treatment. Our study addresses gaps in the literature by applying a behavioral science lens to identify barriers inhibiting facility-based providers' consistent following of PPH best practices in Madagascar. In June 2019, we undertook a cross-sectional qualitative research study in peri-urban and rural areas of the Vatovavy-Fitovinany region of Madagascar. We conducted 47 in-depth interviews in 19 facilities and five communities, with facility-based healthcare providers, postpartum women, medical supervisors, community health volunteers, and traditional birth attendants, and conducted thematic analysis of the transcripts. We identified seven key behavioral insights representing a range of factors that may contribute to delays in appropriate PPH management in these settings. Findings suggest providers' perceived low risk of PPH may influence their compliance with best practices, subconsciously or explicitly, and lead them to undervalue the importance of PPH prevention and monitoring measures. Providers lack clear feedback on specific components of their performance, which ultimately inhibits continuous improvement of compliance with best practices. Providers demonstrate great resourcefulness while operating in a challenging context with limited equipment, supplies, and support; however, overcoming these challenges remains their foremost concern. This response to chronic scarcity is cognitively taxing and may ultimately affect clinical decision-making. Our study reveals how perception of low risk of PPH, limited feedback on compliance with best practices and consequences of current practices, and a context of scarcity may negatively affect provider decision-making and clinical practices. Behaviorally informed interventions, designed for specific contexts that care providers operate in, can help improve quality of care and health outcomes for women in labor and childbirth.


The efficacy of a standardized questionnaire in facilitating personalized communication about problems encountered in cancer genetic counseling: design of a randomized controlled trial.
Individuals with a personal or family history of cancer, can opt for genetic counseling and DNA-testing. Approximately 25% of these individuals experience clinically relevant levels of psychosocial distress, depression and/or anxiety after counseling. These problems are frequently left undetected by genetic counselors. The aim of this study is to evaluate the efficacy of a cancer genetics-specific screening questionnaire for psychosocial problems, the 'Psychosocial Aspects of Hereditary Cancer (PAHC) questionnaire' together with the Distress Thermometer, in: (1) facilitating personalized counselor-counselee communication; (2) increasing counselors' awareness of their counselees' psychosocial problems; and (3) facilitating the management of psychosocial problems during and after genetic counseling. This multicenter, randomized controlled trial will include 264 individuals undergoing cancer genetic counseling in two family cancer clinics in the Netherlands. Participants will be randomized to either: (1) an intervention group that completes the PAHC questionnaire, the results of which are made available to the genetic counselor prior to the counseling session; or (2) a control group that completes the PAHC questionnaire, but without feedback being given to the genetic counselor. The genetic counseling sessions will be audiotaped for content analysis. Additionally, study participants will be asked to complete questionnaires at baseline, three weeks after the initial counseling session, and four months after a telephone follow-up counseling session. The genetic counselors will be asked to complete questionnaires at the start of and at completion of the study, as well as a checklist directly after each counseling session. The questionnaires/checklists of the study include items on communication during genetic counseling, counselor awareness of their clients' psychosocial problems, the (perceived) need for professional psychosocial support, cancer worries, general distress, specific psychosocial problems, satisfaction with care received, and experience using the PAHC questionnaire. This study will provide empirical evidence regarding the efficacy of a relatively brief psychosocial screening questionnaire in terms of facilitating personalized communication, increasing counselors' awareness, and optimizing management of psychosocial problems in the cancer genetic counseling setting. This study is registered at the Netherlands Trial Register (NTR3205) and ClinicalTrials.gov (NCT01562431).


Dominant influence of an HLA-B27 restricted CD8+ T cell response in mediating HCV clearance and evolution.
Virus-specific CD8+ T cell responses play an important role in the natural course of infection; however, the impact of certain CD8+ T cell responses in determining clinical outcome has not been fully defined. A well-defined cohort of women inoculated with HCV from a single source showed that HLA-B27 has a strong association with spontaneous clearance. The immunological basis for this association is unknown. However, the finding is especially significant because HLA-B27 has also been shown to have a protective role in HIV infection. We report the identification of an HLA-B27 restricted hepatitis C virus (HCV)-specific CD8+ T cell epitope that is recognized in the majority of recovered HLA-B27 positive women. In chronically HCV-infected individuals, analysis of the corresponding viral sequence showed a strong association between sequence variations within this epitope and expression of HLA-B27, indicating allele-specific selection pressure at the population level. Functional analysis in 3 chronically HCV-infected patients showed that the emerging variant viral epitopes represent escape mutations. In conclusion, our results suggest a dominant role of HLA-B27 in mediating spontaneous viral clearance as well as viral evolution in HCV infection and mechanistically link both associations to a dominant novel CD8+ T cell epitope. These results support the central role of virus-specific CD8+ T cells and the genetically determined restriction of the virus-specific T cell repertoire in HCV infection.


Effects of terminal nonhomology and homeology on double-strand-break-induced gene conversion tract directionality.
Double-strand breaks (DSBs) greatly enhance gene conversion in the yeast Saccharomyces cerevisiae. In prior plasmid x chromosome crosses, conversion tracts were often short ( < 53 bp) and usually extended in only one direction from a DSB in an HO recognition sequence inserted into ura3. To allow fine-structure analysis of short and unidirectional tracts, phenotypically silent markers were introduced at 3- and 6-bp intervals flanking the HO site. These markers, which created a 70-bp homeologous region (71% homology), greatly increased the proportion of bidirectional tracts. Among products with short or unidirectional tracts, 85% were highly directional, converting markers on only one side (the nearest marker being 6 bp from the HO site). A DSB in an HO site insertion creates terminal nonhomologies. The high degree of directionality is a likely consequence of the precise cleavage at homology/nonhomology borders in hybrid DNA by Rad1/10 endonuclease. In contrast, terminal homeology alone yielded mostly unidirectional tracts. Thus, nonhomology flanked by homeology yields primarily bidirectional tracts, but terminal homeology or nonhomology alone yields primarily unidirectional tracts. These results are inconsistent with uni- and bidirectional tracts arising from one- and two-ended invasion mechanisms, respectively, as reduced homology would be expected to favor one-ended events. Tract spectra with terminal homeology alone with similar in RAD1 and rad1 cells, indicating that the high proportion of bidirectional tracts seen with homeology flanking nonhomology is not a consequence of Rad1/10 cleavage at homology/homeology boundaries. Instead, tract directionality appears to reflect the influence of the degree of broken-end homology on mismatch repair.


Turning It Over to God: African American Assisted Living Residents' End-of-Life Preferences and Advance Care Planning.
Assisted living (AL), a popular long-term care setting for older Americans, increasingly is a site for end-of-life care. Although most residents prefer AL to be their final home, relatively little is known about end-of-life preferences and advance care planning, especially among African American residents. Our research addresses this knowledge gap. Informed by grounded theory, we present an analysis of qualitative data collected over 2 years in a 100-bed AL community catering to African American residents. Data consisted of field notes from participant observation conducted during 310 site visits and 818 observation hours, in-depth interviews with 25 residents, and a review of their AL records. Residents varied in their end-of-life preferences and advance care planning, but united in the belief that God was in control. We identified "Turning it over to God" as an explanatory framework for understanding how this group negotiated end-of-life preferences and advance care planning. Individual-level resident factors (e.g., age, pain, and function) and factors reflecting broader cultural and societal influences, including health literacy and care experiences, were influential. Contradictions arose from turning it over to God, including those between care preferences, planning, and anticipated or actual end-of-life outcomes.


Could Statin Use Be Associated with Reduced Recurrence Rates following Coiling in Ruptured Intracranial Aneurysms?
A number of studies have examined the role of matrix metalloproteinases in aneurysm healing following endovascular coiling. Because ruptured aneurysms are known to express higher levels of matrix metalloproteinases, we hypothesized that patients with subarachnoid hemorrhage who were on a statin at the time of coil embolization would have lower aneurysm recanalization and retreatment rates than patients not on statins. We performed a retrospective chart review of patients who underwent intrasaccular coil embolization of ruptured intracranial aneurysms of ≤10 mm with at least 6 months of imaging follow-up. Patients were separated into 2 groups: 1) those on an oral statin medication at the time of coiling, and 2) those who were not. Outcomes studied were aneurysm recurrence and aneurysm retreatment after endovascular coiling. Student t and χ(2) tests were used for statistical significance of differences between groups. One hundred thirty-two patients with 132 ruptured aneurysms were included in our study. Sixteen were on statins (12.1%) and 116 were not (87.9%). The recurrence rate was 6.3% in the statin group (1/16) and 36.2% in the nonstatin group (42/107) (P = .02). Unplanned retreatment rates were 6.3% (1/16) for the statin group and 25.9% (30/116) for the nonstatin group (P = .08). Statins were associated with a lower rate of aneurysm recurrence following endovascular coiling of small- and medium-sized ruptured aneurysms in this small retrospective study. Further studies are needed to confirm this finding to determine whether statins can be used to reduce recurrence rates in these aneurysms.


Contributions to the knowledge of amphibians and reptiles from Volta Grande do Xingu, northern Brazil.
The region of Volta Grande do Xingu River, in the state of Pará, presents several kinds of land use ranging from extensive cattle farming to agroforestry, and deforestation. Currently, the Belo Monte Hydroelectric Power Plant affects the region. We present a checklist of amphibians and reptiles of the region and discuss information regarding the spatial distribution of the assemblies based on results of Environmental Programmes conducted in the area. We listed 109 amphibian (Anura, Caudata, and Gymnophiona) and 150 reptile (Squamata, Testudines, and Crocodylia) species. The regional species richness is still considered underestimated, considering the taxonomic uncertainty, complexity and cryptic diversity of various species, as observed in other regions of the Amazon biome. Efforts for scientific collection and studies related to integrative taxonomy are needed to elucidate uncertainties and increase levels of knowledge of the local diversity.


Pain, functional disability, and their Association in Juvenile Fibromyalgia Compared to other pediatric rheumatic diseases.
Severe pain and impairments in functioning are commonly reported for youth with juvenile fibromyalgia. The prevalence and impact of pain in other diseases commonly managed in pediatric rheumatology comparatively have been rarely systematically studied. The objective of the current study was to determine the extent to which high levels of pain and functional limitations, and the strength of their association, are unique to youth with juvenile primary fibromyalgia syndrome/JPFS) relative to other pediatric rheumatic diseases. Using data from 7753 patients enrolled in the multinational Childhood Arthritis and Rheumatology Research Alliance (CARRA) Legacy Registry, we compared the levels and association of pain and functional limitations between youth with JPFS and those with other rheumatic diseases. Pain levels were rated highest among youth with JPFS (M = 6.4/10, SD = 2.4) and lowest for juvenile dermatomyositis (M = 1.7/10, SD = 2.2), with pain significantly higher in the JPFS group than any other pediatric rheumatic disease (effect sizes = .22 to 1.05). Ratings on measures of functioning and well-being also were significantly worse for patients with JPFS than patients with any other rheumatic disease (effect sizes = .62 to 1.06). The magnitude of association between pain intensity and functional disability, however, generally was higher in other rheumatic diseases than in JPFS. Pain was most strongly associated with functional limitations in juvenile dermatomyositis, juvenile idiopathic arthritis, and mixed connective tissue disease. JPFS is unique among conditions seen in pediatric rheumatology with regard to ratings of pain and disability. However, pain appears to be comparably or more highly associated with level of functional impairment in other pediatric rheumatic diseases. Pain in childhood rheumatic disease thus would benefit from increased prioritization for research and treatment.


A Cross-sectional Study of Gender-related Differences in Reporting Fatigue and Pain among Latino/A Migrant Farmworkers.
Objectives: Migrant farmworkers face many hardships in both their working and living environments including dangerous and demanding tasks, long hours, and inadequate rest. This study sought to explore gender differences in the reporting of fatigue and pain and to identify predictors of fatigue and pain among migrant farmworkers in Nebraska (n = 241). Methods: Bivariate tests were used to assess associations among study variables. Linear and generalized linear mixed effect models were used to assess gender as a predictor of fatigue and pain respectively while controlling for covariates. Results: Females reported significantly higher levels of fatigue (M score = 15.5, SD = 6.1 compared to M score = 12.8, SD = 4.3) than their male counterparts. Females were also more likely to report pain (56.9% of females compared to 36.3% of males). Being female, pain, hours of sleep, and job demands were significant predictors of fatigue. Fatigue and job-related injury were the only significant predictors of pain. Conclusions: There are gender-related disparities in the reporting of fatigue and pain among Latino/a migrant farmworkers. Extra precautions need to be taken to protect worker health and safety and reduce fatigue, particularly for female workers. Implications for employers, supervisors, and healthcare providers are discussed.


Effect of single and double strap backpacks on lung function.
Carrying heavy and moderate military loads in backpacks or as body armour compresses the chest, causing a change in lung function that is typical of a restrictive ventilatory impairment. It is not known if a lighter backpack load of only 6 kg, such as is typical of loads carried by students, will have a similar effect on lung function. There have been no studies examining whether backpacks of different strapping styles have an effect on lung function. Several designs of student backpack have recently been introduced to the market. One of the most popular is a single-strap backpack. This study examined Forced Vital Capacity (FVC), Forced Expiratory Volume in one second (FEV1), FEV1.FVC( - 1)% and Peak Expiratory Flow (PEF) in 13 participants (4 males, 9 females) wearing each of two 6 kg backpacks, one with two shoulder straps (a Double Strap Backpack (DSB)) and the other with a single strap (a Single Strap Backpack (SSB)) worn across the shoulder and chest. In comparison with the control of no pack (N), SSB significantly reduced FVC (by 3.94%, p = 0.006) but there were no significant differences in FEV1, FEV1. FVC( - 1)% and PEF. The DSB also significantly reduced FVC (by 1.97%, p = 0.034) but no significant differences were found in FEV1, FEV1. FVC( - 1)% and PEF measures. In comparison with DSB, the SSB was associated with a significantly lower FVC (by 2.05%, p = 0.049) and FEV1 (by 1.88%, p = 0.029) but there were no significant changes in FEV1. FVC( - 1)% and PEF. It is concluded that a backpack load of 6 kg could produce a mild restrictive type of ventilatory impairment in lung function. This effect was greater for a single cross-chest strap than for a more conventional double strap harness.


Droplet degeneration of the cornea in North Cameroon. Prevalence and clinical appearances.
The prevalence of droplet degeneration of the cornea in a defined population of 517 persons in north Cameroon was similar in males and females, but severe changes were commoner in elderly men. Most cases showed only mild changes of granularity and droplet formation in Bowman's zone, but they were sometimes widespread. More severe changes were seen in only nine patients. The clinical appearances are compared with those described from other parts of the world. In support of the aetiological role of direct sunlight, droplet degeneration was much more prevalent in the savanna than in the rain-forest in Cameroon. The condition ranges in severity from very mild to very severe, but difficulties in differential diagnosis, particularly in advanced cases, make it doubtful whether the same basic condition is being described in all cases. These doubts will be resolved only by properly conducted epidemiological studies in different parts of the world.


A three-dimensional underwater sound propagation model for offshore wind farm noise prediction.
A three-dimensional underwater sound propagation model with realistic ocean environmental conditions has been created for assessing the impacts of noise from offshore wind farm construction and operation. This model utilizes an existing accurate numerical solution scheme to solve the three-dimensional Helmholtz wave equation, and it is compared and validated with acoustic transmission data between 750 and 1250 Hz collected during the development of the Block Island Wind Farm (BIWF), Rhode Island. The variability of underwater sound propagation conditions has been investigated in the BIWF area on a temporal scale of months and a spatial scale of kilometers. This study suggests that future offshore wind farm developments can exploit the seasonal variability of underwater sound propagation for mitigating noise impact by scheduling wind farm construction during periods of high acoustic transmission loss. Discussions on other applications of soundscape prediction, planning, and management are provided.


Novel uses for statins in surgical patients.
Aside from their cholesterol-lowering effects statins are known to have a range of other 'pleiotropic' effects. We present an overview of the basic science behind these effects and then review clinical trials and the current role of statins relevant to modern surgical practice. A systematic review of the literature was performed using the keywords surgery and the MeSH term for statins. All clinical studies relating to statin use in surgical patients were evaluated. An overview of the literature on statin use and cardiac outcomes was performed. Statins are safe and have a wide range of pleiotropic effects relevant to surgical practice. Strongest evidence for their clinical use comes in primary cardiac risk reduction in many types of vascular surgery. There is a large body of evidence showing their benefit perioperatively in high-risk vascular and cardiac surgery but the picture is less clear for low-risk patients. Further studies are needed to evaluate exact dosage regimes and timing of administration. Novel uses of their anti-inflammatory properties in sepsis and vasomotor properties in subarachnoid haemorrhage are being further investigated by randomised trials.


Medical home quality and readmission risk for children hospitalized with asthma exacerbations.
The medical home likely has a positive effect on outpatient outcomes for children with asthma. However, no information is available regarding the impact of medical home quality on health care utilization after hospitalizations. We sought to explore the relationship between medical home quality and readmission risk in children hospitalized for asthma exacerbations. We enrolled 601 children, aged 1 to 16 years, hospitalized for an acute asthma exacerbation at a single pediatric facility that captures >85% of all asthma admissions in an 8-county area. Caregivers completed the Parent's Perception of Primary Care (P3C), a Likert-based, validated survey. The P3C yields a total score of medical home quality and 6 subscale scores assessing continuity, access, contextual knowledge, comprehensiveness, communication, and coordination. Asthma readmission events were prospectively collected via billing data. Hazards of readmission were calculated by using Cox proportional hazards adjusting for chronic asthma severity and key measures of socioeconomic status. Overall P3C score was not associated with readmission. Among the subscale comparisons, only children with lowest access had a statistically increased readmission risk compared with children with the best access. Subgroup analysis revealed that children with private insurance and good access had the lowest rates of readmission within a year compared with other combinations of insurance and access. Among measured aspects of medical home in a cohort of hospitalized children with asthma, having poor access to a medical home was the only measure associated with increased readmission. Improving physician access for children with asthma may lower hospital readmission.


Expression-state boundaries in the mating-type region of fission yeast.
A transcriptionally silent chromosomal domain is found in the mating-type region of fission yeast. Here we show that this domain is delimited by 2-kb inverted repeats, IR-L and IR-R. IR-L and IR-R prevent the expansion of transcription-permissive chromatin into the silenced region and that of silenced chromatin into the expressed region. Their insulator activity is partially orientation dependent. The silencing defects that follow deletion or inversion of IR-R are suppressed by high dosage of the chromodomain protein Swi6. Combining chromosomal deletions and Swi6 overexpression shows that IR-L and IR-R provide firm borders in a region where competition between silencing and transcriptional competence occurs. IR-R possesses autonomously replicating sequence (ARS) activity, leading to a model where replication factors, or replication itself, participate in boundary formation.


Pineapple bacilliform CO virus: Diversity, Detection, Distribution, and Transmission.
Members of the genus Badnavirus (family Caulimovirdae) have been identified in dicots and monocots worldwide. The genome of a pineapple badnavirus, designated Pineapple bacilliform CO virus-HI1 (PBCOV-HI1), and nine genomic variants (A through H) were isolated and sequenced from pineapple, Ananas comosus, in Hawaii. The 7,451-nucleotide genome of PBCOV-HI1 possesses three open reading frames (ORFs) encoding putative proteins of 20 (ORF1), 15 (ORF2), and 211 (ORF3) kDa. ORF3 encodes a polyprotein that includes a putative movement protein and viral aspartyl proteinase, reverse transcriptase, and RNase H regions. Three distinct groups of putative endogenous pineapple pararetroviral sequences and Metaviridae-like retrotransposons encoding long terminal repeat, reverse-transcriptase, RNase H, and integrase regions were also identified from the pineapple genome. Detection assays were developed to distinguish PBCOV-HI1 and genomic variants, putative endogenous pararetrovirus sequences, and Ananas Metaviridae sequences also identified in pineapple. PBCOV-HI1 incidences in two commercially grown pineapple hybrids, PRI 73-114 and PRI 73-50, was 34 to 68%. PBCOV-HI1 was transmitted by gray pineapple mealybugs, Dysmicoccus neobrevipes, to pineapple.


Paternity after bilateral cryptorchidism. A controlled study.
To compare paternity among men with former bilateral cryptorchidism (referred to as the bilateral group) with a group of men with former unilateral cryptorchidism (referred to as the unilateral group) and a control group. Epidemiologic survey of study cohort. Large urban pediatric hospital. Men with former bilateral and unilateral cryptorchidism who underwent orchiopexy between 1955 and 1971 at the Children's Hospital of Pittsburgh, Pittsburgh, Pa, and a group of control men have been surveyed by questionnaire concerning paternity and factors related to paternity. Paternity. Among the married men who had bilateral cryptorchidism, 50% had fathered children, compared with 76% in the control group and 74% in the unilateral group. Data were similar when the men who were cohabitating were included with the married men. When men who had married and had attempted paternity were evaluated, 62% of the men in the bilateral group had been able to father children compared with 94% of the control group and 89% of the men in the unilateral group. No relationship was noted between the age of orchiopexy or lifestyle factors and paternity. Paternity among all groups was related to female-related infertility factors and to the presence of varicoceles. Paternity was compromised after bilateral cryptorchidism when compared with men with former unilateral cryptorchidism and a control group. Among the bilateral group, infertility is about 3.5 times as frequent than the unilateral group and more than 6 times as frequent among the control group. No correlation was found between age of orchiopexy and paternity for either group.


The recall of information from working memory. Insights from behavioural and chronometric perspectives.
We describe and evaluate a recall reconstruction hypothesis for working memory (WM), according to which items can be recovered from multiple memory representations. Across four experiments, participants recalled memoranda that were either integrated with or independent of the sentence content. We found consistently longer pauses accompanying the correct recall of integrated compared with independent words, supporting the argument that sentence memory could scaffold the access of target items. Integrated words were also more likely to be recalled correctly, dependent on the details of the task. Experiment 1 investigated the chronometry of spoken recall for word span and reading span, with participants completing an unfinished sentence in the latter case. Experiments 2 and 3 confirm recall time differences without using word generation requirements, while Experiment 4 used an item and order response choice paradigm with nonspoken responses. Data emphasise the value of recall timing in constraining theories of WM functioning.


Total cholesterol/HDL-cholesterol ratio discordance with LDL-cholesterol and non-HDL-cholesterol and incidence of atherosclerotic cardiovascular disease in primary prevention: The ARIC study.
The total cholesterol (TC)/high-density lipoprotein (HDL) cholesterol ratio may carry additional information not available in more commonly used single cholesterol measures. Analysis of discordance between lipid parameters might help assess the impact of such additional information on the risk of atherosclerotic cardiovascular disease. We aimed to investigate the role of the TC/HDL-cholesterol ratio in determining atherosclerotic cardiovascular disease risk when discordant with low-density lipoprotein (LDL) cholesterol and non-HDL-cholesterol. We studied 14,403 Atherosclerosis Risk in Communities (ARIC) study participants who were free of atherosclerotic cardiovascular disease at baseline. TC/HDL-cholesterol discordance with LDL-cholesterol (estimated by the novel Martin/Hopkins method) and non-HDL-cholesterol was assessed at five visits and determined by being at or above the median for each lipid parameter. We constructed Cox proportional hazard models to estimate the risk for incident atherosclerotic cardiovascular disease events associated with each lipid concordance/discordance category using a time-varying approach. Mean age of participants was 54.1 years, 56% women and 25% black. There were 2634 atherosclerotic cardiovascular disease events over a median (interquartile range) follow-up of 24.2 (16.0-25.4) years. Among individuals with LDL-cholesterol and non-HDL-cholesterol less than the median, 26% and 21% had discordant TC/HDL-cholesterol at or above the median, respectively. These individuals had a 24% (hazard ratio (HR) 1.24, 95% confidence interval (CI) 1.09, 1.41) and 29% (HR 1.29, 95% CI 1.13, 1.46) greater risk of incident atherosclerotic cardiovascular disease, respectively, compared to those with TC/HDL-cholesterol less than the median after multivariable adjustment. In individuals with diabetes with LDL-cholesterol or non-HDL-cholesterol less than the median, discordant TC/HDL-cholesterol at or above the median was more prevalent at 48% and 38%, respectively. Clinically significant discordance exists between TC/HDL-cholesterol, available from the standard lipid profile, and the routinely used non-HDL-cholesterol and LDL-cholesterol. Such discordance may help inform atherosclerotic cardiovascular disease risk management, particularly in individuals with diabetes in whom discordance is more common.


mAbs: a business perspective.
The twenty two monoclonal antibodies (mAbs) currently marketed in the U.S. have captured almost half of the top-20 U.S. therapeutic biotechnology sales for 2007. Eight of these products have annual sales each of more than $1 B, were developed in the relatively short average period of six years, qualified for FDA programs designed to accelerate drug approval, and their cost has been reimbursed liberally by payers. With growth of the product class driven primarily by advancements in protein engineering and the low probability of generic threats, mAbs are now the largest class of biological therapies under development. The high cost of these drugs and the lack of generic competition conflict with a financially stressed health system, setting reimbursement by payers as the major limiting factor to growth. Advances in mAb engineering are likely to result in more effective mAb drugs and an expansion of the therapeutic indications covered by the class. The parallel development of biomarkers for identifying the patient subpopulations most likely to respond to treatment may lead to a more cost-effective use of these drugs. To achieve the success of the current top-tier mAbs, companies developing new mAb products must adapt to a significantly more challenging commercial environment.


Defective development of the embryonic and extraembryonic circulatory systems in vascular cell adhesion molecule (VCAM-1) deficient mice.
VCAM-1 is a cytokine-inducible cell surface protein capable of mediating adhesion to leukocytes expressing alpha 4 integrins. Mice deficient in VCAM-1 expression were produced by targeted homologous recombination in ES cells. VCAM-1-deficient embryos were not viable and exhibited either of two distinct phenotypes. Approximately half of the embryos died before embryonic day 11.5 and exhibited a severe defect in placental development in which the allantois failed to fuse with the chorion. The remaining VCAM-1-deficient embryos survived to embryonic day 11.5-12.5 and displayed several abnormalities in their developing hearts including a reduction of the compact layer of the ventricular myocardium and intraventricular septum. The hearts also contained significant amounts of blood in the pericardial space and lacked an epicardium. alpha 4 and VCAM-1 were found to be expressed in wild-type embryos in a reciprocal fashion in the chorion and allantois and in the epicardium and the underlying myocardium, although VCAM-1 was expressed in the intraventricular septum in the absence of adjacent alpha 4-expressing cells. These data suggest important roles for VCAM-1 and alpha 4 in the development of the placenta and the heart.


Effect of Sahaja yoga meditation on auditory evoked potentials (AEP) and visual contrast sensitivity (VCS) in epileptics.
The effect of Sahaja yoga meditation on 32 patients with primary idiopathic epilepsy on regular and maintained antiepileptic medication was studied. The patients were randomly divided into 3 groups: group I practiced Sahaja Yoga meditation twice daily for 6 months under proper guidance; group II practiced postural exercises mimicking the meditation for the same duration; and group III was the control group. Visual Contrast Sensitivity (VCS), Auditory Evoked Potentials (AEP), Brainstem Auditory Evoked Potentials (BAEP), and Mid Latency Responses (MLR) were recorded initially (0 month) and at 3 and 6 months for each group. There was a significant improvement in VCS following meditation practice in group I participants. Na, the first prominent negative peak of MLR and Pa, the positive peak following Na did not register changes in latency. The Na-Pa amplitude of MLR also showed a significant increase. There were no significant changes in the absolute and interpeak latencies of BAEP. The reduced level of stress following meditation practice may make patients more responsive to specific stimuli. Sahaja Yoga meditation appears to bring about changes in some of the electrophysiological responses studied in epileptic patients.


Influence of SYSADOA group chemicals on progression of human knee joint osteoarthritis: new objective evaluation method - measuring of rheological properties in vivo.
This study seeks to demonstrate the influence of pharmacological substances from the SYSADOA group on the progression of osteoarthritis in the human knee. The quantification methods were direct measurement of the rheological properties of the knee joints in vivo and standard WOMAC index questionnaires. The drugs were administered orally to 34 probands with second degree gonarthrosis for 13 weeks. The untreated control group consisted of 10 probands. The rheological properties of the joints were determined by a biorheometer, and subjective assessment of the knees by patients (WOMAC) before and after medication, and for a further 13 weeks. Changes in the calculated parameters over time were compared. During the audited perioda slight deterioration in all of the parameters was observed in the untreated group. The treated group, however, improved in all the parameters and some indicators showed statistically significant differences. The positive effects of the SYSADOA persisted for 3 months after the end of treatments. Partial correlation was found between the results of the WOMAC questionnaire and the rheological measurements. This study shows the positive effects of the preparation on arthritic changes in the knee joint, but due to the large variance of the collected data, this conclusion is on the borderline of statistical significance. The method of measuring the rheological properties of the joints is suitable for evaluating the progression of OA.


Assessment of proprioceptive exercises in the treatment of rotator cuff disorders in nursing professionals: a randomized controlled clinical trial.
Shoulder pain in nursing professionals may lead to limitations in occupational and daily activities and consequently interfere with quality of life. To compare the effects of two physical therapy programs which differed in the proprioceptive exercises used on the nursing professionals with rotator cuff disorder, according to quality of life, work satisfaction indicators, and pain intensity. This study was an experimental, randomized, prospective, comparative trial with quantitative data analysis. The data sampling was carried out between the months of June 2010 and July 2011 by means of a questionnaire containing socio-demographic and professional information, the Western Ontario Rotator Cuff Index (WORC), the Occupational Stress Indicator (OSI), and the Visual Numeric Scale (VNS). Based on randomization, subjects were divided into two groups. Group 1 (control) was submitted to stretching and strengthening exercises and cryotherapy. Group 2 (experimental) was treated with the same protocol as the control group, with the addition of proprioception exercises. The data was analyzed by means of the Statistical Package for the Social Science version 16.0 for Windows. After physical therapy intervention, significant reduction in pain levels occurred in both groups, with a significant improvement in quality of life for Group 2. No changes were observed in the work satisfaction indicators after the two types of physical therapy interventions. The proprioceptive exercises were important in the treatment of musculoskeletal disorders, however the results did not allow us to determine which treatment was the most effective as there was no significant difference between groups.


Physical Activity Patterns Among Older Adults With and Without Knee Osteoarthritis in Six European Countries.
To investigate patterns of physical activity in older adults with knee osteoarthritis (OA) compared to older adults without knee OA across 6 European countries. We expect country-specific differences in the physical activity levels between persons with knee OA compared to persons without knee OA. A varying degree of physical activity levels across countries would express a facilitating or impeding influence of the social, environmental, and other contextual factors on a physically active lifestyle. Baseline cross-sectional data from the European Project on Osteoarthritis were analyzed. In total, 2,551 participants from 6 European countries (Germany, Italy, The Netherlands, Spain, Sweden, and the UK) were included. Participants with knee OA were less likely to follow physical activity recommendations and had poorer overall physical activity profiles than those without knee OA (mean 62.9 versus 81.5 minutes/day, respectively; P = 0.015). The magnitude of this difference varied across countries. Detailed analysis showed that low physical activity levels in persons with knee OA could be attributed to less everyday walking time (odds ratio 1.31, 95% confidence interval 1.07-1.62). This study highlighted the fact that having knee OA is associated with a varying degree of physical activity patterns in different countries. This national variation implies that low levels of physical activity among persons with knee OA cannot be explained exclusively by individual or disease-specific factors, but that social, environmental, and other contextual factors should also be taken into account.


Relationship of oxidative stress to visceral adiposity in youth and role played by vitamin D.
Visceral adipose tissue (VAT) accumulation is a major cardiometabolic risk factor, associated with increased inflammation. Oxidative stress (OS) is also associated with inflammation and cardiometabolic issues, yet mainly through general obesity. Both OS and obesity were linked to vitamin D deficiency. To investigate whether OS increase is associated with VAT accumulation in youth, and whether in the presence of VAT accumulation, a higher vitamin D status is associated with lower OS. One hundred and fifty-eight youth with overweight/obesity, 7 to 17 years old, were recruited (Pediatric Clinic, Luxembourg). We assessed visceral and subcutaneous abdominal adipose tissues by magnetic resonance imaging, OS by DNA/RNA oxidative damage with ELISA and vitamin D by high-performance liquid chromatography. VAT was the body fat compartment the most strongly associated with OS (RPearson : 0.298; P < 10-4 ). The general linear (GLM) models assessing the relationship between OS, VAT and vitamin D concentrations showed that "Log10 OS = (0.003 × VAT) + 3.911 (R2adjusted : 0.083; P-value < 10-4 )"; "Log10 OS = (0.003 × VAT) - (0.156 × log10 vitamin D) + 4.110 (R2adjusted : 0.101; P-value < 10-4 )". After back-transformation of the log-values into normal values, the GLM showed that, for a person with an average value of VAT (40.7 cm2 ), a 10 cm2 increase in VAT would increase OS by approx. 771.833 pg/mL, after age, gender, Tanner stage and physical activity adjustment. An approximate increase of 9 ng/mL of vitamin D would counterbalance this negative effect of increased VAT. Dietary strategies improving vitamin D status should be investigated to tackle VAT and OS increase.


Monolithic molecularly imprinted polymeric capillary columns for isolation of aflatoxins.
Monolithic molecularly imprinted polymers extraction columns have been prepared in fused-silica capillaries by UV or thermal polymerization in a two-step process. First, a poly-(trimethylolpropane trimethacrylate) (polyTRIM) core monolith was synthesized either by UV or thermal polymerization. Then it was grafted with the mixture of methacrylic acid (MAA) as a functional monomer, ethylene dimethacrylate (EDMA) as a cross-linking agent, 5,7-dimethoxycoumarin (DMC) as an aflatoxin-mimicking template, toluene as a porogen solvent and 2,2-azobis-(2-methylpropionitrile) (AIBN) as an initiator of the polymerization reaction. Different thermal condition of the photografting and different concentrations of the grafting mixture were tested during polymerization. The extraction capillary columns were evaluated in the terms of their hydrodynamic and chromatographic properties. Retention coefficients for aflatoxin B1 and DMC were used for assessment of the selectivity and imprinting factor. The obtained results indicate that the temperature of photografting and concentration of the grafting mixture are key parameters that determine the quality of the prepared MIPs. From the MIP columns characterized by the highest permeability the column of the highest imprinting factor was applied for isolation of aflatoxins B1, B2, G1 and G2 from the model aqueous sample followed by on-line chromatographic separation. The process was performed using a micro-MISPE-microLC-LIF system of a novel design, which allowed for detection of the eluates from the sample preparation part as well as from the chromatographic separation.


Comparative cytological responses of lung epithelial and pleural mesothelial cells following in vitro exposure to nanoscale SiO2.
Due to unique surface chemistries and the ability to easily functionalize their surface, amorphous silica nanoparticles are being assimilated into medicinal and consumer products at an increasing rate. Subsequently, there is an emergent need to understand the interactions of these particulates with biological systems in an attempt to mitigate toxicity. The identification of susceptible or resistant cell types of the pulmonary system remains a critical step in the development of toxicity assessments for nanoparticle-based platforms. Specific to this study, the cellular responses of A549 lung epithelial and MeT-5A pleural mesothelial cell lines as a means of detecting nanoparticle-induced oxidative stress were examined. Basal expression and cellular antioxidant activity, including SOD, CAT, and GSH, were examined prior to H(2)O(2) and ~30 nm SiO(2) (0.01-100mg/L) exposures. Dose-response observations were made regarding oxidant production, cytotoxicity, GSH depletion and NRF2 transcription factor activation. Results indicated that, while both cell types exhibited susceptibility to H(2)O(2) and SiO(2)-induced oxidative stress and damage, the A549 cell line was relatively more resilient.


Femoral lengthening over a humeral intramedullary nail in preadolescent children.
Femoral lengthening over an intramedullary nail has been described in adults. A technique of femoral lengthening over a humeral intramedullary nail in children is described, and the results and complications are presented. Nine preadolescent patients (average age, nine years and ten months) with femoral length discrepancy were treated with femoral lengthening over a humeral intramedullary nail. After nail insertion, a monolateral external fixator was placed with half-pins either anterior or posterior to the intramedullary nail, and lengthening was performed through a proximal osteotomy. The femora were lengthened a mean of 6.1 cm (range, 5.0 to 8.0 cm), 19.5% (range, 15.9% to 26.2%) of the preoperative femoral length. Patients had a mean lengthening index of 12.2 days/cm of length (range, 9.5 to 16.9 days/cm of length). Five complications including osteomyelitis, failure of the distal interlocking site, and femoral fracture at the distal end of the nail occurred in four patients; four of the complications led to surgical intervention. No case of proximal femoral valgus secondary to nailing through the greater trochanter had developed by the time of final follow-up. All patients were followed for a minimum of two years postoperatively, with a mean of 128 weeks (range, 111 to 161 weeks). The technique is effective but has a high rate of complications, including osteomyelitis, which developed in two of the nine patients. No avascular necrosis or proximal femoral valgus was noted.


Moral consequences of becoming unemployed.
We test the conjecture that becoming unemployed erodes the extent to which a person acknowledges earned entitlement. We use behavioral experiments to generate incentive-compatible measures of individuals' tendencies to acknowledge earned entitlement and incorporate these experiments in a two-stage study. In the first stage, participants' acknowledgment of earned entitlement was measured by engaging them in the behavioral experiments, and their individual employment status and other relevant socioeconomic characteristics were recorded. In the second stage, a year later, the process was repeated using the same instruments. The combination of the experimentally generated data and the longitudinal design allows us to investigate our conjecture using a difference-in-difference approach, while ruling out the pure self-interest confound. We report evidence consistent with a large, negative effect of becoming unemployed on the acknowledgment of earned entitlement.


SGT1 is essential for Nod1 activation.
The Nod-like receptor family in man contains proteins that recognize invasive bacteria. Nod1, a member of this family, is activated by specific peptidoglycan-derived muropeptides that contain meso-diaminopimelic acid. Plants contain a large family of proteins known as resistance (R) proteins that have common structural features with the Nod-like receptors and are essential for protection against a variety of plant pathogens. Extensive genetic studies have shown that the R protein function is determined by multiple proteins including SGT1, Rar1, and HSP90. Here we show that SGT1 positively regulates Nod1 activation. Depletion of SGT1 with siRNA did not affect stability of Nod1 protein or of downstream signaling molecules but did prevent multiple cellular responses associated with Nod1 activation. In contrast, depletion of the mammalian orthologue of Rar1, Chp1, had no effect on Nod1-dependent cellular activation. Finally, depletion of HSP90 or addition of a pharmacologic inhibitor of HSP90 resulted in loss of Nod1 protein. Thus, we show common regulatory pathways in plant R protein and human Nod1-dependent pathways and provide the basis for understanding the Nod1 pathway.


Topological insulator metamaterials with tunable negative refractive index in the optical region.
A blueshift tunable metamaterial (MM) exhibiting a double-negative refractive index based on a topological insulator (bismuth selenide, Bi2Se3) has been demonstrated in the near-infrared (NIR) spectral region. The potential of Bi2Se3 as a dielectric interlayer of the multilayer MM is explored. The optical response of elliptical nanohole arrays penetrating through Au/Bi2Se3/Au films is numerically investigated using the finite difference time domain (FDTD) method. The blueshift tuning range of the MM is as high as 370 nm (from 2,140 to 1,770 nm) after switching the Bi2Se3 between its trigonal and orthorhombic states.


Disruption and sequence identification of 2,000 genes in mouse embryonic stem cells.
The dramatic increase in sequence information in the form of expressed sequence tags (ESTs) and genomic sequence has created a 'gene function gap' with the identification of new genes far outpacing the rate at which their function can be identified. The ability to create mutations in embryonic stem (ES) cells on a large scale by tagged random mutagenesis provides a powerful approach for determining gene function in a mammalian system; this approach is well established in lower organisms. Here we describe a high-throughput mutagenesis method based on gene trapping that allows the automated identification of sequence tags from the mutated genes. This method traps and mutates genes regardless of their expression status in ES cells. To facilitate the study of gene function on a large scale, we are using these techniques to create a library of ES cells called Omnibank, from which sequence-tagged mutations in 2,000 genes are described.


An efficient algorithm for Cholesky decomposition of electron repulsion integrals.
Approximating the electron repulsion integrals using inner projections is a well-established approach to reduce the computational demands of electronic structure calculations. Here, we present a two-step Cholesky decomposition algorithm where only the elements of the Cholesky basis (the pivots) are determined in the pivoting procedure. This allows for improved screening, significantly reducing memory usage and computational cost. After the pivots have been determined, the Cholesky vectors are constructed using the inner projection formulation. We also propose a partitioned decomposition approach where the Cholesky basis is chosen from a reduced set generated by decomposing diagonal blocks of the matrix. The algorithm extends the application range of the methodology and is well suited for multilevel methods. We apply the algorithm to systems with up to 80 000 atomic orbitals. The accuracy of the integral approximations is demonstrated for a formaldehyde-water system using a new Cholesky-based CCSD implementation.


Operation Everest. II: Nutrition and body composition.
Progressive body weight loss occurs during high mountain expeditions, but whether it is due to hypoxia, inadequate diet, malabsorption, or the multiple stresses of the harsh environment is unknown. To determine whether hypoxia due to decompression causes weight loss, six men, provided with a palatable ad libitum diet, were studied during progressive decompression to 240 Torr over 40 days in a hypobaric chamber where hypoxia was the major environmental variable. Caloric intake decreased 43.0% from 3,136 to 1,789 kcal/day (P less than 0.001). The percent carbohydrate in the diet decreased from 62.1 to 53.2% (P less than 0.001). Over the 40 days of the study the subjects lost 7.4 +/- 2.2 (SD) kg and 1.6% (2.5 kg) of the total body weight as fat. Computerized tomographic scans indicated that most of the weight loss was derived from fat-free weight. The data indicated that prolonged exposure to the increasing hypoxia was associated with a reduction in carbohydrate preference and body weight despite access to ample varieties and quantities of food. This study suggested that hypoxia can be sufficient cause for the weight loss and decreased food consumption reported by mountain expeditions at high altitude.


[Social impact of abusive alcohol consumption in Spain: consumption, cost and policies].
Although it has declined in recent decades, alcohol consumption in Spain is still high compared with other European countries. The consumption pattern shows a converging trend with Europe, with a decrease in consumption of wine and an increase in the consumption of beer. Likewise, mortality related to alcohol consumption has also declined in the last twenty years, but remains a major cause of death. The direct healthcare costs and indirect costs of diseases totally and partially attributable to alcohol consumption in 2007 was 2669.74 million. The effective tax regime in Spain gravel alcohol very little, so a substantial increase, in line with some European countries, could be an option to be considered for accelerating the reduction of the burden of morbidity and mortality associated with alcohol consumption.


Long-term maintenance therapy for post-cardiac transplant monoclonal lymphoproliferative disorder: caveat mammalian target of rapamycin.
A 53-year-old Caucasian male suffering from idiopathic dilated cardiomyopathy underwent cardiac transplantation. Fifty-seven days following transplant, he developed posttransplant lymphoproliferative disorder (PTLD), which was Epstein-Barr virus positive. The initial episode of PTLD was treated with a dose reduction in cyclosporine (CsA) and a 4-week course of rituximab. Subsequent biopsies showed resolution of PTLD. One year posttreatment, his evaluation revealed severe cardiac allograft vasculopathy (CAV). The patient was switched to sirolimus-based immunosuppression regimen with gradual up-titration of sirolimus in combination with complete withdrawal of previously administered Calcineurin-based immunosuppression approach. The switchover was carried out over a 6-week period. In the following 3 years, there was CAV regression as well as PTLD remission, without any significant episode of rejection. Despite frequent relapses with this form of PTLD, the patient remains in remission, 8 years posttransplantation. In summary, sirolimus has been demonstrated to attenuate the progression of CAV, and this case report illustrates that regression of CAV is possible. In addition to preventing rejection, mammalian target of rapamycin inhibitors directly suppress signaling pathways leading to PTLD and may be effective monotherapy for preventing rejection and suppressing PTLD.


Bacterial communities on food court tables and cleaning equipment in a shopping mall.
The food court at a shopping mall is a potential transfer point for pathogenic microbes, but to date, this environment has not been the subject of detailed molecular microbiological study. We used a combination of culture-based and culture-independent approaches to investigate the types and numbers of bacteria present on food court tables, and on a food court cleaning cloth. Bacteria were found at 10²-10⁵ c.f.u./m² on food court tables and 10¹⁰ c.f.u./m² on the cleaning cloth. Tag-pyrosequencing of amplified 16S rRNA genes revealed that the dominant bacterial types on the cleaning cloth were genera known to include pathogenic species (Stenotrophomonas, Aeromonas), and that these genera were also evident at lower levels on table surfaces, suggesting possible cross-contamination. The evidence suggests a public health threat is posed by bacteria in the food court, and that this may be due to cross-contamination between cleaning equipment and table surfaces.


Indoor localisation through object detection within multiple environments utilising a single wearable camera.
The recent growth in the wearable sensor market has stimulated new opportunities within the domain of Ambient Assisted Living, providing unique methods of collecting occupant information. This approach leverages contemporary wearable technology, Google Glass, to facilitate a unique first-person view of the occupants immediate environment. Machine vision techniques are employed to determine an occupant's location via environmental object detection. This method provides additional secondary benefits such as first person tracking within the environment and lack of required sensor interaction to determine occupant location. Object recognition is performed using the Oriented Features from Accelerated Segment Test and Rotated Binary Robust Independent Elementary Features algorithm with a K-Nearest Neighbour matcher to match the saved key-points of the objects to the scene. To validate the approach, an experimental set-up consisting of three ADL routines, each containing at least ten activities, ranging from drinking water to making a meal were considered. Ground truth was obtained from manually annotated video data and the approach was previously benchmarked against a common method of indoor localisation that employs dense sensor placement in order to validate the approach resulting in a recall, precision, and F-measure of 0.82, 0.96, and 0.88 respectively. This paper will go on to assess to the viability of applying the solution to differing environments, both in terms of performance and along with a qualitative analysis on the practical aspects of installing such a system within differing environments.


Can Photoplethysmography Replace Arterial Blood Pressure in the Assessment of Blood Pressure?
Arterial Blood Pressure (ABP) and photoplethysmography (PPG) are both useful techniques to monitor cardiovascular status. Though ABP monitoring is more widely employed, this procedure of signal acquisition whether done invasively or non-invasively may cause inconvenience and discomfort to the patients. PPG, however, is simple, noninvasive, and can be used for continuous measurement. This paper focuses on analyzing the similarities in time and frequency domains between ABP and PPG signals for normotensive, prehypertensive and hypertensive subjects and the feasibility of the classification of subjects considering the results of the analysis performed. From a database with 120 records of ABP and PPG, each 120 s in length, the records where separated into epochs taking into account 10 heartbeats, and the following statistical measures were performed: Correlation (r), Coherence (COH), Partial Coherence (pCOH), Partial Directed Coherence (PDC), Directed Transfer Function (DTF), Full Frequency Directed Transfer Function (ffDTF) and Direct Directed Transfer Function (dDTF). The correlation coefficient was r > 0.9 on average for all groups, indicating a strong morphology similarity. For COH and pCOH, coherence (linear correlation in frequency domain) was found with significance (p < 0.01) in differentiating between normotensive and hypertensive subjects using PPG signals. For the dataset at hand, only two synchrony measures are able to convincingly distinguish hypertensive subjects from normotensive control subjects, i.e., ffDTF and dDTF. From PDC, DTF, ffDTF, and dDTF, a consistent, a strong significant causality from ABP→PPG was found. When all synchrony measures were combined, an 87.5 % accuracy was achieved to detect hypertension using a Neural Network classifier, suggesting that PPG holds most informative features that exist in ABP.


Access to dihydropyridinones and spirooxindoles: application of N-heterocyclic carbene-catalyzed [3+3] annulation of enals and oxindole-derived enals with 2-aminoacrylates.
A strategy for the NHC-catalyzed synthesis of dihydropyridinones and spirooxindoles has been developed via [3+3] annulation reactions of enals or isatin-derived enals with 2-aminoacrylates under oxidative conditions. In this efficient strategy, the 2-aminoacrylates served as nucleophiles. Modifying the standard base switched the carbon-carbon double bond formation from 5,6-positions to 3,4-positions to generate 5,6-dihydropyridinones and 3,4-dihydropyridinones, respectively. Meanwhile, a diverse set of spirooxindole derivatives were also synthesized in good to excellent yields.


In need of constraint: Understanding the role of the cingulate cortex in the impulsive mind.
Impulsive behavior often occurs without forethought and can be driven by strong emotions or sudden impulses, leading to problems in cognition and behavior across a wide range of situations. Although neuroimaging studies have explored the neurocognitive indicators of impulsivity, the large-scale functional networks that contribute to different aspects of impulsive cognition remain unclear. In particular, we lack a coherent account of why impulsivity is associated with such a broad range of different psychological features. Here, we use resting state functional connectivity, acquired in two independent samples, to investigate the neural substrates underlying different aspects of self-reported impulsivity. Based on the involvement of the anterior cingulate cortex (ACC) in cognitive but also affective processes, five seed regions were placed along the caudal to rostral gradient of the ACC. We found that positive urgency was related to functional connectivity between subgenual ACC and bilateral parietal regions such as retrosplenial cortex potentially highlighting this connection as being important in the modulation of the non-prospective, hastiness - related aspects of impulsivity. Further, two impulsivity dimensions were associated with significant alterations in functional connectivity of the supragenual ACC: (i) lack of perseverance was positively correlated to connectivity with the bilateral dorsolateral prefrontal cortex and right inferior frontal gyrus and (ii) lack of premeditation was inversely associated with functional connectivity with clusters within bilateral occipital cortex. Further analysis revealed that these connectivity patterns overlapped with bilateral dorsolateral prefrontal and bilateral occipital regions of the multiple demand network, a large-scale neural system implicated in the general control of thought and action. Together these results demonstrate that different forms of impulsivity have different neural correlates, which are linked to the functional connectivity of a region of anterior cingulate cortex. This suggests that poor perseveration and premeditation might be linked to dysfunctions in how the rostral zone of the ACC interacts with the multiple demand network that allows cognition to proceed in a controlled way.


The Wand vs. traditional injection: a comparison of pain related behaviors.
The purpose of this study was to evaluate the efficacy of a computerized anesthesia delivery system (e.g., Wand) compared to a traditional anesthesia administration, with respect to reducing disruptive pain related behavior during injections. Subjects consisted of 62 patients between the ages of 5 and 13 requiring local anesthesia for dental restorations in the maxilla. Patients were randomly assigned to either the Wand or the traditional anesthetic delivery system. A palatal approach to the anterior and middle superior alveolar nerves and the anterior superior alveolar nerve was used with the Wand injections. Buccal infiltration and palatal injections were used for the traditional method. Pain behavior was observed and coded. Pain ratings were obtained. Subjects also rated their satisfaction with treatment. Results of chi-square tests found that the Wand injections produced significantly fewer patients who exhibited disruptive behavior during the initial 15 seconds of an injection when compared with those who received a traditional palatal injection. Wand patients were significantly less likely to cry, to exhibit disruptive body movements, and to require physical restraint. In contrast, there were no significant differences in disruptive behavior when comparing the Wand with the traditional buccal injection. Pain ratings showed no statistical difference between the Wand and the traditional injections. Wand injections can deliver proper anesthesia, utilizing one palatal injection site, while significantly reducing the likelihood of disruptive behaviors during the initial moments of an injection.