Computing the viscosity of supercooled liquids.
We describe an atomistic method for computing the viscosity of highly viscous liquids based on activated state kinetics. A basin-filling algorithm allowing the system to climb out of deep energy minima through a series of activation and relaxation is proposed and first benchmarked on the problem of adatom diffusion on a metal surface. It is then used to generate transition state pathway trajectories in the potential energy landscape of a binary Lennard-Jones system. Analysis of a sampled trajectory shows the system moves from one deep minimum to another by a process that involves high activation energy and the crossing of many local minima and saddle points. To use the trajectory data to compute the viscosity we derive a Markov Network model within the Green-Kubo formalism and show that it is capable of producing the temperature dependence in the low-viscosity regime described by molecular dynamics simulation, and in the high-viscosity regime (10(2)-10(12) Pa s) shown by experiments on fragile glass-forming liquids. We also derive a mean-field-like description involving a coarse-grained temperature-dependent activation barrier, and show it can account qualitatively for the fragile behavior. From the standpoint of molecular studies of transport phenomena this work provides access to long relaxation time processes beyond the reach of current molecular dynamics capabilities. In a companion paper we report a similar study of silica, a representative strong liquid. A comparison of the two systems gives insight into the fundamental difference between strong and fragile temperature variations.


Influence of particle size on regional lung deposition--what evidence is there?
The understanding of deposition of particles in the respiratory tract is of great value to risk assessment of inhalation toxicology and to improve efficiency in drug delivery of inhalation therapies. There are three main basic mechanisms of particle deposition based primarily on particle size: inertial impaction, sedimentation and diffusion. The regional deposition in the lungs can be evaluated in regards to the aerodynamic particle size, in which particle density plays a significant role. In this review paper, we first introduce the available imaging techniques to confirm regional deposition of particles in the human respiratory tract, such as planar scintigraphy, single photon emission computed tomography (SPECT) and positron emission tomography (PET). These technologies have widely advanced and consequently benefited the understanding of deposition pattern, although there is a lack of lung dosimetry techniques to evaluate the deposition of nanoparticles. Subsequently, we present a comprehensive review summarizing the evidence available in the literature that confirms the deposition of smaller particles in the smaller airways as opposed to the larger airways.


Interfering Plasmons in Coupled Nanoresonators to Boost Light Localization and SERS.
Plasmonic self-assembled nanocavities are ideal platforms for extreme light localization as they deliver mode volumes of <50 nm3. Here we show that high-order plasmonic modes within additional micrometer-scale resonators surrounding each nanocavity can boost light localization to intensity enhancements >105. Plasmon interference in these hybrid microresonator nanocavities produces surface-enhanced Raman scattering (SERS) signals many-fold larger than in the bare plasmonic constructs. These now allow remote access to molecules inside the ultrathin gaps, avoiding direct irradiation and thus preventing molecular damage. Combining subnanometer gaps with micrometer-scale resonators places a high computational demand on simulations, so a generalized boundary element method (BEM) solver is developed which requires 100-fold less computational resources to characterize these systems. Our results on extreme near-field enhancement open new potential for single-molecule photonic circuits, mid-infrared detectors, and remote spectroscopy.


MiR-9-5p could promote angiogenesis and radiosensitivity in cervical cancer by targeting SOCS5.
The aim of this study was to investigate the molecular mechanism of miRNA-9-5p in cervical cancer. The expression level of microRNA-9-5p (miR-9-5p) in cervical cancer (CC) tissues and cell lines was examined by quantitative Real Time-Polymerase Chain Reaction. Cells were transfected with Lipofectamine 3000. Cell proliferation was measured by Cell Counting Kit-8 (CCK-8). Invasion assays were performed in 24-well transwell chambers system with 8 μm pores. Cell invasion was evaluated by transwell assay. Western blot was used to detect the changes of epithelial-mesenchymal transition (EMT) and SOCS5. The effects of miR-9-5p on tubule formation were examined under different doses of γ radiation. Immunohistochemistry assay was used to analyze the protein expression of SOCS5. Fluorescence microscopy analysis was used to measure autophagosomes after cells treated with γ irradiation. From the Cancer Genome Atlas (TCGA) database, the expression of miR-9-5p was significantly higher in cervical cancer patients than in the negative ones, and it was verified in 22 paired of lymph node-positive patient tissues and negative. The overexpression of miR-9-5p promoted proliferation and invasion of cervical cancer cells in vitro and primary tumor growth in vivo. MiR-9-5p reduced the tubule generation after the radiation dose of 4Gy. Besides, we identified SOCS5 as the target of miR-9-5p, and the overexpression of SOCS5 could inhibit miR-9-5p mimics from promoting tubule formation. MiR-9-5p could promote proliferation and invasion of CC cells in vitro and in vivo. MiR-9-5p could affect angiogenesis and radiosensitivity of CC cells by targeting SOCS5.


Biological and Clinical Implications of the Vascular Endothelial Growth Factor Coreceptor Neuropilin-1 in Human Immunodeficiency Virus.
Plasma vascular endothelial growth factor (VEGF) coreceptor neuropilin-1 (NRP-1) had the largest association with coronary plaque in the Randomized Trial to Prevent Vascular Events in HIV (REPRIEVE) proteomics analysis. With little known about NRP-1 in people with human immunodeficiency virus (PWH), we explored its relation to other proteins in REPRIEVE and validated our findings through a Centers for AIDS Research Network of Integrated Clinical Systems (CNICS) case-cohort study by assessing its relation to host factors and incident cardiovascular disease and cancer. Within REPRIEVE, NRP-1 was associated with proteins involved in angiogenesis, signal transduction, immunoregulation, and cell migration/adhesion. Within CNICS, NRP-1 was associated with key host factors, including older age and male sex. NRP-1 was associated with an increased hazard of multiple cancers but a decreased prostate cancer risk. Finally, NRP-1 was most strongly associated with mortality and type 2 myocardial infarction. These data suggest that NRP-1 is part of a clinically relevant immunoregulatory pathway related to multiple comorbidities in PWH. Clinical Trials Registration. NCT02344290.


Choice of anesthesia in molybdenum cofactor deficiency: A case report.
Molybdenum cofactor (MC) deficiency is defined as a progressive neurodegenerative and neurometabolic disease, characterized by convulsions, severe mental and motor retardation resistant to the treatment. Patients with MC deficiency usually need at least sedation for even minor interventions such as dental examination or treatment. Sedation or general anesthesia for these patients may be complicated due to accompanying disorders. However, we were unable to find any reports on anesthetic management of patients with MC deficiency in the literature. In this article, we intend to share our experience of a patient with MC deficiency, who had undergone dental treatment under deep sedation.


Towards an integral conceptual model of frailty.
Most conceptual and operational definitions of frailty place heavy emphasis on the physical problems encountered by older people. The accompanying models are based largely on a medical model. An integral approach is almost never adopted. This study aims to develop both an integral operational definition of frailty and an integral conceptual model of frailty. In order to achieve these aims, a thorough literature search was performed on components of operational definitions and models of frailty. In addition, experts (N=17) were consulted during two expert meetings. There was consensus among the experts on the inclusion of the following components in the operational definition of frailty: strength, balance, nutrition, endurance, mobility, physical activity and cognition. Some respondents indicated that they would wish to add components from the psychological or social domain. Supported by results from the literature search, a new integral operational definition of frailty was developed. This operational definition lies at the heart of an integral conceptual working model of frailty. This model expresses the relationships between three domains of frailty, adverse outcomes such as disability and the determinants. The model should be able to serve as a basis for further scientific research on frailty. The model also provides a framework for the development of a measurement instrument which can be used for the identification of frail elderly persons.


A Four-Step Method for the Development of an ADHD-VR Digital Game Diagnostic Tool Prototype for Children Using a DL Model.
Attention-deficit/hyperactivity disorder (ADHD) is a common neurodevelopmental disorder among children resulting in disturbances in their daily functioning. Virtual reality (VR) and machine learning technologies, such as deep learning (DL) application, are promising diagnostic tools for ADHD in the near future because VR provides stimuli to replace real stimuli and recreate experiences with high realism. It also creates a playful virtual environment and reduces stress in children. The DL model is a subset of machine learning that can transform input and output data into diagnostic values using convolutional neural network systems. By using a sensitive and specific ADHD-VR diagnostic tool prototype for children with DL model, ADHD can be diagnosed more easily and accurately, especially in places with few mental health resources or where tele-consultation is possible. To date, several virtual reality-continuous performance test (VR-CPT) diagnostic tools have been developed for ADHD; however, they do not include a machine learning or deep learning application. A diagnostic tool development study needs a trustworthy and applicable study design and conduct to ensure the completeness and transparency of the report of the accuracy of the diagnostic tool. The proposed four-step method is a mixed-method research design that combines qualitative and quantitative approaches to reduce bias and collect essential information to ensure the trustworthiness and relevance of the study findings. Therefore, this study aimed to present a brief review of a ADHD-VR digital game diagnostic tool prototype with a DL model for children and the proposed four-step method for its development.


A randomized trial comparing 2 doses of polidocanol sclerotherapy for hydrocele or spermatocele.
Polidocanol sclerotherapy for hydrocele or spermatocele combines high efficiency with low morbidity, but the optimal dose is not known. We compared the efficacy and morbidity of 2 or 4 ml polidocanol sclerotherapy for hydrocele or spermatocele. From 1993 to 2005 a double-blind randomized clinical trial was conducted using 2 or 4 ml polidocanol (30 mg/ml) for sclerotherapy of hydrocele/spermatocele in 224 evaluable patients at 3 university hospitals. Fluid was evacuated and 2 or 4 ml polidocanol was administered by a nurse, with the amount injected concealed from others present. At 3-month followup morbidity was ascertained using a questionnaire completed by the patients. Fluid recurrence was determined clinically and generally re-treated. After the first treatment, cure was observed in 59% and 47% in the 4 and the 2 ml group, respectively (p = 0.04). More patients in the 4 ml group had complications (31% vs 18%, p = 0.04). Complications were mostly of low or moderate intensity and seldom required medication. After 1 to 4 treatments 200 of 224 patients (89%) were cured and another 10 (5%) had small amounts of residual fluid, with no difference between the groups. Of the patients with hydroceles/spermatoceles larger than 175 ml, 58% and 34% were cured after the first treatment in the 4 and 2 ml groups, respectively (p = 0.012), with no differences in complications between the groups. Polidocanol sclerotherapy was effective for the treatment of hydrocele or spermatocele in our patients, with 94% satisfactory results after 1 to 4 treatments. A dose of 4 ml was superior to 2 ml, particularly for larger hydroceles/spermatoceles.


Correlation of erythrocytic peripheral blood chimaerism and putative bone marrow precursors bearing erythroid differentiation (B-G) antigens using monoclonal antibodies immobilized on fluorescent latex spheres.
The degree of erythroid chimaerism from chickens made chimaeric following stem cell infusion as embryos has been determined using a sensitive and simple procedure with monoclonal antibodies (MAbs) specific for erythroid differentiation (B-G) antigens. Highly labelled fluorescent latex beads coupled to specific MAbs have allowed for the detection of very low frequency chimaeric cell subpopulations. A direct correlation between the chimaerism of the bone marrow cells, from which mature RBCs had been eliminated, and the percentage RBC chimaerism in the blood was found. This comprises additional evidence that the B-G bearing bone marrow cells are precursors for mature RBCs.


Effect of surgically-induced weight loss on leukocyte indicators of chronic inflammation in morbid obesity.
Recent evidence suggests that morbid obesity is a chronic inflammatory condition that may be associated with immune dysfunction. To test this hypothesis, we investigated several leukocyte cell surface markers of chronic inflammation and followed their response to surgically-induced weight loss. 26 patients having Roux-en-Y gastric bypass (RYGBP) for morbid obesity (BMI > 40) were compared to 10 normal controls (BMI < 25). Relative monocyte and neutrophil frequencies and expression of the activation antigens CD11b (adhesion molecule), CD16 (Fc receptor), and CD62L (L-selectin), were evaluated by flow cytometry preoperatively and at 1, 3, 6 and 12 months after RYGBP. Cases served as their own controls but were also compared to non-obese controls. The results were statistically analyzed using Student's t-test and ANOVA for parametric values and Mann-Whitney along with Kruskal-Wallis ANOVA for nonparametric values. The control group had mean age 37 +/- 7.6 with mean 23 +/- 2.5 and no comorbidities. The mean age of the sample group was 40.36 +/- 13.7 with mean BMI 52 +/- 8.2. The neutrophil and monocyte relative frequencies of CD11b (monocytes and neutrophils), and CD16 (neutrophils only) were comparable to controls at baseline and did not change significantly with weight loss throughout the study period. However, a significant reduction of CD62L (L-selectin) expression was noted in monocytes and neutrophils at baseline (neutrophils 103 vs 240 gmf, p < 0.001) (monocytes 104 vs 246 gmf, P < 0.001) when compared to normal controls. Levels of L-selectin normalized by 6 months in both monocytes and neutrophils, and by 12 months had become abnormally elevated in monocytes (monocytes 391 gmf, P = 0.007); in neutrophils, there was an upward trend that did not reach significance. The expression of the LPS receptor CD14 in the study group was elevated significantly compared to controls at baseline (1129 vs 719 gmf, P = 0.004); this marker appeared to return to normal by 3 months. Monocyte CD14+/CD16+ subset percentage were also elevated significantly at baseline (14.3% vs 5.25%, P < 0.001), declined throughout the time period but was still significant at 1 year (8.8%, P < 0.001). Eosinophil percentages were elevated at baseline (3.3% obese vs 1.8% controls, P = 0.003) and remained so throughout the time period. Deficiencies in the immune system of morbidly obese individuals include elevated levels of eosinophils, monocyte CD14, and monocyte CD14+/CD16+ subsets, with depression of monocyte and neutrophil CD62L. These abnormal levels reverse rapidly with surgically-induced weight loss. RYGBP is not only a weight loss operation but also appears to be an immune restorative procedure.


User charges in government health facilities in Kenya: effect on attendance and revenue.
In this paper we study demand effects of user charges in a district health care system using cross-sectional data from household and facility surveys. The effects are examined in public as well as in private health facilities. We also look briefly at the impact of fees on revenue and service quality in government facilities. During the period of cost-sharing in public clinics, attendance dropped by about 50%. This drop prompted the government to suspend the fees for approximately 20 months. Over the 7 months after suspension of fees, attendance at government health centres increased by 41%. The suspension further caused a notable movement of patients from the private sector to government health facilities. The revenue generated by user fees covered 2.4% of the recurrent health budget. Some 40% of the facilities did not spend the fee revenue they collected, mainly due to cumbersome procedures of expenditure approvals. The paper concludes with lessons from Kenya's experience with user charges.


Multiscale effects masked the impact of the COVID-19 pandemic on electricity demand in the United States.
Shelter-in-place orders and business closures related to COVID-19 changed the hourly profile of electricity demand and created an unprecedented source of uncertainty for the grid. The potential for continued shifts in electricity profiles has implications for electricity sector investment and operating decisions that maintain reserve margins and provide grid reliability. This study reveals that understanding this uncertainty requires an understanding of the underlying drivers at the customer-class scale. This paper utilizes three datasets to compare the impacts of COVID-19 on electricity consumption across a range of spatiotemporal and customer scales. At the utility/customer-class scale, COVID-19-induced shutdowns in the spring of 2020 shifted weekday residential load profiles to resemble weekend profiles from previous years. Total commercial loads declined, but the commercial diurnal load profile was unchanged. With only total loads available at the balancing authority scale, the apparent impact of COVID-19 was smaller during the summer due in part to phased re-opening and spatial variability in re-opening, but there were still clear variations once total loads were broken down zonally. Monthly data at the state scale showed an increase in state-level residential electricity sales, a decrease in commercial sales, and a small net decrease in total sales in most states from April-August 2020. Analyses that focus on total load or a single scale may miss important changes that become apparent when the load is broken down regionally or by customer class.


Effects of epinephrine on resting potential in normal and hypertrophied cardiac muscles.
The role of the Na-K pump in the control of cellular ion balance has long been appreciated. Recent studies suggest that the manner in which this ion transport system functions in hypertrophied failing (HF) cardiac muscle is markedly different from that seen in normal muscles. The ability of the sympathetic neurohormone, epinephrine, to modulate membrane potential changes thought to reflect the activity of the Na-K pump in normal and HF cardiac muscle was examined in this study. Specifically rate-related changes in membrane potential (Emax) thought to be associated with the Na-K pump were measured in intact functioning cat papillary muscles. The results of these studies demonstrate that the rate-related changes in Emax thought to be associated with Na-K activity were markedly altered in HF cardiac muscles. Emax in these muscles responded to periods of transient stimulation by first depolarizing and then slowly returning to a new steady state which was depolarized with respect to the initial predrive Emax. Emax in normal muscles also depolarized on drive, but returned to a new steady state more rapidly and eventually hyperpolarized. Epinephrine significantly affected these rate-related changes in Emax in normal muscles by causing all the rates of change in Emax to be increased. In HF muscles, on the other hand, epinephrine had no significant effect on these parameters at the concentration tested. These results suggest that under certain conditions HF cardiac muscle may be incapable of maintaining normal resting membrane potentials. In addition the modulating influence of epinephrine is markedly blunted.


Preliminary study related the incidence of methylprednisolone pulse therapy in patients visited multiple sclerosis clinic located at the isfahan kashani hospital.
To manage relapsing-remitting multiple sclerosis (MS) in the course of acute exacerbations, methylprednisolone (MP) (Medrol or Solu-Medrol), has the ability to lock the injured blood-brain barrier and decrease irritation in the central nervous system. The aim of this preliminary study was to investigate the frequency and time interval related to MP pulse therapy in patients with MS. This Study is conducted in the MS clinic of the Isfahan Kashani hospital, that was carried out on patients (n = 901) from June 2011 to December 2012. Patients who visited MS clinic just for once disinterested from analysis. According to the incidence of MP pulse therapy in females and males, two groups were made. Group 1 included patients with 2-3 times and Group 2 included patients with more than 4 times pulse therapy. Demographical data, pharmacological variables including number and time interval related to pulse therapy for each individual were recorded in dBase. The statistical analyses of d-Base were performed using SPSS. 901 patients in 1592 occasions were studied. The mean age of patients was 34.6 years old (ranged: 8-87 years old). 586 patients included 465 females and 121 males visited MS clinic just for once. 245 females in 797 occasions and 70 males in 209 occasions received pulse therapy with a mean of 4 times (ranged: 2-11 times). 51.1% and 48.9% of patients received MP pulse therapy for two and more than two up to 11 times respectively. In the 70% of the patients' time interval between pulse therapy was with a mean of 137 days (ranged: 28-480 days). For pulse therapy, it seems that the female subjects refer to clinic are approximately 3.7 times higher than male subjects. To reduce the demand of patients to pulse therapy, disease management could be rationalized on the basis of illness expansion and its correlation to inter and intra individual variability. Finally, to understand the effectiveness of pharmacotherapy, in MS population (Isfahan/Iran), clinical neuropharmacology in relation to better understand of the individualized pharmacokinetics could be useful.


Effect of broad- and narrow-spectrum antimicrobials on Clostridium difficile and microbial diversity in a model of the distal colon.
Vancomycin, metronidazole, and the bacteriocin lacticin 3147 are active against a wide range of bacterial species, including Clostridium difficile. We demonstrate that, in a human distal colon model, the addition of each of the three antimicrobials resulted in a significant decrease in numbers of C. difficile. However, their therapeutic use in the gastrointestinal tract may be compromised by their broad spectrum of activity, which would be expected to significantly impact on other members of the human gut microbiota. We used high-throughput pyrosequencing to compare the effect of each antimicrobial on the composition of the microbiota. All three treatments resulted in a decrease in the proportion of sequences assigned to the phyla Firmicutes and Bacteroidetes, with a corresponding increase in those assigned to members of the Proteobacteria. One possible means of avoiding such "collateral damage" would involve the application of a narrow-spectrum antimicrobial with specific anti-C. difficile activity. We tested this hypothesis using thuricin CD, a narrow-spectrum bacteriocin produced by Bacillus thuringiensis, which is active against C. difficile. The results demonstrated that this bacteriocin was equally effective at killing C. difficile in the distal colon model but had no significant impact on the composition of the microbiota. This offers the possibility of developing a targeted approach to eliminating C. difficile in the colon, without collateral damage.


Thick acellular heart extracellular matrix with inherent vasculature: a potential platform for myocardial tissue regeneration.
The decellularization of porcine heart tissue offers many opportunities for the production of physiologically relevant myocardial mimetic scaffolds. Earlier, we reported the successful isolation of a thin porcine cardiac extracellular matrix (pcECM) exhibiting relevant bio-mechanical properties for myocardial tissue engineering. Nevertheless, since native cardiac tissue is much thicker, such thin scaffolds may offer limited regeneration capacity. However, generation of thicker myocardial mimetic tissue constructs is hindered by diffusion limitations (~100 μm), and the lack of a proper vascular-like network within these constructs. In our present work, we focused on optimizing the decellularization procedure for thicker tissue slabs (10-15 mm), while retaining their inherent vasculature, and on characterizing the resulting pcECM. The trypsin/Triton-based perfusion procedure that resulted in a nonimmunogenic and cell-supportive pcECM was found to be more effective in cell removal and in the preservation of fiber morphology and structural characteristics than stirring, sonication, or sodium dodecyl sulfate/Triton-based procedures. Mass spectroscopy revealed that the pcECM is mainly composed of ECM proteins with no apparent cellular protein remains. Mechanical testing indicated that the obtained pcECM is viscoelastic in nature and possesses the typical stress-strain profile of biological materials. It is stiffer than native tissue yet exhibits matched mechanical properties in terms of energy dissipation, toughness, and ultimate stress behavior. Vascular network functionality was maintained to the first three-four branches from the main coronary vessels. Taken together, these results reaffirm the efficiency of the decellularization procedure reported herein for yielding thick nonimmunogenic cell-supportive pcECM scaffolds, preserving both native tissue ultra-structural properties and an inherent vascular network. When reseeded with the appropriate progenitor cells, these scaffolds can potentially serve as ex vivo screening platforms for new therapeutics, as models for human cardiac ECM, or as biomedical constructs for patch or transmural transplantation strategies.


Cell-Penetrating Penta-Peptides (CPP5s): Measurement of Cell Entry and Protein-Transduction Activity.
Previously, we developed cell-penetrating penta-peptides (CPP5s). In the present study, VPTLK and KLPVM, two representative CPP5s, were used to characterize the cell-penetration and protein-transduction activities of these small molecules. Various inhibitors of endocytosis and pinocytosis (chlorpromazine, cytochalasin D, Filipin III, amiloride, methyl-β-cyclodextrin, and nocodazole) were tested. Only cytochalasin D showed suppression of CPP5 entry, though the effect was partial. In addition, CPP5s were able to enter a proteoglycan-deficient CHO cell line. These results suggest that pinocytosis and endocytosis may play only a minor role in the cell entry of CPP5s. By mass spectrometry, we determined that the intracellular concentration of VPTLK ranged from 20 nM to 6.0 μM when the cells were cultured in medium containing 1 μM - 1.6 mM VPTLK. To determine the protein-transduction activity of CPP5s, the Tex-LoxP EG cell line, which has a Cre-inducible green fluorescent protein (GFP) gene, was used. VPTLK and KLPVM were added to the N-terminus of Cre, and these fusion proteins were added to the culture medium of Tex-LoxP EG cells. Both VPTLK-Cre and KLPVM-Cre were able to turn on GFP expression in these cells, suggesting that CPP5s have protein-transduction activity. Since CPP5s have very low cytotoxic activity, even at a concentration of 1.6 mM in the medium, CPP5s could be utilized as a new tool for drug delivery into cells.


Three new members of the mouse prolactin/growth hormone family are homologous to proteins expressed in the rat.
A search of a mouse expressed sequence tag database for novel messenger RNAs (mRNAs) in the PRL/GH family has identified three clones that are homologous to the rat PRL-like protein A (PLP-A), PRL-like protein B (PLP-B), and decidual/trophoblast PRL-related protein (d/tPRP). Full-length complementary DNA clones for each of these three mouse mRNAs have been sequenced. Mouse PLP-A is predicted to be synthesized as a precursor of 227 residues and secreted as a glycoprotein of 196 amino acids; the secreted protein shares 78% identity with rat PLP-A. The open reading frame for mouse PLP-B encodes a protein of 230 residues; the putative mature glycoprotein of 201 amino acids is 66% identical to rat PLP-B. The third mouse complementary DNA clone encodes a precursor protein of 240 residues and a secreted glycoprotein of 211 amino acids with 64% identity to rat d/tPRP. All three mouse mRNAs are expressed specifically in the placenta or decidua. The highest levels of the PLP-A mRNA are detected on day 12, at which time expression is localized to a subset of trophoblast giant cells, especially those cells that line maternal blood sinuses. PLP-B mRNA levels are high on day 10 in decidual cells and on day 12 in spongiotrophoblasts. The mRNA similar to rat d/tPRP is present at high levels even earlier in gestation (day 8) and is localized to the decidual layer. The identification of PRL-related mRNAs in common between the mouse and rat indicates that the encoded hormones are evolutionarily conserved and, therefore, likely to play important roles in reproductive physiology.


Hypoxia favors chemoresistance in T-ALL through an HIF1α-mediated mTORC1 inhibition loop.
Resistance to chemotherapy, a major therapeutic challenge in the treatment of T-cell acute lymphoblastic leukemia (T-ALL), can be driven by interactions between leukemic cells and the microenvironment that promote survival of leukemic cells. The bone marrow, an important leukemia niche, has low oxygen partial pressures that highly participate in the regulation of normal hematopoiesis. Here we show that hypoxia inhibits T-ALL cell growth by slowing down cell cycle progression, decreasing mitochondria activity, and increasing glycolysis, making them less sensitive to antileukemic drugs and preserving their ability to initiate leukemia after treatment. Activation of the mammalian target of rapamycin (mTOR) was diminished in hypoxic leukemic cells, and treatment of T-ALL with the mTOR inhibitor rapamycin in normoxia mimicked the hypoxia effects, namely decreased cell growth and increased quiescence and drug resistance. Knocking down (KD) hypoxia-induced factor 1α (HIF-1α), a key regulator of the cellular response to hypoxia, antagonized the effects observed in hypoxic T-ALL and restored chemosensitivity. HIF-1α KD also restored mTOR activation in low O2 concentrations, and inhibiting mTOR in HIF1α KD T-ALL protected leukemic cells from chemotherapy. Thus, hypoxic niches play a protective role of T-ALL during treatments. Inhibition of HIF-1α and activation of the mTORC1 pathway may help suppress the drug resistance of T-ALL in hypoxic niches.


Delayed facial nerve palsy after endolymphatic sac surgery.
Data on delayed facial nerve palsy (DFNP) following endolymphatic sac enhancement surgery are limited. We conducted a retrospective chart review to determine the incidence, possible predisposing factors, treatment, and prognosis of DFNP in such cases. We reviewed the records of 779 patients who had undergone endolymphatic sac surgery for intractable Ménière disease from January 1997 through December 2007 at a tertiary care otologic referral center. We found 5 cases (0.64%) of postoperative DFNP. The length of time between surgery and the onset of DFNP ranged from 7 to 20 days (mean: 11). Paralysis was incomplete in all 5 patients. Four of these patients had an abnormal mastoid bone anatomy, as the sigmoid sinus was either anteriorly or anteromedially displaced. The 5 patients had been treated with a steroid, either with or without an antiviral, and all 5 experienced a complete recovery of facial nerve function within 8 weeks of the onset of their paralysis. It is difficult to delineate the exact etiology of DFNP following endolymphatic sac surgery, but we speculate that factors such as physical injury to the nerve and/or a viral reactivation might have played a role. Also, the unusual mastoid bone anatomy seen in 4 of these patients might have been responsible, as well.


Histone deacetylase 6: at the interface of cancer and neurodegeneration.
With the recognition in the early 1960s that histones can be post-translationally modified, the list of different post-translational modifications of histones and their biological consequences has continued to expand. In addition, the idea of the 'histone code' hypothesis, later introduced by David Allis and colleagues, further broaden the horizon of chromatin biology. Currently, there is a wealth of knowledge about the transition between the active and the repressive state of chromatin, and modifications of histones remains at the center of chromatin biology. Histone deacetylases (HDACs) in particular are of great importance for the therapeutic success of cancer treatment. Focusing primarily on HDAC6, herein we have briefly highlighted its unique involvement in cancer and also apparently in neurodegeneration.


Understanding the support needs of family members of people undergoing chemotherapy: A longitudinal qualitative study.
Capture change in family members' experiences as they look after patients during chemotherapy, and understand variability in their needs for support. Longitudinal digitally-recorded qualitative semi-structured interviews with family carers at the beginning, mid-point, and end of treatment. Twenty-five family members (17 women, 8 men), mean age 53, were interviewed. Fifteen participants were supporting a relative having chemotherapy with curative intent, and 10 a patient receiving palliative chemotherapy. They were recruited from two UK locations: a regional cancer centre in Southampton and a comprehensive cancer centre in London. Sixty-three interviews were conducted in total, and the data were analysed using Framework Analysis. Three themes were generated from the data: Changing lives, Changing roles; Confidence in caring, and Managing uncertainty. These captured family carers' evolving needs and sense of confidence in caregiving during chemotherapy. Carers reported considerable anxiety at the outset of treatment which persisted throughout. Anxiety was underpinned by fears of disease recurrence or progression and concerns about treatment outcomes. This study presents original fine-grained work that captures the changes over time in family carers' experiences of chemotherapy and their adaptation to caregiving. It provides fundamental evidence of the challenges that cancer carers face during patients' treatment; evidence that can be used as a basis for carer assessment and to build much-needed carer interventions. Oncology nurses should assess carers': ability to care; needs for information and support to prepare them for this; wellbeing over time; and, any support they may require to prevent them from becoming overburdened.


Management of giardiasis.
Giardia lamblia is the most common cause of infectious diarrhea in the world. In the United States, it has been cited as the cause of several epidemics of waterborne disease. The organism has cyst and trophozoite forms, but only the cyst can exist outside the host. The gastrointestinal symptoms of giardiasis are usually self-limited, but chronic cases may occur. Patient education helps reduce public anxiety during an epidemic.


A National Cross-Sectional Study of Surgery Residents Who Underreport Duty Hours.
Previous work demonstrates that many surgery residents underreport duty hours. The purpose of this study was to identify characteristics of these residents and better understand why they exceed duty hours. During the winter of 2015 we conducted an anonymous cross-sectional survey of Accreditation Council for Graduate Medical Education accredited general surgery programs. A total of 101 general surgery residency programs across the United States. A total of 1003 general surgery residents across the United States. Respondents' mean age was 29.9 ± 3.0 years; 53% were male. Study response rate was 31.9%. Residents age <30 were more likely to exceed duty hours to complete charting/documentation (68% vs. 54%, p < 0.001). Females more often cited guilt about leaving the hospital (32% vs. 24%, p = 0.014) as to why they exceed duty hours. Programs with >40 residents had the highest rates of underreporting (82% vs. 67% in other groups p < 0.001) and residents who worked >90 hours on an average week more frequently cited external pressure (p = 0.0001), guilt (p = 0.006), and feeling it was expected of them (p < 0.0001) as reasons why they underreport compared to those who worked fewer hours. Underreporting and duty-hour violations are a complex issue influenced by many variables including age, sex, and internal and external pressures.


Propagation of genetically altered tumor cells derived from fine-needle aspirates of primary breast carcinoma.
Because primary breast tumors are diagnosed earlier in the clinic, procurement of sufficient amounts of tumor tissue for in-depth biological characterization is becoming increasingly difficult. We demonstrate here that relatively small numbers of tumor cells within samples of fine-needle aspirates (FNA) can be propagated in culture. Of 25 cases attempted, 12 were passageable, resulting in up to 10(7) viable cells. FNA-derived cultures were evaluated for anchorage-independence, c-erb-B2 overexpression, aneusomy, and pattern of allelic loss. In every case examined, the cultured cells closely resembled the original tumor tissue and displayed one or more tumor phenotypes. The incidence of erb-B2 overexpressing tumors was similar in passageable and nonpassageable cases (33% versus 31%, respectively). FNAs that are expanded from a wide range of clinical breast material could be useful for functional studies presently limited to rare established cell lines, such as aberrant signal transduction and gene regulation, and for testing potential anticancer vaccines and drugs.


Randomized intergroup trial of cisplatin-paclitaxel versus cisplatin-cyclophosphamide in women with advanced epithelial ovarian cancer: three-year results.
A randomized trial conducted by the Gynecologic Oncology Group (GOG, study #111) in the United States showed a better outcome for patients with advanced ovarian cancer on the paclitaxel-cisplatin regimen than for those on a standard cyclophosphamide-cisplatin regimen. Before considering the paclitaxel-cisplatin regimen as the new "standard," a group of European and Canadian investigators planned a confirmatory phase III trial. This intergroup trial recruited 680 patients with broader selection criteria than the GOG #111 study and administered paclitaxel as a 3-hour instead of a 24-hour infusion; progression-free survival was the primary end point. Patient survival was analyzed by use of the Kaplan-Meier technique. Treatment effects on patient survival were estimated by Cox proportional hazards regression models. All statistical tests were two-sided. The overall clinical response rate was 59% in the paclitaxel group and 45% in the cyclophosphamide group; the complete clinical remission rates were 41% and 27%, respectively; both differences were statistically significant (P =.01 for both). At a median follow-up of 38.5 months and despite a high rate of crossover (48%) from the cyclophosphamide arm to the paclitaxel arm at first detection of progression of disease, a longer progression-free survival (log-rank P =.0005; median of 15.5 months versus 11.5 months) and a longer overall survival (log-rank P =. 0016; median of 35.6 months versus 25.8 months) were seen in the paclitaxel regimen compared with the cyclophosphamide regimen. There is strong and confirmatory evidence from two large randomized phase III trials to support paclitaxel-cisplatin as the new standard regimen for treatment of patients with advanced ovarian cancer.


Screening mammography: test set data can reasonably describe actual clinical reporting.
To establish the extent to which test set reading can represent actual clinical reporting in screening mammography. Institutional ethics approval was granted, and informed consent was obtained from each participating screen reader. The need for informed consent with respect to the use of patient materials was waived. Two hundred mammographic examinations were selected from examinations reported by 10 individual expert screen readers, resulting in 10 reader-specific test sets. Data generated from actual clinical reports were compared with three test set conditions: clinical test set reading with prior images, laboratory test set reading with prior images, and laboratory test set reading without prior images. A further set of five expert screen readers was asked to interpret a common set of images in two identical test set conditions to establish a baseline for intraobserver variability. Confidence scores (from 1 to 4) were assigned to the respective decisions made by readers. Region-of-interest (ROI) figures of merit (FOMs) and side-specific sensitivity and specificity were described for the actual clinical reporting of each reader-specific test set and were compared with those for the three test set conditions. Agreement between pairs of readings was performed by using the Kendall coefficient of concordance. Moderate or acceptable levels of agreement were evident (W = 0.69-0.73, P < .01) when describing group performance between actual clinical reporting and test set conditions that were reasonably close to the established baseline (W = 0.77, P < .01) and were lowest when prior images were excluded. Higher median values for ROI FOMs were demonstrated for the test set conditions than for the actual clinical reporting values; this was possibly linked to changes in sensitivity. Reasonable levels of agreement between actual clinical reporting and test set conditions can be achieved, although inflated sensitivity may be evident with test set conditions.


Pharmacological inhibition of poly(ADP-ribose) polymerase activity down-regulates the expression of syndecan-4 and Id-1 in endothelial cells.
Poly(ADP-ribose) polymerase (PARP) is a family of nuclear proteins which regulate a number of cell functions, such as DNA repair, transcription, remodelling of chromatin structure, cell division and cell death. We and others have recently demonstrated that down-regulation of cellular PARP activity, using pharmacological inhibitors, impairs a number of endothelial functions and angiogenesis. In the present study, we investigated the potential mechanisms underlying the anti-angiogenic effect exerted by the potent PARP inhibitor GPI 15427, analyzing gene expression in human endothelial cells shortly after treatment with this compound. Analysis of gene and protein expression indicated that a 2-h exposure of human endothelial cells to GPI 15427 induced a rapid decrease of syndecan-4 (SDC-4), a transmembrane protein involved in modulation of cell signalling during angiogenesis that plays a role in endothelial cell migration and adhesion. Moreover, treatment with the PARP inhibitor induced a reduction of a helix-loop-helix transcription factor, the inhibitor of DNA binding-1 (Id-1), also implicated in the control of endothelial functions. We suggest that the inhibitory effect exerted by GPI 15427 on the angiogenic process is likely due to the reduced activity of specific transcription factors, such as Oct-1 and CREB that contribute to the regulation of SDC-4 and Id-1 expression, respectively. In conclusion, these results strongly suggest that PARP activity is capable of modulating molecules required for endothelial cell migration, adhesion, proliferation or differentiation during the angiogenic process.


The dynamics of the human immunodeficiency virus epidemics in the south of Brazil: increasing role of injection drug users.
Changes in human immunodeficiency virus (HIV) infection among injection drug users (IDUs) are provoking a shift in the pattern of the HIV/AIDS epidemic in some regions of Brazil. IDUs living in 2 cities (Porto Alegre and Itajaí) in southern Brazil were contacted, interviewed, and tested for HIV. In 1998, 187 IDUs were surveyed and, in 2000, 352 IDUs. In Porto Alegre, HIV seroprevalence, age, and duration of injection history increased significantly over time. In contrast, a trend toward decline was observed in Itajaí. Homelessness, joblessness, and prison incarceration, as well as lifetime needle sharing, also increased over time in Porto Alegre. At the time of the study, at both sites, rates of needle sharing and condom use were similar, but use of syringe exchange programs, health and drug treatment, and HIV testing had increased over time. IDUs living in southern Brazil are at increased risk of HIV infection, indicating the continued need for permanent surveillance and preventive strategies.


Creating Engaging Health Promotion Campaigns on Social Media: Observations and Lessons From Fitbit and Garmin.
The popularity and reach of social media make it an ideal delivery platform for interventions targeting health behaviors, such as physical inactivity. Research has identified a dose-response relationship whereby greater engagement and exposure are positively associated with intervention effects, hence enhancing engagement will maximize the potential of these interventions. This study examined the social media activity of successful commercial activity tracker brands to understand which creative elements (message content and design) they use in their communication to their audience, which social media platforms attract the most engagement, and which creative elements prompted the most engagement. Posts (n=509) made by Fitbit and Garmin on Facebook, Twitter, and Instagram over a 3-month period were coded for the presence of creative elements. User engagement regarding the total number of likes, comments, or shares per post was recorded. Negative binomial regression analyses were used to identify creative elements associated with higher engagement. Engagement on Instagram was 30-200 times higher than on Facebook, or Twitter. Fitbit and Garmin tended to use different creative elements from one another. A higher engagement was achieved by posts featuring an image of the product, highlighting new product features and with themes of self-improvement (P<.01). Findings suggest that Instagram may be a particularly promising platform for delivering engaging health messaging. Health messages which incorporate inspirational imagery and focus on a tangible product appear to achieve the highest engagement. Fitbit and Garmin employed difference creative elements, which is likely to reflect differences in their target markets. This underscores the importance of market segmentation in health messaging campaigns.


Evidence for abnormalities in separate lymphocyte populations in NZB mice.
Neonatally thymectomized, lethally irradiated NZB X DBA/2 and DBA/2 X NZB F1 mice were reconstituted with NZB or DBA/2 bone marrow cells and NZB or DBA2 thymocytes. Of the four resulting groups of recipient F1 mice, those given NZB bone marrow cells developed high serum IgM levels, irrespective of the thymocyte donor strain. In contrast, recipients of NZB thymocytes were resistant to induction of tolerance to BCG, irrespective of the bone marrow donor strain. Only recipients of NZB bone marrow cells made spontaneous antierythrocyte autoantibodies; of these, the responses of NZB thymocyte recipients were greater and more consistent than those of DBA/2 thymocyte recipients. Recipients of either NZB bone marrow cells or NZB thymocytes made antibody responses to ssDNA; the highest anti-ssDNA responses occurred in recipients of both NZB bone marrow cells and NZB thymocytes. We conclude that functional abnormalities in separate lymphocyte populations underlie different immune abnormalities in NZB mice.


Numbers of asbestos bodies on iron-stained tissue sections in relation to asbestos body counts in lung tissue digests.
Utilization of tissue digestion techniques has demonstrated the presence of large numbers of asbestos bodies within lungs of persons after occupational exposure to asbestos, and smaller numbers in the vast majority of persons with no identifiable exposure. Because of the wide variability in results of such studies among different observers, the presence of more than one asbestos body on light microscopy has been recommended recently as one of the morphologic requirements (together with peribronchiolar fibrosis) for the tissue diagnosis of asbestosis. However, data that correlate the occurrence of asbestos bodies in paraffin-embedded tissue sections with the quantification of asbestos bodies by tissue digestion techniques have not been available. The authors counted the asbestos bodies in multiple paraffin-embedded sections of lung tissues stained for iron, and compared those numbers with the asbestos body counts determined by hypochlorite digestion of wet formalin-fixed lung tissue in six cases of asbestosis or asbestos-associated neoplasia. When adjustments were made for asbestos body orientation in tissue sections, shrinkage of sections during processing, and conversion of lung volume to wet weight, the agreement between the two techniques was excellent (r = 0.98, P less than 0.001). An average of two asbestos bodies on 2 X 2 cm (4 cm2) iron-stained tissue sections 5 microns thick is equivalent to approximately 200 asbestos bodies per gram of wet fixed lung tissue.


Growth and dissemination of human malignant lymphoblasts in immunosuppressed nu/nu mice.
Athymic nu/nu mice are commonly employed for the heterotransplantation of solid human tumors. Leukemias, however, have consistently proved difficult to transplant and, to enhance their take, recipient nu/nu mice have been variously immunosuppressed. In this study, the natural reactivity against human malignant T lymphoblast (PF382) of splenectomized nu/nu mice (S-nu/nu), nu/nu mice splenectomized and treated with polyinosinic-polycytidylic acid (SIC-nu/nu), and nu/nu mice splenectomized, irradiated and repeatedly injected with antiasialo GM1 antiserum (SIA-nu/nu) has been correlated with the in vivo growth of subcutaneous and intravenous PF382 cell challenges. SIC-nu/nu mice display a marked natural killer (NK) activity, quickly clear 125I-Urd-labelled PF382 cells injected intravenously and do not allow the growth of subcutaneous nor intravenous PF382 cell challenges. S-nu/nu mice display a slightly lower NK activity and slower clearance of 125I-Urd-labelled PF382 cells. Moreover, an intravenous PF382 cell challenge kills 56% of S-nu/nu mice. SIA-nu/nu mice have no NK activity, slowly clear 125I-Urd-labelled PF382 cells and always allow the growth of PF382 cells injected either subcutaneously or intravenously with a consistent pattern. Following the intravenous challenge, PF382 cells first metastasize to liver and kideny, then focal or diffuse infiltrations of the bone marrow and menings become evident. SIA-nu/nu mice thus offer an interesting experimental model for study of the pathogenesis of leukemic infiltration of the meninges, and the exploration of possible therapeutic approaches.


Cardiovascular lesions in pancreatitis.
Data have been presented correlating changes of blood coagulability, capillary permeability, blood electrolyte content with electrocardiographic abnormalities and symptoms of coronary insufficiency. In acute pancreatitis and in acute exacerbation of chronic pancreatitis, accentuation of these vascular factors may induce symptoms of coronary disease. Data are also presented indicating abnormal blood coagulability and blood electrolyte content in patients with chronic pancreatitis. Minimal augmentation of these abnormalities may account for the "yoke" syndrome.


Spontaneous Rupture of Lacrimal Gland Pleomorphic Adenoma: Pivotal Role in Masquerading Orbital Cellulitis.
The authors aim to report a 68-year-old patient presenting with acute swelling and redness of orbital area diagnosed initially as orbital cellulitis. Surgical excision was decided based on clinical and imaging findings with the diagnosis of pleomorphic adenoma of the lacrimal gland. Lacrimal gland pleomorphic adenoma usually presents with painless gradual swelling of upper eyelid. In an exceptionally rare circumstance, this case showed acute orbital inflammation, and imaging findings of orbital inflammation mostly focused around the cystic space of the lacrimal gland tumor. Histologic evaluation confirmed a ruptured cystic space of pleomorphic adenoma with foreign body-type inflammatory reaction. The authors propose spontaneous rupture of cystic space in the lacrimal gland pleomorphic adenoma as underlying mechanism for acute presentation of this tumor. Imaging and clinical characteristics and also prognostic implication of this phenomenon are discussed.


Cervical Cancer Screening among Women from Muslim-Majority Countries in Ontario, Canada.
Background: Immigrant women are less likely to be screened for cervical cancer in Ontario. Religion may play a role for some women. In this population-based retrospective cohort study, we used country of birth as a proxy for religious affiliation and examined screening uptake among foreign-born women from Muslim-majority versus other countries, stratified by region of origin.Methods: We linked provincial databases and identified all women eligible for cervical cancer screening between April 1, 2012, and March 31, 2015. Women were classified into regions based on country of birth. Countries were classified as Muslim-majority or not.Results: Being born in a Muslim-majority country was significantly associated with lower likelihood of being up-to-date on Pap testing, after adjustment for region of origin, neighborhood income, and primary care-related factors [adjusted relative risk (ARR), 0.93; 95% (confidence interval) CI, 0.92-0.93]. Sub-Saharan African women from Muslim-majority countries had the highest prevalence of being overdue (59.6%), and the lowest ARR for screening when compared with women from non-Muslim-majority Sub-Saharan African countries (ARR, 0.77; 95% CI, 0.76-0.79). ARRs were lowest for women with no primary care versus those in a capitation-based model (ARR, 0.28; 95% CI, 0.27-0.29 overall).Conclusions: We have shown that being born in a Muslim-majority country is associated with a decreased likelihood of being up-to-date on cervical screening in Ontario and that access to primary care has a sizeable impact on screening uptake.Impact: Screening efforts need to take into account the background characteristics of population subgroups and to focus on increasing primary care access for all. Cancer Epidemiol Biomarkers Prev; 26(10); 1493-9. ©2017 AACR.


Thought outside the box: intensive care unit freakonomics and decision making in the intensive care unit.
Despite concerted efforts to improve the quality of care provided in the intensive care unit, inconsistency continues to characterize physician decision making. The resulting variations in care compromise outcomes and impose unnecessary decisional regret on clinicians and patients alike. Critical care is not the only arena where decisions fail to conform to the dictates of logic. Behavioral psychology uses scientific methods to analyze the influence of social, cognitive, and emotional factors on decisions. The overarching hypothesis underlying this "thought outside the box" is that the application of behavioral psychology to physician decision making in the intensive care unit will demonstrate the existence of cognitive biases associated with classic intensive care unit decisions; provide insight into novel strategies to train intensive care unit clinicians to better use data; and improve the quality of decision making in the intensive care unit as characterized by more consistent, patient-centered decisions with reduced decisional regret and work-related stress experienced by physicians.


Efficient identification of transcription factor binding sites with a graph theoretic approach.
Identifying transcription factor binding sites with experimental methods is often expensive and time consuming. Although many computational approaches and tools have been developed for this problem, the prediction accuracy is not satisfactory. In this paper, we develop a new computational approach that can model the relationships among all short sequence segments in the promoter regions with a graph theoretic model. Based on this model, finding the locations of transcription factor binding site is reduced to computing maximum weighted cliques in a graph with weighted edges. We have implemented this approach and used it to predict the binding sites in two organisms, Caenorhabditis elegans and mus musculus. We compared the prediction accuracy with that of the Gibbs Motif Sampler. We found that the accuracy of our approach is higher than or comparable with that of the Gibbs Motif Sampler for most of tested data and can accurately identify binding sites in cases where the Gibbs Motif Sampler has difficulty to predict their locations.


Cyclic-AMP-dependent protein kinase (PKA) in testicular cells. Cell specific expression, differential regulation and targeting of subunits of PKA.
LH and FSH regulate via cyclic adenosine 3'5' cyclic monophosphate (cAMP) and cAMP-dependent protein kinase (PKA), steroid biosynthesis is Leydig and Sertoli cells, respectively. Cyclic AMP also regulates a number of different cellular processes such as cell growth and differentiation, ion channel conductivity, synaptic release of neurotransmitters, and gene transcription. The principle intracellular target for cAMP in mammalian cells is the PKA. The fact that this broad specificity protein kinase mediates a number of discrete physiological responses following cAMP engagement, has raised the question of how specificity is maintained in the cAMP/PKA system. Here we describe features of this signaling pathway that may contribute to explain how differential effects of cAMP may occur.


High malaria transmission in a forested malaria focus in French Guiana: How can exophagic Anopheles darlingi thwart vector control and prevention measures?
In French Guiana, malaria vector control and prevention relies on indoor residual spraying and distribution of long lasting insecticidal nets. These measures are based on solid epidemiological evidence but reveal a poor understanding of the vector. The current study investigated the behaviour of both vectors and humans in relation to the ongoing prevention strategies. In 2012 and 2013, Anopheles mosquitoes were sampled outdoors at different seasons and in various time slots. The collected mosquitoes were identified and screened for Plasmodium infection. Data on human behaviour and malaria episodes were obtained from an interview. A total of 3,135 Anopheles mosquitoes were collected, of which Anopheles darlingi was the predominant species (96.2%). For the December 2012-February 2013 period, the Plasmodium vivax infection rate for An. darlingi was 7.8%, and the entomological inoculation rate was 35.7 infective bites per person per three-month span. In spite of high bednet usage (95.7%) in 2012 and 2013, 52.2% and 37.0% of the participants, respectively, had at least one malaria episode. An. darlingi displayed heterogeneous biting behaviour that peaked between 20:30 and 22:30; however, 27.6% of the inhabitants were not yet protected by bednets by 21:30. The use of additional individual and collective protective measures is required to limit exposure to infective mosquito bites and reduce vector densities.


Prevalence and Risk Factors of Chronic Obstructive Pulmonary Disease Among Agriculturists in a Rural Community, Central Thailand.
The present study aimed to determine the prevalence and risk factors of chronic obstructive pulmonary disease (COPD) among agriculturists in a remote rural community in central Thailand. A cross-sectional study was conducted in January 2020. Face-to-face interviews were conducted using standardized questionnaires to determine demographic characteristics and risk behaviors. COPD was defined by the spirometric criterion for airflow limitation constituting a postbronchodilator fixed ratio of FEV1/FVC <0.70 following the Global Initiative for Chronic Obstructive Lung Disease (GOLD) guidelines 2019. Multivariable logistic regression analysis was used to determine the risk factors for COPD, and the magnitude of association was presented as adjusted odds ratio (AOR) with 95% confidence interval (95% CI). A total of 546 agriculturists were enrolled in the study. The overall prevalence of COPD was 5.5% (95% CI: 3.6-7.4). The prevalence of COPD among males was 8.0% (95% CI: 4.7-11.3), and 3.2% (95% CI: 1.1-5.2) among females. The risk factors of COPD included age ≥60 years old (AOR 2.7, 95% CI: 1.1-7.0), higher intensity of smoking (AOR 1.1, 95% CI: 1.0-1.1), swine farm worker (AOR 4.1, 95% CI: 1.7-10.3), cattle farm worker (AOR 3.3, 95% CI: 1.4-8.2) and home cooking (AOR 2.7, 95% CI: 0.8-9.7). Our data emphasized that COPD was one of the significant health problems among agriculturists in a rural community. Agricultural jobs such as animal farmers and behavioral factors such as smoking were associated with COPD. Effective public health interventions, especially, modifying risk behaviors, should be promoted in remote rural areas to prevent the disease and reduce its morbidity and mortality.


Exploring nursing assistants' roles in the process of pain management for cognitively impaired nursing home residents: a qualitative study.
To explore nursing assistants' roles during the actual process of pain management (assessment, reporting, implementation of pain-relieving interventions and re-assessment) for cognitively impaired home residents with pain. Nursing assistants provide most of the direct care to residents and represent the major taskforce in nursing homes. They may develop specialized knowledge of residents' pain experience that enables them to play both a pivotal role in pain assessment and possibly a supporting role in pain treatment. Currently, there is a lack of research into nursing assistants' functions in pain management. This is a descriptive, exploratory qualitative study. Forty-nine nursing assistants were recruited from 12 nursing homes, 12 of them participating in semi-structured individual interviews and 37 in 8 semi-structured focus groups. All interviews were carried out from May to September 2010. Data collected via both data collection methods were transcribed verbatim and analysed by content analysis. Nursing assistants were found to play four roles in the pain management process: (1) pain assessor; (2) reporter; (3) subordinate implementing prescribed medications; and (4) instigator implementing non-pharmacological interventions. This study highlights the importance of nursing assistants in successful pain assessment and identifies their possible supporting roles in other aspects of pain management. However, nursing assistants' scope of practice resulted in their functions in pain management being continually undervalued by other healthcare professionals. Continuous in-service training, the use of a standardized pain management protocol and strategies for building coherent work teams in nursing homes are suggested to improve this situation.


A unique data analysis framework and open source benchmark data set for the analysis of comprehensive two-dimensional gas chromatography software.
Comprehensive two-dimensional gas chromatography (GC × GC) is amongst the most powerful separation technologies currently existing. Since its advent in early 1990, it has become an established method which is readily available. However, one of its most challenging aspects, especially in hyphenation with mass spectrometry is the high amount of chemical information it provides for each measurement. The GC × GC community agrees that there, the highest demand for action is found. In response, the number of software packages allowing for in-depth data processing of GC × GC data has risen over the last couple of years. These packages provide sophisticated tools and algorithms allowing for more streamlined data evaluation. However, these tools/algorithms and their respective specific functionalities differ drastically within the available software packages and might result in various levels of findings if not appropriately implemented by the end users. This study focuses on two main objectives. First, to propose a data analysis framework and second to propose an open-source dataset for benchmarking software options and their specificities. Thus, allowing for an unanimous and comprehensive evaluation of GC × GC software. Thereby, the benchmark data includes a set of standard compound measurements and a set of chocolate aroma profiles. On this foundation, eight readily available GC × GC software packages were anonymously investigated for fundamental and advanced functionalities such as retention and detection device derived parameters, revealing differences in the determination of e.g. retention times and mass spectra.


Improving business IQ in medicine through mentorship and education.
Business intelligence in the field of medicine, particularly with physicians, has been an abstract concept at best with no objective metric. Furthermore, in many arenas, it was taboo for medical students, residents, and physicians to discuss the business and finances of their work for fear that it would interfere with their sacred duties as health care providers. There has been a substantial shift in this philosophy over the last few decades with the growth and evolution of the health care industry in the United States. In 2012, health care expenditures accounted for 17.2% of the United States Gross Domestic Product, averaging $8915 per person. The passage of the Affordable Care Act in March of 2010 sent a clear message to all that change is coming, and it is more important now than ever to have physician leaders whose skills and knowledge in business, management, and health care law rival their acumen within their medical practice. Students, residents, and fellows all express a desire to gain more business knowledge throughout their education and training, but many do not know where to begin or have access to programs that can further their knowledge. Whether you are an employed or private practice physician, academic or community based, improving your business intelligence will help you get a seat at the table where decisions are made and give you the skills to influence those decisions.


The Guinea-Bissau family of Mycobacterium tuberculosis complex revisited.
The Guinea-Bissau family of strains is a unique group of the Mycobacterium tuberculosis complex that, although genotypically closely related, phenotypically demonstrates considerable heterogeneity. We have investigated 414 M. tuberculosis complex strains collected in Guinea-Bissau between 1989 and 2008 in order to further characterize the Guinea-Bissau family of strains. To determine the strain lineages present in the study sample, binary outcomes of spoligotyping were compared with spoligotypes existing in the international database SITVIT2. The major circulating M. tuberculosis clades ranked in the following order: AFRI (n = 195, 47.10%), Latin-American-Mediterranean (LAM) (n = 75, 18.12%), ill-defined T clade (n = 53, 12.8%), Haarlem (n = 37, 8.85%), East-African-Indian (EAI) (n = 25, 6.04%), Unknown (n = 12, 2.87%), Beijing (n = 7, 1.68%), X clade (n = 4, 0.96%), Manu (n = 4, 0.97%), CAS (n = 2, 0.48%). Two strains of the LAM clade isolated in 2007 belonged to the Cameroon family (SIT61). All AFRI isolates except one belonged to the Guinea-Bissau family, i.e. they have an AFRI_1 spoligotype pattern, they have a distinct RFLP pattern with low numbers of IS6110 insertions, and they lack the regions of difference RD7, RD8, RD9 and RD10, RD701 and RD702. This profile classifies the Guinea-Bissau family, irrespective of phenotypic biovar, as part of the M. africanum West African 2 lineage, or the AFRI_1 sublineage according to the spoligtyping nomenclature. Guinea-Bissau family strains display a variation of biochemical traits classically used to differentiate M. tuberculosis from M. bovis. Yet, the differential expression of these biochemical traits was not related to any genes so far investigated (narGHJI and pncA). Guinea-Bissau has the highest prevalence of M. africanum recorded in the African continent, and the Guinea-Bissau family shows a high phylogeographical specificity for Western Africa, with Guinea-Bissau being the epicenter. Trends over time however indicate that this family of strains is waning in most parts of Western Africa, including Guinea-Bissau (p = 0.048).


Mass Spectrometry-based Proteomics in Acute Respiratory Distress Syndrome: A Powerful Modality for Pulmonary Precision Medicine.
Acute respiratory distress syndrome (ARDS) is an acute and lethal clinical syndrome that is characterized by hypoxemic respiratory failure and diffuse alveolar inflammatory damage. This review aimed to search and discuss the mass spectrometry (MS)-based proteomic studies on different subsets of ARDS patients. Original research articles were collected from the PubMed database published in English up to December 2015. The literature search was done using the term "(acute lung injury OR acute respiratory distress syndrome) AND (proteomics OR proteome OR mass spectrum OR differential in-gel electrophoresis OR two-dimensional polyacrylamide gel electrophoresis)". Related original research articles were included and were carefully analyzed. Eight original proteomic researches on ARDS patients were found. The common proteomic modalities were two-dimensional (2D) high-performance liquid chromatography-based electronic spray ion-MS/MS and 2D-polyacrylamide gel electrophoresis/differential in-gel electrophoresis-based matrix-assisted laser desorption ionization-time of flight/MS. They compared the proteome between ARDS patients and normal controls and analyzed the dynamic changes of proteome at different ARDS stages or severity. The disturbed proteome in ARDS patients includes plasma acute-phase proteins, inflammatory/immune-associated proteins, and coagulation proteins. Although several previous studies have provided some useful information about the lung proteome in ARDS patients and gained several interesting disease-associated biomarkers, clinical proteomic studies in ARDS patients are still in the initial stage. An increased cooperation is still needed to establish a global and faithful database containing disease-specific proteome from the largest ARDS subsets.


Analysis of chromosome 9p21 deletion and p16 gene mutation in salivary gland carcinomas.
The chromosomal locus 9p21 contains the p16(INK4a/CDKN2/MTS1) tumor suppressor gene that has been implicated in a variety of tumor types, including carcinomas of the head and neck, esophagus, and pancreas. To determine whether the loss of this gene is involved in salivary gland cancers, 35 carcinomas and paired nonneoplastic specimens were analyzed for loss of heterozygosity (LOH) of polymorphic genetic markers located in the region of interest. Five types of salivary gland tumors were studied: mucoepidermoid carcinoma, salivary duct carcinoma, adenoid cystic carcinoma, acinic cell carcinoma, and polymorphous low-grade adenocarcinoma. Seven of 9 salivary duct carcinomas showed LOH of 1 or more polymorphic markers. In 1 case of salivary duct carcinoma with LOH, we confirmed a deletion of bp 240-254 within exon 2. In addition, another salivary duct carcinoma showed a homozygous deletion of p16 in differential polymerase chain reaction analysis. Loss of heterozygosity was found in 1 of 10 adenoid cystic carcinomas and 1 of 8 mucoepidermoid carcinomas and was absent in the remaining subtypes. No mutations in exon 1 or exon 2 or homozygous deletion of p16 were found in these 2 particular neoplasms with LOH. These results suggest that inactivation of p16 is important in the development or progression of at least some salivary duct carcinomas, but we found no evidence that its alteration plays a role in the other subtypes examined.


Does personality affect health-related quality of life? A systematic review.
Health-related quality of life (HRQOL) is increasingly measured as an outcome for clinical and health services research. However, relatively little is known about how non-health factors affect HRQOL. Personality is a potentially important factor, yet evidence regarding the effects of personality on HRQOL measures is unclear. This systematic review examined the relationships among aspects of personality and HRQOL. Eligible studies were identified from Medline and PsycINFO. The review included 76 English-language studies with HRQOL as a primary outcome and that assessed personality from the psychological perspective. Individuals with various health states, including ill (e.g., cancer, cardiovascular disorders), aging, and healthy, were included in this review study. Some personality characteristics were consistently related to psychosocial aspects more often than physical aspects of HRQOL. Personality characteristics, especially neuroticism, mastery, optimism, and sense of coherence were most likely to be associated with psychosocial HRQOL. Personality explained varying proportions of variance in different domains of HRQOL. The range of variance explained in psychosocial HRQOL was 0 to 45% and the range of explained variance in physical HRQOL was 0 to 39%. Personality characteristics are related to HRQOL. Systematic collection and analysis of personality data alongside HRQOL measures may be helpful in medical research, clinical practice, and health policy evaluation.


Leukotrienes in asthma. The potential therapeutic role of antileukotriene agents.
Recent advances in research have led to the identification of an inflammatory component to asthma. Although many endogenous mediators are involved in inflammation, leukotrienes appear to play an especially important role in asthma. The leukotrienes produce tissue edema, mucus secretion, and smooth-muscle proliferation, along with a powerful bronchoconstriction. In addition, antileukotriene drugs have emerged as potential therapeutic agents for asthma. This study was designed to review the current information on these new agents. In this review, full-length articles of antileukotriene agents are examined. These articles were found through MEDLINE under the following medical headings: asthma, inflammation, leukotriene, leukotriene-receptor antagonist, and leukotriene-synthesis inhibitor. Most clinical studies cited are placebo-controlled trials involving healthy individuals and patients with asthma. These studies indicate that antileukotriene agents improve lung function and reduce the symptoms of asthma and the need for additional medication. Drugs that inhibit leukotriene-receptor binding and leukotriene synthesis hold promise as new additions to the armamentarium of clinicians who treat asthma. Furthermore, these drugs have already helped to elucidate some details of the pathophysiological features of asthma.


From Signal to Image: Enabling Fine-Grained Gesture Recognition with Commercial Wi-Fi Devices.
Gesture recognition acts as a key enabler for user-friendly human-computer interfaces (HCI). To bridge the human-computer barrier, numerous efforts have been devoted to designing accurate fine-grained gesture recognition systems. Recent advances in wireless sensing hold promise for a ubiquitous, non-invasive and low-cost system with existing Wi-Fi infrastructures. In this paper, we propose DeepNum, which enables fine-grained finger gesture recognition with only a pair of commercial Wi-Fi devices. The key insight of DeepNum is to incorporate the quintessence of deep learning-based image processing so as to better depict the influence induced by subtle finger movements. In particular, we make multiple efforts to transfer sensitive Channel State Information (CSI) into depth radio images, including antenna selection, gesture segmentation and image construction, followed by noisy image purification using high-dimensional relations. To fulfill the restrictive size requirements of deep learning model, we propose a novel region-selection method to constrain the image size and select qualified regions with dominant color and texture features. Finally, a 7-layer Convolutional Neural Network (CNN) and SoftMax function are adopted to achieve automatic feature extraction and accurate gesture classification. Experimental results demonstrate the excellent performance of DeepNum, which recognizes 10 finger gestures with overall accuracy of 98% in three typical indoor scenarios.


RARβ Expression in Keratinocytes from Potentially Malignant Oral Lesions: The Functional Consequences of Re-Expression by De-Methylating Agents.
Loss of RARβ2 expression by promoter methylation is an early event in oral carcinogenesis. Understanding the mechanisms and consequences of RARβ loss may aid in understanding the disappointing results of retinoid chemoprevention trials. This study aimed to describe the effects of all-trans retinoic acid (ATRA) and the de-methylating agent 5-Aza-2' deoxycytidine (5-AZA-CdR) on a panel of immortal potentially malignant oral lesion (PMOL) cell cultures. RARβ expression was assessed in PMOL tissues by immunohistochemistry. Cells were treated with ATRA ± 5-AZA-CdR, and the effects on the cell cycle and senescence were assessed. In PMOL tissues, RARβ expression was variable, but lower in biopsies which gave rise to immortal cell cultures. Treatment of iPMOL cells with ATRA resulted in little change in RARβ expression, but the addition of 5-AZA-CdR resulted in significant increases. The effects on the cell cycle and senescence were variable and may be related to 5-AZA-CdR, as this has wider effects on the cell cycle. Overall, the response of iPMOL cells to ATRA and 5-AZA-CdR treatment was variable and is dependent on several factors, including RARβ-promoter methylation. These findings may help to explain the lack of consistent effect of retinoids in PMOLs seen in chemoprevention trials.


Cancer survivorship: an integral part of Europe's research agenda.
Cancer survivorship has traditionally received little prioritisation and attention. For a long time, the treatment of cancer has been the main focus of healthcare providers' efforts. It is time to increase the amount of attention given to patients' long-term well-being and their ability to return to a productive and good life. This article describes the current state of knowledge and identifies research areas in need of development to enable interventions for improved survivorship for all cancer patients in Europe. The article is summed up with 11 points in need of further focus.


Influence of cholesterol on the collective dynamics of the phospholipid acyl chains in model membranes.
We have studied the packing and collective dynamics of the phospholipid acyl chains in a model membrane composed of 1,2-dimyristoyl-sn-glycero-3-phosphatidylcholine (DMPC) and cholesterol in varied phase state. After a structural characterization of this two-component model bilayer using X-ray reflectivity, we have carried out coherent inelastic neutron scattering to investigate the chain dynamics. Both DMPC/cholesterol membranes exhibited much sharper and more pronounced low-energy inelastic excitations than a pure DMPC membrane. In the high-energy regime above 10 meV, the insertion of cholesterol into the membrane was found to shift the position of the inelastic excitation towards values otherwise found in the pure lipids gel phase. Thus, the dissipative collective short-range dynamics of the acyl chains is strongly influenced by the presence of cholesterol.


Brownian motion in a designer force field: dynamical effects of negative refraction on nanoparticles.
Photonic crystals (PC) have demonstrated unique features that have renewed the fields of classical and quantum optics. Although holding great promises, associated mechanical effects have proven challenging to observe. We demonstrate for the first time that one of the most salient properties of PC, namely negative refraction, can induce specific forces on metal nanoparticles. By integrating a periodically patterned metal film in a fluidic cell, we show that near-field optical forces associated with negatively refracted surface plasmons are capable of controlling particle trajectories. Coupling particle motions to PC band structures draws new approaches and strategies for parallel and high resolution all-optical control of particle flows with applications for micro- and nanofluidic systems.


Conformational changes induced in lens alpha- and gamma-crystallins by modification with glucose 6-phosphate. Implications for cataract.
There is good evidence that the non-enzymic chemical modification of proteins plays a role in the aetiology of cataract and diabetic sequelae. This paper presents new evidence that glycosylation of two major lens structural crystallins, alpha- and gamma-crystallins, by glucose 6-phosphate (G6P) induces conformational changes in the proteins. In addition the surface charge on the molecules is altered. These changes would affect protein-protein and protein-water interactions within the lens and could lead to disruption of the short-range order of the lens proteins which is essential for lens transparency. Conformational changes to lens proteins are known to occur in human cataractous lenses but their cause in vivo is not established. Cumulative chemical modification of proteins, over a period of decades, is a strong candidate as a causal agent.


The role of political affiliation in employment decisions: A model and research agenda.
Organizational researchers have studied how individuals identify with groups and organizations and how this affiliation influences behavior for decades (e.g., Tajfel, 1982). Interestingly, investigation into political affiliation and political affiliation similarity in the organizational sciences is extremely rare. This is striking, given the deep political divides that exist between groups of individuals described in the political science literature. We draw from theories based on similarity, organizational identification, and person-environment fit, as well as theoretical notions related to individuating information, to develop a model, the political affiliation model (PAM), which describes the implications of political affiliation and political similarity for employment decisions. We set forth a number of propositions based on PAM, to spur future research in the organizational sciences for a timely topic which has received little attention. (PsycINFO Database Record


Preaugmentation Soft Tissue Expansion: A Report of Four Pilot Cases.
This pilot study aimed at investigating the safety and feasibility of pre-augmentation soft tissue expansion (STE). Tissue expanders of different sizes (from 240 to 1300 mm3) were implanted subperiosteally in four patients requiring vertical and/or horizontal bone augmentation, and left in situ for 20-60 days, according to the expander size. Guided bone regeneration was carried out after STE completion. Horizontal and vertical bone gains were analyzed through CBCT. Optical scanning and superimposition of cast models were used for volumetric analysis. The mean soft tissue volume increase was 483.8 ± 251.7 mm3. Horizontal bone gain averaged 3 mm in two successfully expanded sites while one case had a vertical bone gain of 8 mm. Despite promising outcomes in bone and soft tissue gain, the present technique needs improvement before being applied routinely in everyday dental practice.


Gut Microbiome Signatures Are Predictive of Infectious Risk Following Induction Therapy for Acute Myeloid Leukemia.
The majority of studies that provide insights into the influence of the microbiome on the health of hematologic malignancy patients have concentrated on the transplant setting. Here, we sought to assess the predictive capacity of the gastrointestinal microbiome and its relationship to infectious outcomes in patients with acute myeloid leukemia (AML). 16s rRNA-based analysis was performed on oral swabs and stool samples obtained biweekly from baseline until neutrophil recovery following induction chemotherapy (IC) in 97 AML patients. Microbiome characteristics were correlated with clinical outcomes both during and after IC completion. At the start of IC, higher stool Shannon diversity (hazard ratio [HR], 0.36; 95% confidence interval [CI], .18-.74) and higher relative abundance of Porphyromonadaceae (HR, 0.36; 95% CI, .18-.73) were associated with increased probability of remaining infection-free during neutropenia. A baseline stool Shannon diversity cutoff of <2 had optimal operating characteristics for predicting infectious complications during neutropenia. Although 56 patients received therapy >72 hours with a carbapenem, none of the patients had an infection with an extended spectrum β-lactamase-producing organism. Patients who received carbapenems for >72 hours had significantly lower α-diversity at neutrophil recovery (P = .001) and were approximately 4 times more likely to have infection in the 90 days following neutrophil recovery (HR, 4.55; 95% CI, 1.73-11.93). Our results suggest that gut microbiome evaluation could assist with infectious risk stratification and that improved targeting of antibiotic administration during IC could decrease subsequent infectious complications in AML patients.Baseline microbiome diversity is a strong independent predictor of infection during acute myeloid leukemia induction chemotherapy (IC) among clinical and microbiome covariates. Higher baseline levels of Porphyromonadaceae appear protective against infection, while carbapenem use is associated with consequences to the microbiome and infection susceptibility post-IC.


Bayesian hierarchically weighted finite mixture models for samples of distributions.
Finite mixtures of Gaussian distributions are known to provide an accurate approximation to any unknown density. Motivated by DNA repair studies in which data are collected for samples of cells from different individuals, we propose a class of hierarchically weighted finite mixture models. The modeling framework incorporates a collection of k Gaussian basis distributions, with the individual-specific response densities expressed as mixtures of these bases. To allow heterogeneity among individuals and predictor effects, we model the mixture weights, while treating the basis distributions as unknown but common to all distributions. This results in a flexible hierarchical model for samples of distributions. We consider analysis of variance-type structures and a parsimonious latent factor representation, which leads to simplified inferences on non-Gaussian covariance structures. Methods for posterior computation are developed, and the model is used to select genetic predictors of baseline DNA damage, susceptibility to induced damage, and rate of repair.


Complement factor H-binding protein of Raji cells and tonsil B lymphocytes.
Several reports have indicated that Factor H has specific effects on certain cell populations, suggesting that Factor H receptors may exist. Lambris & Ross [(1982) J. Exp. Med. 155, 1400-1411] purified a protein from Raji B-lymphoblastoid cell culture supernatants, using Factor H-Sepharose affinity chromatography. This species appeared to consist of two disulphide-linked components each of Mr 50,000, with an additional 50,000-Mr chain attached non-covalently. The existence of cell-surface Factor H-binding proteins has now been re-investigated with 125I surface-labelled Raji and tonsil B cells. Non-ionic-detergent extracts of the cells, in 0.1% Nonidet P40/10 mM-sodium phosphate buffer, pH 7.4, were incubated with Factor H-Sepharose in the presence of proteinase inhibitors. After the beads had been washed, bound components were eluted with 50 mM-NaCl. A single radioactive species was eluted from the resin, which migrates identically with Factor H (apparent Mr 170,000) in SDS/polyacrylamide-gel electrophoresis under reducing and non-reducing conditions. Biosynthetic radiolabelling studies confirmed that this species was synthesized by Raji cells. Examination of culture supernatants from biosynthetically radiolabelled Raji cells showed again the presence of a single soluble species that bound to Factor H-Sepharose, but this species was of lower Mr (approx. 105,000) than the membrane-derived protein. The soluble form may be produced by proteolysis of the membrane form, or may be of separate origin. The similarity in size of the cell-surface protein to Factor H was initially confusing, but it is distinct from cell-surface Factor H on the basis of three criteria: (1) it is not recognized by anti-(Factor H) monoclonal antibodies MRC OX23 and MRC OX24, nor by polyclonal F(ab')2 anti-(Factor H); (2) it does not bind to Zn2+-chelate resin, whereas Factor H does; (3) cell-surface Factor H present on U937 cells does not bind to Factor H-Sepharose.


Reactive capture using metal looping: the effect of oxygen.
In the effort to create a sustainable future economy, the ability to directly convert dilute gas-phase CO2 in waste gas streams into useful products would be a valuable tool, which may be achievable using Grignard reagents as both the capture and the conversion materials. The magnesium salt by-product can be recovered, and metallic magnesium regenerated through conventional high-efficiency electrolysis. This stoichiometric approach is known as metal looping, where the magnesium acts as the energy vector for the capture and conversion, allowing both to occur at room temperature and atmospheric pressure. However, the process has only previously been demonstrated with 12% CO2 in nitrogen mixtures. If we consider this process in a real post-combustion flue gas conversion scenario, the sensitivity of Grignard reagents to other gases (and water vapour) must be considered. While some of these gases and the water vapour are relatively easily removed, in most flue gas streams the most common other gas present, oxygen, would be far more challenging to excise, and oxygen is known to react with Grignard reagents, albeit slowly. In order to determine if higher oxygen concentrations could be tolerated, allowing the possibility of a variety of relatively inexpensive and possibly profitable direct CO2 conversion pathways to be developed, a range of industrially relevant CO2/O2 mixtures were made and carefully bubbled through phenylmagnesium bromide solutions.


Behçet's disease: diagnostic and prognostic aspects of neurological involvement.
This study was conducted to describe clinical and prognostic aspects of neurological involvement in Behçet's disease (BD). Patients referred for neurological evaluation fulfilled the criteria of the International Study Group for Behçet's Disease. We analyzed disability and survival by the Kaplan-Meier method, using Kurtzke's Extended Disability Status Scale (modified for BD) and the prognostic effect of demographic and clinical factors by Cox regression analysis. We studied 164 patients; of the 107 diagnostic neuroimaging studies: 72.1% showed parenchymal involvement, 11.7% venous sinus thrombosis (VST) and the others were normal. CSF studies were performed in 47 patients; all with inflammatory CSF findings (n = 18) had parenchymal involvement. An isolated increase in pressure was compatible with either VST or normal imaging. The final diagnoses were VST (12.2%), neuro-Behçet syndrome (NBS) (75.6%), isolated optic neuritis (0.6%), psycho-Behçet syndrome (0.6%), and indefinite (11%). VST and NBS were never diagnosed together. Ten years from onset of BD 45.1% (all NBS) reached a disability level of EDSS 6 or higher, and 95.7 +/- 2.1% of the patients were still alive. Having accompanying cerebellar symptoms at onset or a progressive course is unfavorable. Onset with headache or a diagnosis of VST is favorable. Two major neurological diagnoses in BD are NBS and VST. These are distinct in clinical, radiological, and prognostic aspects, hence suggesting a difference in pathogenesis.


Incidence and recurrence rate of placental abruption: a longitudinal linked national cohort study in the Netherlands.
Women who have experienced a placental abruption have a risk of recurrence, but exact information to quantify this risk is currently not available. We studied the incidence and recurrence rate of placental abruption in a subsequent pregnancy and the influence of hypertensive disorders. We conducted a retrospective national cohort study of all singleton pregnancies that ended from 1999-2007 in the Netherlands. A longitudinal linked national cohort of these women with information on a subsequent singleton delivery was used. We calculated and compared incidence and recurrence rates of placental abruption for women in total, stratified by gestational age of first placental abruption and by the presence of a hypertensive disorder in their first pregnancy. We studied 1,570,635 women of which 3496 (0.22%) experienced a placental abruption. Information was available on a subsequent singleton delivery for 264,424 deliveries. Of these, 521 women (0.20%) had a placental abruption in the first pregnancy vs 214 women (0.08%) in the second pregnancy. The risk of placental abruption in a subsequent pregnancy was significantly higher in women with a previous placental abruption compared with women without (5.8% vs 0.06%; adjusted odds ratio [aOR], 93; 95% confidence interval [CI], 62-139). Women with a placental abruption that occurred at term in their first pregnancy were more at risk for recurrence (aOR, 188; 95% CI, 116-306) than women with a preterm (aOR, 52; 95% CI, 25-111) or early preterm (<32 weeks of gestation) placental abruption in their first pregnancy (aOR, 39; 95% CI, 13-116). Placental abruption was more frequent among women with a hypertensive disorder compared with normotensive women (0.44% vs 0.16%; odds ratio, 2.7; 95% CI, 2.3-3.3). Women with a hypertensive disorder were less at risk for recurrence than were normotensive women (aOR, 0.68; 95% CI, 0.27-1.6). No interaction between a hypertensive disorder in the first pregnancy and the recurrence risk was found. Women with a placental abruption in their first pregnancy have a greatly increased risk of placental abruption in a subsequent pregnancy. Hypertensive disorders increase the risk of placental abruption but do not increase the recurrence rate in a subsequent pregnancy. We suggest elective induction from 37 weeks of gestation for women with a history of placental abruption at term in a previous pregnancy.


Obstetrical results after embryonic reductions performed on 34 multiple pregnancies.
Thirty-four women with multiple pregnancies (three or more fetuses) underwent embryonic reduction in order to reduce abortions, premature births or fetal growth-retardation by obtention of twins. Four early abortions occurred. Thirty pregnancies reached term and out of 60 fetuses, 58 infants were born alive. Fetal death in utero of one twin occurred in two pregnancies. The mean term until delivery was 36 +/- 2.8 weeks gestation and the prematurity rate was 51.7%. Of 55 neonates, 25 were underweight within the 10th percentile and 10 out of 55 neonates were underweight below the 3rd percentile. There were three deaths in the early neonatal period. The rate of perinatal mortality was 8.3%. Fifty-four children are currently healthy and one child has a mild axial hypotonia. A reduction in prematurity was observed with a gain of 2 weeks on reported data concerning triplet pregnancies. The rate of low-birth-weight infants was high, 63.5% being underweight at birth.


Stereotactic body radiotherapy for oligometastatic breast cancer: a new standard of care, or a medical reversal in waiting?
Metastases-directed therapy via surgery or stereotactic body radiotherapy (SBRT) has become the de facto standard of care in the United States and abroad despite a lack of high quality prospective, randomized trials. Oligometastatic tumors may behave in an inherently more indolent manner secondary to underlying biologic characteristics, including discrepant microRNA expression patterns. This biologic discrepancy suggests that historic improvements in survival observed in retrospective series may stem from the inherent biology of oligometastases and selection biases as opposed to advances in novel localized treatments. In this review, we discuss the theoretical basis for metastases-directed therapies, retrospective data supporting these approaches, recent advances in oligometastasis biology, and ongoing prospective randomized trials designed to compare SBRT and standard of care systemic therapies. We focus on metastases-directed therapy, primarily SBRT, for oligometastatic breast cancer with references to other tumor types when these other tumor types inform oligometastatic breast cancer treatment.