ReacNetGenerator: an automatic reaction network generator for reactive molecular dynamics simulations.
Reactive molecular dynamics (MD) simulation makes it possible to study the reaction mechanism of complex reaction systems at the atomic level. However, the analysis of MD trajectories which contain thousands of species and reaction pathways has become a major obstacle to the application of reactive MD simulation in large-scale systems. Here, we report the development and application of the Reaction Network Generator (ReacNetGenerator) method. It can automatically extract the reaction network from the reaction trajectory without any predefined reaction coordinates and elementary reaction steps. Molecular species can be automatically identified from the cartesian coordinates of atoms and the hidden Markov model is used to filter the trajectory noises which makes the analysis process easier and more accurate. The ReacNetGenerator has been successfully used to analyze the reactive MD trajectories of the combustion of methane and 4-component surrogate fuel for rocket propellant 3 (RP-3), and it has great advantages in terms of efficiency and accuracy compared to traditional manual analysis.


Allergen immunotherapy with nanoparticles containing lipopolysaccharide from Brucella ovis.
The adjuvant and protective capacity against anaphylactic shock of the association between rough lipopolysaccharide of Brucella ovis (LPS) coencapsulated with ovalbumin (OVA), as a model allergen, in Gantrez AN nanoparticles was investigated. Several strategies were performed in order to study the adjuvant effect of the LPS either encapsulated or coating the nanoparticles. OVA, as well as LPS, was incorporated either during the manufacturing process (OVA-encapsulated or LPS-encapsulated nanoparticles, respectively) or after the preparation (OVA-coated or LPS-coated nanoparticles, respectively). After the administration of 10 microg of OVA incorporated in the different formulations, all the nanoparticles, with or without LPS, were capable of amplifying the immune response (IgG(1) and IgG(2a)). However, in a model of sensitized mice to OVA, the formulation with OVA and LPS-entrapped inside the nanoparticles administered intradermally in three doses of 3 microg of OVA each was the only treatment that totally protected the mice from death after a challenge with an intraperitoneal injection of OVA. In contrast, the control group administered with OVA adsorbed onto a commercial alhydrogel adjuvant showed 80% mortality. These results are highly suggestive for the valuable use of Gantrez nanoparticles combined with rough LPS of B. ovis in immunotherapy.


The assessment of medical technologist. Examples from Switzerland.
The need for assessment of new medical technologies has recently become evident in many countries, especially for the people responsible for health care policy. There are multiple reasons for making evaluation: rising costs in health care, medical efficacy, safety, as well as social and political issues. Each stage of life of a diagnostic, therapeutic or preventive technology, from its emergence to obsolescence, can be assessed by an appropriate procedure. In Switzerland, a country with decentralized health care as well as political systems, the assessment is made by various institutions. Evaluative aspects are included in some National Research Foundation programs. Most work, however, is done by the division of medical techniques at the Swiss Hospital Institute. The panel of experts has recently prepared a report on magnetic resonance imaging (MRI). As a result of the initial evaluation, the need for this new technology in this country, and the number and sites of MRI systems for the next few years were established. The capital, running and unitary costs of this diagnostic procedure were estimated. The report will be of aid to the people planning investments and dealing with questions of reimbursement and other issues of health care policy. The methods of epidemiology, biostatistics, sociology and health economics used by the institutes of social and preventive medicine are very helpful in the procedures of technology assessment.


Fingertip replantations: clinical evaluation of 135 digits.
From July 1985 to February 1993, 135 digits in 119 patients with complete amputations at or distal to the distal interphalangeal joint (zone I for amputations distal to the nail base of zone II for amputations between the distal interphalangeal joint and the nail base) were replanted using a microsurgical technique at Korea University Guro Hospital. Because of the high social value placed on body form and function, the indication for replantation was extended to cases with severe soft-tissue injuries and attempted replantation as a routine procedure in nearly all distal amputation cases. The overall survival rate was 78 percent, with the survival rate for zone I being 70 percent and that for zone II reaching 86 percent. Even in cases with severe soft-tissue injury, the survival rate was high, with viability in avulsion injuries and crush injuries reaching 75 percent each. The most common type of vascular repair in zone I cases was revascularization of one artery only and no vein repair (87 percent). Of these cases, interpositional vein grafts were used in 65 percent. In zone II cases, the most common combination repair was one artery and one vein anastomosis (70 percent), with interpositional vein grafts for arterial anastomosis in 49 percent; most of the venous repair was feasible by the direct method (78 percent). The follow-up period ranged from 1 month to 5 years with a mean of 14.8 months; 52 patients were followed-up for more than 6 months. In 52 long-term follow-up patients, the average two-point discrimination was 8 mm. Patient satisfaction, aesthetically and functionally, was high (91 percent).


Therapy of severe diabetic ketoacidosis. Zero-mortality under very-low-dose insulin application.
Despite modern concepts in therapy by low-dose insulin application and better care in intensive care units (ICUs), there still is a mortality of 5-10% for severe diabetic ketoacidosis (DKA). The aim of this study was to develop a therapy concept to reduce complications and mortality in DKA. From 1986 to 1997, 114 consecutive patients (mean [range]; age 34 [11-74] years) with type 1 diabetes suffering from severe DKA were treated on ICUs and investigated in a retrospective and prospective study. The following are the criteria for admission onto ICUs: < 7.20 pH level, > 300 mg/dl blood glucose, less than -12 mmol/l base excess, or < 300 mg/dl blood glucose plus severe symptoms (i.e., coma). We treated patients according to the following concepts: very-low-dose insulin application by a basal insulin infusion of 1 U/h (0.5-4.0 U/h i.v.), maximal decrease of blood glucose level by 50 mg. dl-1. h-1, slow-motion reequilibration by fluid substitution of 1,000 ml/h (Ringer-Lactate, NaCl 0.9% or half-electrolyte fluids) in the first 4 h, potassium replacement and heparin (500-1,000 U/h i.v.). When patients were admitted to ICU, we found the following parameters: mean (range); 609.0 (86.0-1,428.0) mg/dl blood glucose level; 7.13 (6.53-7.36) pH level; and -19.7 (-41.2 to -7.0) mmol/l base excess. After 12 h of treatment, we reached the following parameters: mean values; 251 mg/dl blood glucose level, 7.31 pH level, and -9.37 mmol/l base excess level. All patients survived without any lasting deficiencies or fatal complications. Very-low-dose insulin application and slow-motion reequilibration plus monitored substitution of electrolytes are the basic strategies in the treatment of severe DKA. In our view, small doses of infused insulin are the main reason for the safe results of this therapy program.


An ultrastructural study of alkaline phosphatase in a transplantable rat osteogenic sarcoma.
Alkaline phosphatase (AP) has been demonstrated by combined electron microscopy and histochemistry in a transplantable rat osteogenic sarcoma, using a modified Gomori technique (Salomon, 1974). During the early stages of growth of subcutaneously implanted tumors, AP was detected in intracellular membrane systems resembling Golgi and on membranes of cells and matrix vesicles. During growth of the tumor, there was extensive development of intercellular collagen, and AP was demonstrated in bodies associated with collagen. In some cases the AP-containing bodies resembled matrix vesicles, but there was considerable size heterogeneity of the AP-containing bodies, suggesting that there may be heterogeneity of matrix vesicles. The amount of detectable AP seemed to increase in all areas of the tumor which were viable, during tumor growth, but no AP could be detected in cell debris of necrotic areas of the tumor (area C) nor associated with collagen in that area. Area D, particularly during later stages of tumor growth, showed the greatest development of calcium deposits, with calcium spicules apparently associated with AP-containing bodies on both cell membranes and collagen. AP-containing bodies also appeared in large numbers in venules during later stages of tumor growth, associated with an amorphous material. This may account for the increase in serum AP activity which occurs during later stages of growth of transplanted tumors. The sites of AP activity in this osteogenic sarcoma were similar to those described in normal tissue, but generally seemed to be more abundant.


Lifespan adversity and later adulthood telomere length in the nationally representative US Health and Retirement Study.
Stress over the lifespan is thought to promote accelerated aging and early disease. Telomere length is a marker of cell aging that appears to be one mediator of this relationship. Telomere length is associated with early adversity and with chronic stressors in adulthood in many studies. Although cumulative lifespan adversity should have bigger impacts than single events, it is also possible that adversity in childhood has larger effects on later life health than adult stressors, as suggested by models of biological embedding in early life. No studies have examined the individual vs. cumulative effects of childhood and adulthood adversities on adult telomere length. Here, we examined the relationship between cumulative childhood and adulthood adversity, adding up a range of severe financial, traumatic, and social exposures, as well as comparing them to each other, in relation to salivary telomere length. We examined 4,598 men and women from the US Health and Retirement Study. Single adversities tended to have nonsignificant relations with telomere length. In adjusted models, lifetime cumulative adversity predicted 6% greater odds of shorter telomere length. This result was mainly due to childhood adversity. In adjusted models for cumulative childhood adversity, the occurrence of each additional childhood event predicted 11% increased odds of having short telomeres. This result appeared mainly because of social/traumatic exposures rather than financial exposures. This study suggests that the shadow of childhood adversity may reach far into later adulthood in part through cellular aging.


The association between baseline vitamin E, selenium, and prostate cancer in the alpha-tocopherol, beta-carotene cancer prevention study.
The association between prostate cancer and baseline vitamin E and selenium was evaluated in the trial-based cohort of the Alpha-Tocopherol, Beta-Carotene Cancer Prevention Study (n = 29,133). During up to 9 years of follow-up, 317 men developed incident prostate cancer. Multivariate Cox proportional hazards models that adjusted for intervention group, benign prostatic hyperplasia, age, smoking, and urban residence were used to evaluate associations between prostate cancer and exposures of interest. There were no significant associations between baseline serum alpha-tocopherol, dietary vitamin E, or selenium and prostate cancer overall. The associations between prostate cancer and vitamin E and some of the baseline dietary tocopherols differed significantly by alpha-tocopherol intervention status, with the suggestion of a protective effect for total vitamin E among those who received the alpha-tocopherol intervention (relative risk was 1.00, 0.68, 0.80, and 0.52 for increasing quartiles; P = 0.07).


Analysis of a photoacoustic imaging system by the crosstalk matrix and singular value decomposition.
Photoacoustic imaging is a hybrid imaging modality capable of producing contrast similar to optical imaging techniques but with increased penetration depth and resolution in turbid media by encoding the information as acoustic waves. In general, it is important to characterize the performance of a photoacoustic imaging system by parameters such as sensitivity, resolution, and contrast. However, system characterization can extend beyond these metrics by implementing advanced analysis via the crosstalk matrix and singular value decomposition. A method was developed to experimentally measure a matrix that represented the imaging operator for a photoacoustic imaging system. Computations to produce the crosstalk matrix were completed to provide insight into the spatially dependent sensitivity and aliasing for the photoacoustic imaging system. Further analysis of the imaging operator was done via singular value decomposition to estimate the capability of the imaging system to reconstruct objects and the inherent sensitivity to those objects. The results provided by singular value decomposition were compared to SVD results from a de-noised imaging operator to estimate the number of measurable singular vectors for the system. These characterization techniques can be broadly applied to any photoacoustic system and, with regards to the studied system, could be used as a basis for improvements to future iterations.


Obsessions and compulsions in women with postpartum depression.
The quantity, content, and intensity of the obsessions and compulsions of women with postpartum onset major depressive disorder were compared with those of women with major depressive disorder with non-postpartum onset. Sequential cases of women with postpartum onset major depression (N = 37) and major depression (N = 28) who presented to our Women's Mood Disorders program were included. Psychiatric examination using DSM-IV criteria and the Inventory to Diagnose Depression established the diagnosis of major depression. Obsessive thoughts and compulsions were reported on the Yale-Brown Obsessive Compulsive Scale and reviewed during the psychiatric examination. Comparisons between groups were performed with chi-square statistics, Fisher exact test and its extensions, and Mann-Whitney U test. Although more women with postpartum onset major depression (N = 21, 57%) than major depression (N = 10, 36%) reported obsessional thoughts, the difference between the groups was not significant (p = .13). However, for women who endorsed obsessions, those with postpartum onset had a higher median number (median = 7) than women without postpartum onset (median = 2, p = .00). Most of the difference in frequency of thoughts was owing to more women with postpartum onset major depression having aggressive thoughts (N = 20, 95%) than women with major depression (N = 6, 60%, Fisher exact p = .03). The most frequent content of the aggressive thoughts for women with postpartum onset major depression was causing harm to their newborns or infants. The presence or number of obsessional thoughts or compulsions was not related to severity of the depressive episode. Childbearing-aged women commonly experience obsessional thoughts or compulsions in the context of major depressive episodes. Women with postpartum onset major depression experience disturbing aggressive obsessional thoughts more frequently than women with non-postpartum major depression.


Genetic and morphological divergences in the cosmopolitan deep-sea amphipod Eurythenes gryllus reveal a diverse abyss and a bipolar species.
Eurythenes gryllus is one of the most widespread amphipod species, occurring in every ocean with a depth range covering the bathyal, abyssal and hadal zones. Previous studies, however, indicated the existence of several genetically and morphologically divergent lineages, questioning the assumption of its cosmopolitan and eurybathic distribution. For the first time, its genetic diversity was explored at the global scale (Arctic, Atlantic, Pacific and Southern oceans) by analyzing nuclear (28S rDNA) and mitochondrial (COI, 16S rDNA) sequence data using various species delimitation methods in a phylogeographic context. Nine putative species-level clades were identified within E. gryllus. A clear distinction was observed between samples collected at bathyal versus abyssal depths, with a genetic break occurring around 3,000 m. Two bathyal and two abyssal lineages showed a widespread distribution, while five other abyssal lineages each seemed to be restricted to a single ocean basin. The observed higher diversity in the abyss compared to the bathyal zone stands in contrast to the depth-differentiation hypothesis. Our results indicate that, despite the more uniform environment of the abyss and its presumed lack of obvious isolating barriers, abyssal populations might be more likely to show population differentiation and undergo speciation events than previously assumed. Potential factors influencing species' origins and distributions, such as hydrostatic pressure, are discussed. In addition, morphological findings coincided with the molecular clades. Of all specimens available for examination, those of the bipolar bathyal clade seemed the most similar to the 'true' E. gryllus. We present the first molecular evidence for a bipolar distribution in a macro-benthic deep-sea organism.


Catastrophic health expenditure of Vietnamese patients with gallstone diseases - a case for health insurance policy revaluation.
Despite gallstone diseases (GSDs) being a major public health concern with both acute and chronic episodes, none of the studies in Vietnam has been conducted to investigate the household expenditure for the GSD treatment. The objective of this study was to estimate the costs of managing GSD and to explore the prevalence and determinants of catastrophic health expenditure (CHE) among Vietnamese patients. A cross-sectional study was conducted from June 2016 to March 2017 in the Department of Hepatobiliary and Pancreatic Surgery, Viet Duc Hospital in Hanoi, Vietnam. A total of 206 patients were enrolled. Demographic and socioeconomic data, household income, and direct and indirect medical costs of patients seeking treatment for GSD were collected through face-to-face interview. Multivariate logistic regression was used to explore factors associated with CHE. The prevalence of CHE in patients suffering from GSD was 35%. The percentage of patients who were covered by health insurance and at risk for CHE was 41.2%, significantly higher than that of those noninsured (15.8%). Proportions of patients with and without health insurance who sought outpatient treatment were 30.6% and 81.6%, respectively. Patients who were divorced or widowed and had intrahepatic gallstones were significantly more likely to experience CHE. Those who were outpatients, were women, had history of pharmacological treatment to parasitic infection, and belong to middle and highest monthly household income quantile were significantly less likely to experience CHE. The findings suggested that efforts to re-evaluate health insurance reimbursement capacity, especially for acute diseases and taking into account the varying preferences of people with different disease severity, should be conducted by health authority. Further studies concerning CHE of GSD in the context of ongoing health policy reform should consider utilizing WHO-recommended measures like the fairness in financial contribution index, as well as taking into consideration the behavioral aspects of health care spending.


Modulation of the DNA-damage response to HZE particles by shielding.
Ions of high atomic number and energy (HZE particles) pose a significant cancer risk to astronauts on prolonged space missions. On Earth, similar ions are being used for targeted cancer therapy. The properties of these particles can be drastically altered during passage through spacecraft shielding, therapy beam modulators, or the human body. Here, we have used pertinent responses to DNA double-strand breaks (DSBs) to understand the consequences of energy loss versus nuclear fragmentation of Fe ions during passage through shielding or tissue-equivalent materials. Phosphorylation of histone H2AX and recruitment of 53BP1 were used to generate 3D reconstructions of DNA damage in human cells and to follow its repair. Human cells are unable to repair a significant portion of DNA damage induced by Fe ions. DNA-PK and ATM are required, to different extents, for the partial repair of Fe-induced DNA damage. Aluminum shielding has little effect on DNA damage or its repair, confirming that the hulls of the Space Shuttle and the International Space Station afford scant protection against these particles. Lead shielding, on the other hand, exacerbates the effects of Fe ions due to energy loss during particle traversal. In sharp contrast, polyethylene (PE), a favored hydrogenous shield, results in DNA damage that is more amenable to repair presumably due to Fe-ion fragmentation. Human cells are indeed able to efficiently repair DSBs induced by chlorine ions and protons that represent fragmentation products of Fe. Interestingly, activation of the tumor suppressor p53 in Fe-irradiated cells is uniquely biphasic and culminates in the induction of high levels of p21 (Waf1/Cip1), p16 (INK4a) and senescence-associated beta-galactosidase activity. Surprisingly, these events occur even in the absence of ATM kinase implying that ATR may be a major responder to the complex DNA damage inflicted by Fe ions. Significantly, fragmentation of the Fe beam through PE attenuates these responses and this, in turn, results in better long-term survival in a colony-forming assay. Our results help us to understand the biological consequences of ion fragmentation through materials, whether in space or in the clinic, and provide us with a biological basis for the use of hydrogenous materials like PE as effective space shields.


Inhibition of diabetic nephropathy by a decoy peptide corresponding to the "handle" region for nonproteolytic activation of prorenin.
We found that when a site-specific binding protein interacts with the "handle" region of the prorenin prosegment, the prorenin molecule undergoes a conformational change to its enzymatically active state. This nonproteolytic activation is completely blocked by a decoy peptide with the handle region structure, which competitively binds to such a binding protein. Given increased plasma prorenin in diabetes, we examined the hypothesis that the nonproteolytic activation of prorenin plays a significant role in diabetic organ damage. Streptozotocin-induced diabetic rats were treated with subcutaneous administration of handle region peptide. Metabolic and renal histological changes and the renin-Ang system components in the plasma and kidneys were determined at 8, 16, and 24 weeks following streptozotocin treatment. Kidneys of diabetic rats contained increased Ang I and II without any changes in renin, Ang-converting enzyme, or angiotensinogen synthesis. Treatment with the handle region peptide decreased the renal content of Ang I and II, however, and completely inhibited the development of diabetic nephropathy without affecting hyperglycemia. We propose that the nonproteolytic activation of prorenin may be a significant mechanism of diabetic nephropathy. The mechanism and substances causing nonproteolytic activation of prorenin may serve as important therapeutic targets for the prevention of diabetic organ damage.


B lymphocytes in neuromyelitis optica.
Neuromyelitis optica (NMO) is an inflammatory autoimmune disorder of the CNS that predominantly affects the spinal cord and optic nerves. A majority (approximately 75%) of patients with NMO are seropositive for autoantibodies against the astrocyte water channel aquaporin-4 (AQP4). These autoantibodies are predominantly IgG1, and considerable evidence supports their pathogenicity, presumably by binding to AQP4 on CNS astrocytes, resulting in astrocyte injury and inflammation. Convergent clinical and laboratory-based investigations have indicated that B cells play a fundamental role in NMO immunopathology. Multiple mechanisms have been hypothesized: AQP4 autoantibody production, enhanced proinflammatory B cell and plasmablast activity, aberrant B cell tolerance checkpoints, diminished B cell regulatory function, and loss of B cell anergy. Accordingly, many current off-label therapies for NMO deplete B cells or modulate their activity. Understanding the role and mechanisms whereby B cells contribute to initiation, maintenance, and propagation of disease activity is important to advancing our understanding of NMO pathogenesis and developing effective disease-specific therapies.


The impact of continuously-variable dose rate VMAT on beam stability, MLC positioning, and overall plan dosimetry.
A recent control system update for Elekta linear accelerators includes the ability to deliver volumetric-modulated arc therapy (VMAT) with continuously variable dose rate (CVDR), rather than a number of fixed binned dose rates (BDR). The capacity to select from a larger range of dose rates allows the linac to maintain higher gantry speeds, resulting in faster, smoother deliveries. The purpose of this study is to investigate two components of CVDR delivery - the increase in average dose rate and gantry speed, and a determination of their effects on beam stability, MLC positioning, and overall plan dosimetry. Initially, ten VMAT plans (5 prostate, 5head and neck) were delivered to a Delta4 dosimetric phantom using both the BDR and CVDR systems. The plans were found to be dosimetrically robust using both delivery methods, although CVDR was observed to give higher gamma pass rates at the 2%/2 mm gamma level for prostates (p < 0.01). For the dual arc head-and-neck plans, CVDR delivery resulted in improved pass rates at all gamma levels (2%/2 mm to 4%/4 mm) for individual arc verifications (p < 0.01), but gave similar results to BDR when both arcs were combined. To investigate the impact of increased gantry speed on MLC positioning, a dynamic leaf-tracking tool was developed using the electronic portal imaging device (EPID). Comparing the detected MLC positions to those expected from the plan, CVDR was observed to result in a larger mean error compared to BDR (0.13 cm and 0.06 cm, respectively, p < 0.01). The EPID images were also used to monitor beam stability during delivery. It was found that the CVDR deliveries had a lower standard deviation of the gun-target (GT) and transverse (AB) profiles (p < 0.01). This study has determined that CVDR may offer a dosimetric advantage for VMAT plans. While the higher gantry speed of CVDR appears to increase deviations in MLC positioning, the relative effect on dosimetry is lower than the positive impact of a flatter and more stable beam profile.


Sheep rumen and omasum primary cultures and source epithelia: barrier function aligns with expression of tight junction proteins.
The forestomachs of cows and sheep have historically served as important models for the study of epithelial transport. Thus, the ruminal epithelium was among the first tissues in which absorption of chloride against an electrochemical gradient was observed, requiring a tight paracellular barrier to prevent back-leakage. However, little is known about ruminal barrier function, despite the considerable implications for ruminant health. The tight junction proteins of the omasum have never been investigated, and no cell culture model exists. We present a new method for the isolation of cells from forestomach epithelia. Protein expression of cells and source tissues of sheep were studied using western blot, PCR and confocal laser scanning microscopy. Cultured cells were characterized by transepithelial resistance (TER) measurements and patch clamping. Cells developed TER values of 729±134 Ω cm(2) (rumen) and 1522±126 Ω cm(2) (omasum). Both primary cells and source epithelia of rumen and omasum expressed cytokeratin, occludin and claudins 1, 4 and 7 (but not claudins 2, 3, 5, 8 and 10), consistent with the observed paracellular sealing properties. Staining for claudin-1 reached the stratum basale. The full mRNA coding sequence of claudins 1, 4 and 7 (sheep) was obtained. Patch-clamp analyses of isolated cells proved expression of an anion conductance with a permeability sequence of gluconate<acetate<chloride. This is in accordance with a model that ruminal and omasal transport of anions such as chloride and acetate has to occur via a transcellular route and involves channel-mediated basolateral efflux, driven by Na(+)/K(+)-ATPase.


Barriers and enablers to walking in individuals with intermittent claudication: A systematic review to conceptualize a relevant and patient-centered program.
Walking limitation in patients with peripheral arterial disease (PAD) and intermittent claudication (IC) contributes to poorer disease outcomes. Identifying and examining barriers to walking may be an important step in developing a comprehensive patient-centered self-management intervention to promote walking in this population. To systematically review the literature regarding barriers and enablers to walking exercise in individuals with IC. A systematic review was conducted utilizing integrative review methodology. Five electronic databases and the reference lists of relevant studies were searched. Findings were categorized into personal, walking activity related, and environmental barriers and enablers using a social cognitive framework. Eighteen studies including quantitative (n = 12), qualitative (n = 5), and mixed method (n = 1) designs, and reporting data from a total of 4376 patients with IC, were included in the review. The most frequently reported barriers to engaging in walking were comorbid health concerns, walking induced pain, lack of knowledge (e.g. about the disease pathology and walking recommendations), and poor walking capacity. The most frequently reported enablers were cognitive coping strategies, good support systems, and receiving specific instructions to walk. Findings suggest additionally that wider behavioral and environmental obstacles should be addressed in a patient-centered self-management intervention. This review has identified multidimensional factors influencing walking in patients with IC. Within the social cognitive framework, these factors fall within patient level factors (e.g. comorbid health concerns), walking related factors (e.g. claudication pain), and environmental factors (e.g. support systems). These factors are worth considering when developing self-management interventions to increase walking in patients with IC. Systematic review registration CRD42018070418.


Bronchial eosinophilic infiltration in Crohn's disease in the absence of pulmonary disease.
Immunological and functional bronchopulmonary abnormalities may be present in up to two-thirds of patients with Crohn's disease. Having recently described a mild increase in methacholine airways responsiveness in these patients, we investigated whether this physiological abnormality is associated with bronchial inflammation since it has previously been described in asthma. Eighteen patients with Crohn's disease and 15 healthy controls matched for age, atopy and smoking habit, were studied. All the subjects underwent a bronchial methacholine challenge (1, 4 and 16 mg/mL) and a sputum induction by inhalation of hypertonic saline (NaCl 4.5%). The sputum samples were analysed for their cellular composition as well as for the levels of several mediators and proteins in the fluid phase, including eosinophil cationic protein (ECP), myeloperoxydase, albumin, alpha2-macroglobulin, interleukin-8 (IL-8), IgA and IL-8/immunoglobulin A complexes. When compared to control subjects, patients with Crohn's disease had significantly higher sputum eosinophil counts (14.5% [0-79.9%] vs 0.2% [0-2.3%]; P < 0. 001) and ECP levels (26.2 microg/L [4-124.2 microg/L] vs 9.8 microg/L [0-94.2 microg/L]; P < 0.05). However, patients with Crohn's disease had no sign of increased plasma exudation as reflected by sputum levels of albumin and alpha2-macroglobulin similar to those seen in control subjects. Furthermore the sputum levels of IL-8, IgA and IL-8/IgA complexes were not significantly different between the two groups. The magnitude of the fall in forced expiratory volume in 1 s after methacholine inhalation was significantly increased in Crohn's disease patients although it did not correlate with the extent of sputum eosinophilia or with the sputum ECP levels. Crohn's disease patients without any clinical respiratory involvement have airway eosinophilia without local increased plasma exudation. However, bronchial eosinophilia in Crohn's disease per se is not sufficient to induce clinically significant airway hyperresponsiveness, suggesting that other factors than bronchial eosinophilic infiltration are required for the clinical expression of an airway instability.


US FDA outreach to the regenerative medicine community: challenges and opportunities.
Advances in the field of regenerative medicine have yielded novel approaches to developing treatments for currently unmet medical needs. The regenerative medicine field is diverse, spanning many research and clinical disciplines; no single society or organization fully represents regenerative medicine. The US FDA maintains an active dialog with a variety of stakeholders to keep abreast of the latest available science, to anticipate regulatory challenges posed by the latest scientific developments and to educate stakeholders about regulatory expectations for product development. The diversity of stakeholders in this field makes this dialog challenging. This article provides an overview of some of the FDA's current outreach activities in this area. The FDA welcomes opportunities to enhance its interactions with the regenerative medicine community.


The high resolution melting analysis (HRM) as a molecular tool for monitoring parasites of the wildlife.
In an interconnected world, the international pet trade on wild animals is becoming increasingly important. As a consequence, non-native parasite species are introduced, which affect the health of wildlife and contribute to the loss of biodiversity. Because the investigation of parasite diversity within vulnerable host species implies the molecular identification of large samples of parasite eggs, the sequencing of DNA barcodes is time-consuming and costly. Thereby, the objectives of our study were to apply the high resolution melting (HRM) approach for species determination from pools of parasite eggs. Molecular assays were validated on flatworm parasites (polystomes) infecting the Mediterranean pond turtle Mauremys leprosa and the invasive red-eared slider Trachemys scripta elegans in French natural environments. HRM analysis results indicated that double or multiple parasitic infections could be detected from wild animal populations. They also showed that the cycle of parasite eggs production was not regular over time and may depend on several factors, among which the ecological niche and the target species. Thereby, monitoring parasites from wild endangered animals implies periodic parasitological surveys to avoid false negative diagnostics, based solely on eggs production.


Synthesis, structure and luminescence properties of new chloro-germanate phosphors Ca₃GeO₄Cl₂:Eu²⁺.
A kind of novel blue-emitting chloro-germanate phosphor Ca3GeO4Cl2:Eu(2+) has been synthesized via a high temperature solid-state method. The crystal structure of the as-prepared phosphor was discussed from the viewpoint of the doping behaviors of the activators. The luminescence properties and thermal stability of Ca3GeO4Cl2:Eu(2+) was investigated in detail. Ca3GeO4Cl2:Eu(2+) phosphors exhibit a broad-band excitation band in the near ultra-violet region and a blue emission peak at 428 nm, which are both ascribed to the 4f-5d transitions of the Eu(2+) ions. The optimum concentration of Eu(2+) in the Ca3GeO4Cl2 phosphor was determined to be 3 mol%, and the concentration quenching mechanism was considered to be the dipole-dipole interaction with a critical distance of R(c) = 22.11 Å. Thermal stability studies show that the photoluminescence intensity of the Ca3GeO4Cl2:Eu(2+) phosphor at 150 °C was 77% of the initial value at room temperature. The activation energy, E, was calculated to be 0.163 eV suggesting good thermal stability. The variation in lifetime of Ca3GeO4Cl2:Eu(2+) phosphor was also discussed to verify different luminescence centers in the lattice.


The cell's view of animal body-plan evolution.
An adult animal's form is shaped by the collective behavior of cells during embryonic development. To understand the forces that drove the divergence of animal body-plans, evolutionary developmental biology has focused largely on studying genetic networks operating during development. However, it is less well understood how these networks modulate characteristics at the cellular level, such as the shape, polarity, or migration of cells. We organized the "Cell's view of animal body plan evolution" symposium for the 2014 The Society for Integrative and Comparative Biology meeting with the explicit goal of bringing together researchers studying the cell biology of embryonic development in diverse animal taxa. Using a broad range of established and emerging technologies, including live imaging, single-cell analysis, and mathematical modeling, symposium participants revealed mechanisms underlying cells' behavior, a few of which we highlight here. Shape, adhesion, and movements of cells can be modulated over the course of evolution to alter adult body-plans and a major theme explored during the symposium was the role of actomyosin in coordinating diverse behaviors of cells underlying morphogenesis in a myriad of contexts. Uncovering whether conserved or divergent genetic mechanisms guide the contractility of actomyosin in these systems will be crucial to understanding the evolution of the body-plans of animals from a cellular perspective. Many speakers presented research describing developmental phenomena in which cell division and tissue growth can control the form of the adult, and other presenters shared work on studying cell-fate specification, an important source of novelty in animal body-plans. Participants also presented studies of regeneration in annelids, flatworms, acoels, and cnidarians, and provided a unifying view of the regulation of cellular behavior during different life-history stages. Additionally, several presentations highlighted technological advances that glean mechanistic insights from new and emerging model systems, thereby providing the phylogenetic breadth so essential for studying animal evolution. Thus, we propose that an explicit study of cellular phenomena is now possible for a wide range of taxa, and that it will be highly informative for understanding the evolution of animal body-plans.


Characterization of amyloid-β granules in the hippocampus of SAMP8 mice.
The senescence accelerated mouse-prone 8 (SAMP8) strain of mice is an experimental model of accelerated senescence that has also been proposed as a model of Alzheimer's disease as it shares several features with this dementia. We have recently reported amyloid-β (Aβ) granules in the hippocampus of SAMP8 mice, which contain Aβ42 and Aβ40 peptides and other amyloid-β protein precursor fragments. These granules appear clustered mainly in the stratum radiatum of the CA1 region and increase in number and size with age. Here we performed several studies to examine whether the Aβ granules in the hippocampus of SAMP8 mice contain other proteins characteristic of neuropathological aggregates, such as tau, MAP2, and α-synuclein. Moreover, we examined whether the Aβ granules in the hippocampus correspond to heparan sulphate proteoglycan (HSPG) positive granules previously described in this animal model. The results showed that Aβ granules correspond to the HSPG granular structures, being syndecan-2, a protein involved in the remodeling of dendritic spines, the type of HSPG found. Tau and MAP2, but not α-synuclein depositions, were also found in Aβ aggregates. Granules do not appear to have an astrocytic origin, since although some Aβ clusters are associated with astrocyte processes, most clusters are not. On the other hand, the presence of tau, MAP2, and NeuN in Aβ granules suggests a neuronal origin. As the components identified in Aβ granules are characteristic of the aggregates present in some neurodegenerative diseases, the SAMP8 model seems to be appropriate for the study of the processes involved in these pathologies.


An exploratory study of loading and morphometric factors associated with specific failure modes in fatigue testing of lumbar motion segments.
There is currently little information regarding factors associated with specific modes of motion segment failure using a fatigue failure model. Thirty-six human lumbar motion segments were fatigue tested using spinal compressive and shear loads that simulated lifting a 9 kg weight in three torso flexion angles (0 degrees, 22.5 degrees, and 45 degrees). Twenty-five segments failed via fatigue prior to the 10,000 cycle maximum. These specimens were visually inspected and dissected so that the mode(s) of failure could be determined. Failure modes included endplate fractures (classified into nine varieties), vertebral body fractures, and/or zygapophysial joint disruption. Logistic regression analyses were performed to determine whether certain morphometric variables, amount of motion segment flexion, disk degeneration scores, and/or loading characteristics were associated with the occurrence of specific failure modes. Results indicated that stellate endplate fractures were associated with increased posterior shear forces (P < 0.05) and less degenerated discs (P < 0.01). Fractures running laterally across the endplate were associated with motion segments having larger volumes (P < 0.01). Endplate depression was more common in smaller specimens (P < 0.01), as well as those experiencing increased posterior shear force (P < 0.05). Zygapophysial joint damage was more likely to occur in a neutral posture (P < 0.01). These results suggest that prediction of failure modes (e.g., specific endplate fracture patterns) may be possible (at least for older specimens) given knowledge of the spinal loads along with certain characteristics of the lumbar spine.


Attacks against health care in Syria, 2015-16: results from a real-time reporting tool.
Collecting credible data on violence against health services, health workers, and patients in war zones is a massive challenge, but crucial to understanding the extent to which international humanitarian law is being breached. We describe a new system used mainly in areas of Syria with a substantial presence of armed opposition groups since November, 2015, to detect and verify attacks on health-care services and describe their effect. All Turkey health cluster organisations with a physical presence in Syria, either through deployed and locally employed staff, were asked to participate in the Monitoring Violence against Health Care (MVH) alert network. The Turkey hub of the health cluster, a UN-activated humanitarian health coordination body, received alerts from health cluster partners via WhatsApp and an anonymised online data-entry tool. Field staff were asked to seek further information by interviewing victims and other witnesses when possible. The MVH data team triangulated alerts to identify individual events and distributed a preliminary flash update of key information (location, type of service, modality of attack, deaths, and casualties) to partners, WHO, United Nations Office for the Coordination of Humanitarian Affairs, and donors. The team also received and entered alerts from several large non-health cluster organisations (known as external partners, who do their own information-gathering and verification processes before sharing their information). Each incident was then assessed in a stringent process of information-matching. Attacks were deemed to be verified if they were reported by a minimum of one health cluster partner and one external partner, and the majority of the key datapoints matched. Alerts that did not meet this standard were deemed to be unverified. Results were tabulated to describe attack occurrence and impact, disaggregated where possible by age, sex, and location. Between early November, 2015, and Dec 31 2016, 938 people were directly harmed in 402 incidents of violence against health care: 677 (72%) were wounded and 261 (28%) were killed. Most of the dead were adult males (68%), but the highest case fatality (39%) was seen in children aged younger than 5 years. 24% of attack victims were health workers. Around 44% of hospitals and 5% of all primary care clinics in mainly areas with a substantial presence of armed opposition groups experienced attacks. Aerial bombardment was the main form of attack. A third of health-care services were hit more than once. Services providing trauma care were attacked more than other services. The data system used in this study addressed double-counting, reduced the effect of potentially biased self-reports, and produced credible data from anonymous information. The MVH tool could be feasibly deployed in many conflict areas. Reliable data are essential to show how far warring parties have strayed from international law protecting health care in conflict and to effectively harness legal mechanisms to discourage future perpetrators. None.


ADAM metallopeptidase domain 17 (ADAM17) is naturally processed through major histocompatibility complex (MHC) class I molecules and is a potential immunotherapeutic target in breast, ovarian and prostate cancers.
Selection of suitable antigens is critical for the development of cancer vaccines. Most desirable are over-expressed cell surface proteins that may serve as targets for both antibodies and T cells, thus maximizing a concerted immune response. Towards this goal, we characterized the relevance of tumour necrosis factor-α-converting enzyme (ADAM17) for such targeted therapeutics. ADAM17 is one of the several metalloproteinases that play a key role in epidermal growth factor receptor (EGFR) signalling and has recently emerged as a new therapeutic target in several tumour types. In the present study, we analysed the expression profile of ADAM17 in a variety of normal and cancer cells of human origin and found that this protein is over-expressed on the surface of several types of cancer cells compared to the normal counterparts. Furthermore, we analysed the presentation of a human leucocyte antigen (HLA)-A2-restricted epitope from ADAM17 protein to specific T cells established from normal donors as well as ovarian cancer patients. Our analysis revealed that the HLA-A2-restricted epitope is processed efficiently and presented by various cancer cells and not by normal cells. Tumour-specific T cell activation results in the secretion of both interferon-γ and granzyme B that can be blocked by HLA-A2 specific antibodies. Collectively, our data present evidence that ADAM17 can be a potential target antigen to devise novel immunotherapeutic strategies against ovarian, breast and prostate cancer.


Arthroscopic lavage treatment in rheumatoid arthritis of the knee.
To assess the efficacy of outpatient arthroscopic lavage in rheumatoid arthritis (RA) of the knee. 9 patients with RA and active synovitis of at least one knee were selected. All patients were taking disease modifying antirheumatic drugs and nonsteroidal antiinflammatory drugs and had failed intraarticular corticosteroid injection of the knee. Using the 1.9 mm office arthroscope and strict sterile technique the affected knee was lavaged with at least 750 cc of normal saline. At the end of the procedure 40 mg triamcinolone acetonide was injected through the arthroscope. Assessment was done at baseline and 4, 8, and 12 weeks after the lavage using a visual analog scale for pain and 50 foot walk time. 8 of the 9 patients showed marked improvement in their pain and walk time. This effect was maintained at least 12 weeks after the procedure. Office arthroscopic lavage treatment is beneficial in a selected group of patients. This procedure is simple and well tolerated without major complications, and may be an option when more conservative therapies have failed.


Physical Symptoms, Unmet Needs, and Quality of Life in Thai Cancer Survivors after the Completion of Primary Treatment.
This study investigated physical symptoms, unmet supportive care needs, and quality of life (QoL) perception among different types of Thai cancer survivors who had completed first-line treatment. A cross-sectional study recruited breast, gynecological, colorectal, lung, and head and neck cancer survivors (n = 236) who were attending follow-up visits at a regional cancer hospital in central Thailand. Data were collected by the Physical Symptom Concerns Survey, the Cancer Survivors' Unmet Needs Scale, and a single item measuring global QoL. Descriptive statistics, one-way analysis of variance (ANOVA), and Welch's ANOVA were used for data analysis. Cancer survivors generally perceived good QoL, with significantly low QoL for lung cancer survivors (P < 0.001). There were no differences in symptom experiences among the five cancer groups, except for pain, which was significantly higher in lung cancer survivors than in the other four groups. The most frequently reported symptoms across all groups were numbness in the hands/feet, sleep disturbances, fatigue, and pain. The top unmet supportive care need among all participants was related to concerns of cancer recurrence (44.5%). Head and neck cancer survivors reported the highest number of unmet needs among the five cancer groups. This study mapped the unmet supportive care needs in Thai cancer patients and showed that patients with head and neck cancer and lung cancer were strongly affected. A survivorship care plan focusing on managing physical symptoms and providing supportive and psychosocial care should be developed to meet the needs of each cancer survivor group and to enhance QoL after the completion of treatment.


Measurement characteristics of activity-related psychosocial measures in 8- to 10-year-old African-American girls in the Girls Health Enrichment Multisite Study (GEMS).
This paper presents reliability and validity analyses of physical activity-related psychosocial questionnaires completed by 8- to 10-year-old African-American girls at baseline and follow-up assessments of pilot intervention studies in the Girls health Enrichment Multi-site Study (GEMS). Two hundred ten girls participated in the GEMS 12-week pilot studies and had their height and weight measured, wore an accelerometer for 3 days and completed a measure of their usual physical activity (PA) at baseline and after the 12-week intervention. Subgroups of girls also completed physical activity-related psychosocial measures at these two time points including: (a) self-concept; (b) self-efficacy; (c) outcome expectancies; and d) preferences. Principal components analysis was conducted on the psychosocial measures obtained at baseline. Cronbach's alpha and test-retest reliability were computed. Convergent validity was assessed by correlating the baseline psychosocial measures with baseline physical activity measures and body mass index (BMI). The following sub-scales were derived: Activity Preference, Positive Expectancies and Negative Expectancies for physical activity. Physical Performance Self-Concept and Self-Efficacy for physical activity were kept as single dimensional scales. Sub-scales, derived from principal components analyses, were Activity Preference, Positive Expectancies, and Negative Expectancies for physical activity. Internal consistency estimates for the various scales were substantial to excellent (0.67-0.85), while test-retest reliability estimates were fair to moderate (0.22-0.56). Correlations between the PA psychosocial sub-scales and measured levels of activity measures showed evidence of convergent validity for the Activity Preference sub-scale, although social desirability may have influenced the significant associations observed. The Activity Preference was a fairly reliable and valid measure. Further studies are needed to examine the utility of activity-related psychosocial measures in interventions to increase physical activity among preadolescent African-American girls.


Premotor cortex: sensory cues and movement.
There are suggestions that premotor cortex might play a role either in the execution of axial and proximal movements or in the sensory guidance of movement. Monkeys with bilateral premotor lesions were therefore studied on a series of behavioural tests; the tasks differed either in the movements to be performed or in the nature of the sensory cues that guided the animals. It was found that the success or failure of the monkeys depended on the way in which they received instructions as to what to do. These results are consistent with the view that premotor cortex is involved in the direction of movement but not in its execution.


Predicting transepithelial phototherapeutic keratectomy outcomes using Fourier domain optical coherence tomography.
The aim of this study was to use Fourier domain optical coherence tomography to predict transepithelial phototherapeutic keratectomy outcomes. This is a prospective case series. Subjects with anterior stromal corneal opacities underwent an excimer laser phototherapeutic keratectomy (PTK) combined with a photorefractive keratectomy using the VISX S4 excimer laser (AMO, Inc, Santa Ana, CA). Preoperative and postoperative Fourier domain optical coherence tomography images were used to develop a simulation algorithm to predict treatment outcomes. Main outcome measures included preoperative and postoperative uncorrected distance visual acuities and corrected distance visual acuity. Nine eyes of 8 patients were treated. The nominal ablation depth was 75 to 177 μm centrally and 62 to 185 μm peripherally. Measured PTK ablation depths were 20% higher centrally and 26% higher peripherally, compared with those for laser settings. Postoperatively, the mean uncorrected distance visual acuity was 20/41 (range, 20/25-20/80) compared with 20/103 (range, 20/60-20/400) preoperatively. The mean corrected distance visual acuity was 20/29 (range, 20/15-20/60) compared with 20/45 (range, 20/30-20/80) preoperatively. The MRSE was +1.38 ± 2.37 diopters (D) compared with -2.59 ± 2.83 D (mean ± SD). The mean astigmatism magnitude was 1.14 ± 0.83 D compared with 1.40 ± 1.18 D preoperatively. Postoperative MRSE correlated strongly with ablation settings, central and peripheral epithelial thickness (r = 0.99, P < 0.00001). Central islands remained difficult to predict and limited visual outcomes in some cases. Optical coherence tomography measurements of opacity depth and 3-dimensional ablation simulation provide valuable guidance in PTK planning. Post-PTK refraction may be predicted with a regression formula that uses epithelial thickness measurements obtained by optical coherence tomography. The laser ablation rates described in this study apply only to the VISX laser.


Lung recruitment in acute respiratory distress syndrome: what is the best strategy?
Supporting patients with acute respiratory distress syndrome (ARDS) using a low tidal volume strategy is a standard practice in the ICU. Recruitment maneuvers can be used to augment other methods, like positive end-expiratory pressure and positioning, to improve aerated lung volume. Clinical practice varies widely, and optimal method and patient selection for recruitment maneuvers have not been determined. Recent developments include experimental and clinical evidence that a stepwise extended recruitment maneuver may match the improvement in aerated lung volume seen with sustained inflation traditionally used, with less adverse effects. Positioning and other chest wall modifications may be useful adjuncts to recruitment maneuvers. In addition, evidence from clinical studies in the operating room suggests that recruitment maneuvers, as a component of an open lung strategy, may be helpful for mechanically ventilated patients with normal lungs. As a component of ventilation strategy for patients with ARDS, the use of recruitment maneuvers, especially a stepwise maneuver, in addition to adequate positive end-expiratory pressure and appropriate positioning, is suggested by currently available data. Until their effect on clinical outcomes is further defined, the use of recruitment maneuvers in ARDS and other settings will continue to be guided by individual clinician experience and patient factors.


Appeals that matter or not on a moratorium on the deployment of the fifth generation, 5G, for microwave radiation.
Radiofrequency (RF) radiation in the frequency range of 30 kHz-300 GHz is classified as a 'possible' human carcinogen, Group 2B, by the International Agency for Research on Cancer (IARC) since 2011. The evidence has since then been strengthened by further research; thus, RF radiation may now be classified as a human carcinogen, Group 1. In spite of this, microwave radiations are expanding with increasing personal and ambient exposure. One contributing factor is that the majority of countries rely on guidelines formulated by the International Commission on Non-Ionizing Radiation Protection (ICNIRP), a private German non-governmental organization. ICNIRP relies on the evaluation only of thermal (heating) effects from RF radiation, thereby excluding a large body of published science demonstrating the detrimental effects caused by non-thermal radiation. The fifth generation, 5G, for microwave radiation is about to be implemented worldwide in spite of no comprehensive investigations of the potential risks to human health and the environment. In an appeal sent to the EU in September, 2017 currently >260 scientists and medical doctors requested for a moratorium on the deployment of 5G until the health risks associated with this new technology have been fully investigated by industry-independent scientists. The appeal and four rebuttals to the EU over a period of >2 years, have not achieved any positive response from the EU to date. Unfortunately, decision makers seem to be uninformed or even misinformed about the risks. EU officials rely on the opinions of individuals within the ICNIRP and the Scientific Committee on Emerging and Newly Identified Health Risks (SCENIHR), most of whom have ties to the industry. They seem to dominate evaluating bodies and refute risks. It is important that these circumstances are described. In this article, the warnings on the health risks associated with RF presented in the 5G appeal and the letters to the EU Health Commissioner since September, 2017 and the authors' rebuttals are summarized. The responses from the EU seem to have thus far prioritized industry profits to the detriment of human health and the environment.


Development of a striving to avoid inferiority scale.
Social rank theory suggests that mood variation is linked to the security a person feels in his/her social domain and the extent to which they are sensitive to involuntary subordination (e.g. feeling defeated and feeling inferior). Previous studies looking at rank-related and competitive behaviour have often focused on striving for dominance, whereas social rank theory has focused on striving to avoid inferiority. This study set out to develop a measure of 'Striving to Avoid Inferiority' (SAIS) and assess its relationship to other rank and mood-related variables. We hypothesized two factors: one we called insecure striving, relating to fear of rejection/criticism for 'not keeping up', and the second we called secure non-striving, relating to feeling socially acceptable and valued regardless of whether one succeeds or not. This scale was given to 207 undergraduates. The SAIS had good psychometric properties, with the two factors of insecure striving and secure non-striving strongly supported by exploratory factor analysis. Both factors were significantly (though contrastingly) related to various fears of rejection, need for validation, hypercompetitive attitudes, feeling inferior to others, submissive behaviour and indicators of stress, anxiety and depression. Striving to avoid inferiority was a significant predictor of psychopathologies, especially where individuals perceived themselves to have low social rank.


An Approach to Improve the Performance of PM Forecasters.
The particulate matter (PM) concentration has been one of the most relevant environmental concerns in recent decades due to its prejudicial effects on living beings and the earth's atmosphere. High PM concentration affects the human health in several ways leading to short and long term diseases. Thus, forecasting systems have been developed to support decisions of the organizations and governments to alert the population. Forecasting systems based on Artificial Neural Networks (ANNs) have been highlighted in the literature due to their performances. In general, three ANN-based approaches have been found for this task: ANN trained via learning algorithms, hybrid systems that combine search algorithms with ANNs, and hybrid systems that combine ANN with other forecasters. Independent of the approach, it is common to suppose that the residuals (error series), obtained from the difference between actual series and forecasting, have a white noise behavior. However, it is possible that this assumption is infringed due to: misspecification of the forecasting model, complexity of the time series or temporal patterns of the phenomenon not captured by the forecaster. This paper proposes an approach to improve the performance of PM forecasters from residuals modeling. The approach analyzes the remaining residuals recursively in search of temporal patterns. At each iteration, if there are temporal patterns in the residuals, the approach generates the forecasting of the residuals in order to improve the forecasting of the PM time series. The proposed approach can be used with either only one forecaster or by combining two or more forecasting models. In this study, the approach is used to improve the performance of a hybrid system (HS) composed by genetic algorithm (GA) and ANN from residuals modeling performed by two methods, namely, ANN and own hybrid system. Experiments were performed for PM2.5 and PM10 concentration series in Kallio and Vallila stations in Helsinki and evaluated from six metrics. Experimental results show that the proposed approach improves the accuracy of the forecasting method in terms of fitness function for all cases, when compared with the method without correction. The correction via HS obtained a superior performance, reaching the best results in terms of fitness function and in five out of six metrics. These results also were found when a sensitivity analysis was performed varying the proportions of the sets of training, validation and test. The proposed approach reached consistent results when compared with the forecasting method without correction, showing that it can be an interesting tool for correction of PM forecasters.


Comparison of three supraglottic devices in anesthetised paralyzed children undergoing elective surgery.
The newest variation of the i-gel supraglottic airway is a pediatric version. This study was designed to investigate the usefulness of the size 2 i-gel compared with the ProSeal laryngeal mask airway (PLMA) and classic laryngeal mask airway (cLMA) of the same size in anesthetized, paralyzed children. A prospective, randomized, single-blinded study was conducted in a tertiary care teaching hospital. Ninety ASA grade I-II patients undergoing lower abdominal, inguinal and orthopedic surgery were included in this prospective study. The patients were randomly assigned to the i-gel, PLMA and cLMA groups (30 patients in each group). Size 2 supraglottic airway was inserted according to the assigned group. We assessed ease of insertion, hemodynamic data, oropharyngeal sealing pressure and postoperative complications. There were no differences in the demographic and hemodynamic data among the three groups. The airway leak pressure of the i-gel group (27.1±2.6 cmH(2)O) was significantly higher than that of the PLMA group (22.73±1.2 cmH(2)O) and the cLMA group (23.63±2.3 cmH(2)O). The success rates for first attempt of insertion were similar among the three devices. There were no differences in the incidence of postoperative airway trauma, sore throat or hoarse cry in the three groups. Hemodynamic parameters, ease of insertion and postoperative complications were comparable among the i-gel, PLMA and cLMA groups, but airway sealing pressure was significantly higher in the i-gel group.


Adding evidence of the effects of treatments into relevant Wikipedia pages: a randomised trial.
To investigate the effects of adding high-grade quantitative evidence of outcomes of treatments into relevant Wikipedia pages on further information-seeking behaviour by the use of routinely collected data. Wikipedia, Cochrane summary pages and the Cochrane Library. Randomised trial. Wikipedia pages which were highly relevant to up-to-date Cochrane Schizophrenia systematic reviews that contained a Summary of Findings table. Eligible Wikipedia pages in the intervention group were seeded with tables of best evidence of the effects of care and hyperlinks to the source Cochrane review. Eligible Wikipedia pages in the control group were left unchanged. Routinely collected data on access to the full text and summary web page (after 12 months). We randomised 70 Wikipedia pages (100% follow-up). Six of the 35 Wikipedia pages in the intervention group had the tabular format deleted during the study but all pages continued to report the same data within the text. There was no evidence of effect on either of the coprimary outcomes: full-text access adjusted ratio of geometric means 1.30, 95% CI: 0.71 to 2.38; page views 1.14, 95% CI: 0.6 to 2.13. Results were similar for all other outcomes, with exception of Altmetric score for which there was some evidence of clear effect (1.36, 95% CI: 1.05 to 1.78). The pursuit of fair balance within Wikipedia healthcare pages is impressive and its reach unsurpassed. For every person who sought and clicked the reference on the 'intervention' Wikipedia page to seek more information (the primary outcome), many more are likely to have been informed by the page alone. Enriching Wikipedia content is, potentially, a powerful way to improve health literacy and it is possible to test the effects of seeding pages with evidence. This trial should be replicated, expanded and developed. IRCT2017070330407N2.


Child sexual abuse: is it a risk factor for pregnancy?
This paper is a report of a study of the relationship of post-traumatic stress symptoms, depression, and health status to high risk pregnancy status in survivors of childhood sexual abuse. Studies examining the long-term effects of childhood sexual abuse have delineated diverse psychological, cognitive, and social difficulties in adult survivors that often manifest somatically. A random sample of 1835 mid-pregnant Jewish women was recruited in Israel over an 18-month period in 2005-2007. Participants were divided into three sub-groups consisting of the different combinations between pregnancy at risk (yes/no), childhood sexual abuse (yes/no), other than childhood sexual abuse trauma (yes no), and no trauma (yes/no). They completed a self-administered questionnaire consisting of five scales: a demographic variables scale, the Post-traumatic Stress Disorder Symptom Scale, Center for Epidemiologic Studies Depression Scale, Traumatic Events Questionnaire, and Childhood Sexual Experiences Scale. Pregnant survivors of childhood sexual abuse suffered higher distress levels which heightened poor health, hence increasing the probability of high risk pregnancy compared to women who had had other than sexual abuse trauma or reported no trauma. Post traumatic stress symptoms and avoidance (a sub-category) were found to explain chronic illnesses, whereas depression was found to explain gynecological problems in pregnant sexually-abused survivors. Healthcare workers need to recognize and address the psychological state of pregnant child sexual abuse survivors. Screening of pregnant women for child sexual abuse is needed to assess survivors' psychological well-being and recognize their unique concerns during pregnancy monitoring.


Population-based, multi-generational family clustering study of social anxiety disorder and avoidant personality disorder.
We aimed to provide unbiased estimates of familial risk and heritability of social anxiety disorder (SAD) and avoidant personality disorder (AVPD). We identified 18 399 individuals diagnosed with SAD and 2673 with AVPD in the Swedish National Patient Register between 1997 and 2009. Risks (odds ratios; OR) for SAD in all biological and non-biological relatives of probands, compared to relatives of unaffected individuals were calculated. We also estimated the risks for AVPD in relatives of probands with SAD. The risk for SAD among relatives of SAD probands increased proportionally to the degree of genetic relatedness. The risks for first-degree relatives [OR 4.74, 95% confidence interval (CI) 4.28-5.25] were significantly higher than for second-degree and third-degree relatives. Second-degree relatives (OR 2.30, 95% CI 2.01-2.63) had significantly higher risk than third-degree relatives (OR 1.72, 95% CI 1.52-1.94). Relatives at similar genetic distances had similar risks for SAD, despite different degrees of shared environment. Heritability was estimated to be approximately 56%. There were no significant sex differences in the familial patterns. The risk of AVPD in relatives of SAD probands was significantly elevated, even after excluding individuals with both diagnoses (first-degree OR 3.54, second-degree OR 2.20, third-degree OR 1.62). Non-biological relatives (spouses/partners) also had elevated risks for both SAD (OR 4.01) and AVPD (OR 3.85). SAD clusters in families primarily due to genetic factors. SAD and AVPD are aetiologically related and may represent different expressions of the same vulnerability. The strong marital concordance observed in SAD/AVPD may indicate assortative mating but the exact mechanisms and implications require further investigation.


Can interaction of materials with the dentin-pulp complex contribute to dentin regeneration?
Understanding outcomes of the interaction between a dental material and tooth tissue is important in terms not only of biocompatibility but also of the potential for the material to modulate the response of the tissue. This interaction is influenced by many factors, including the chemistry of the material and any of its eluted components or degradation products, and the manner in which the tissue responds to these agents. Past studies of this interaction have primarily been aimed at identifying cytotoxic effects. More recently, investigations have focused on specific cellular responses, and in particular, on understanding how the materials themselves actually may contribute to regenerative processes in the tooth. Recent work has demonstrated the solubilization of proteins from dentin exposed to certain materials, such as calcium hydroxide, mineral trioxide aggregate, and acidic solutions that relate to those used in dentin bonding agents, with the subsequent modulation by these proteins of gene expression in odontoblast-like cells. This work suggests that dentin bridge formation under such materials may be stimulated through this process. Thus, there is much merit in examining both how new dental materials can be developed and how more traditional ones can be modified to preferentially stimulate regenerative processes when preferred. This review summarizes current knowledge about the potential beneficial effects derived from the interaction of dental materials with the dentin-pulp complex, as well as potential future developments in this exciting field.


Validation of a Doppler echocardiographic method for calculating severity of discrete stenotic obstructions in a canine preparation with a pulmonary arterial band.
The purpose of this study was to develop an open-chest animal preparation to validate the accuracy of a two-dimensional Doppler echocardiographic method for estimating pressure drops across discrete stenotic obstructions. Six mongrel dogs underwent median sternotomy and catheters were placed in the right ventricle, distal main pulmonary artery, and aorta of each. A 1/8 inch umbilical tape was sewn to the posterior rim of the pulmonary artery just above the anulus and was progressively tightened to vary the degree of stenosis. Ultrasound and Doppler studies were performed with a 2.5 MHz phased-array unit with capabilities for pulsed or continuous-mode Doppler and real-time imaging. Peak systolic main pulmonary arterial flow velocities were recorded by Doppler echocardiography within the jet distal to the band from an oblique parasternal short-axis echocardiographic view and corrected for angle of incidence between the direction of Doppler sampling and the presumed direction of flow. Doppler velocities were converted to gradients with a simplification of the Bernoulli equation (gradient = 4 X maximal Doppler flow velocity2 ). Maximal Doppler-determined systolic pulmonary arterial velocities showed a good linear correlation with the 63 measured pressure drops (r = .95, SEE +/- 36.3 cm/sec). An excellent correlation was also found between Doppler-calculated and actual pressure gradients (r = .96, SEE +/- 7.26 mm Hg). Our results suggest that this Doppler method for measuring gradients across discrete stenotic obstructions may be quite accurate in clinical applications.


Cost-effectiveness of glaucoma interventions in Barbados and Ghana.
More than 90% of blindness worldwide exists in the developing world, but information on the social and economic burden and the cost-effectiveness of treatment in these settings is often limited or nonexistent. We demonstrate the use of computer modeling to simulate the current and future epidemiology, outcomes, and treatment of primary open-angle glaucoma in high-incidence populations of the developing world. A previously validated vision model was modified to simulate the incidence progression and social and economic outcomes of glaucoma in Barbados, which was the source of epidemiology data, and Ghana, which has similar propensity for glaucoma but lower socioeconomic development. We then assessed the cost-effectiveness of hypothetical case-finding and treatment scenarios, including U.S. guideline-level care and one-time laser surgery. Barbados incurs relatively greater social and economic burden from glaucoma than Ghana. In Barbados, population screening followed by U.S. guideline levels of care appears to be highly cost-effective. Because of a younger population with higher mortality at younger ages, glaucoma appears to cause less visual impairment and blindness in Ghana than in Barbados, resulting in lower per capita disability and productivity losses. Population screening or guideline-level treatment scenarios were generally not cost-effective in Ghana, but treating self-referring patients with a hypothetical one-time laser surgery was highly cost-effective relative to World Health Organization willingness to pay thresholds. The social and economic burden of glaucoma is higher in developed nations because of increased life expectancy, an older population age profile, and higher per capita gross domestic product. Similarly, lower mortality rates and higher per capita gross domestic product increase the relative cost-effectiveness of screening and treatment interventions intended to mitigate glaucoma burden.


Numerically bridging lamellipodial and filopodial activity during cell spreading reveals a potentially novel trigger of focal adhesion maturation.
We present a novel approach to modeling cell spreading, and use it to reveal a potentially central mechanism regulating focal adhesion maturation in various cell phenotypes. Actin bundles that span neighboring focal complexes at the lamellipodium-lamellum interface were assumed to be loaded by intracellular forces in proportion to bundle length. We hypothesized that the length of an actin bundle (with the corresponding accumulated force at its adhesions) may thus regulate adhesion maturation to ensure cell mechanical stability and morphological integrity. We developed a model to test this hypothesis, implementing a "top-down" approach to simplify certain cellular processes while explicitly incorporating complexity of other key subcellular mechanisms. Filopodial and lamellipodial activities were treated as modular processes with functional spatiotemporal interactions coordinated by rules regarding focal adhesion turnover and actin bundle dynamics. This theoretical framework was able to robustly predict temporal evolution of cell area and cytoskeletal organization as reported from a wide range of cell spreading experiments using micropatterned substrates. We conclude that a geometric/temporal modeling framework can capture the key functional aspects of the rapid spreading phase and resultant cytoskeletal complexity. Hence the model is used to reveal mechanistic insight into basic cell behavior essential for spreading. It demonstrates that actin bundles spanning nascent focal adhesions such that they are aligned to the leading edge may accumulate centripetal endogenous forces along their length, and could thus trigger focal adhesion maturation in a force-length dependent fashion. We suggest that this mechanism could be a central "integrating" factor that effectively coordinates force-mediated adhesion maturation at the lamellipodium-lamellum interface.


Z-360, a novel therapeutic agent for pancreatic cancer, prevents up-regulation of ephrin B1 gene expression and phosphorylation of NR2B via suppression of interleukin-1 β production in a cancer-induced pain model in mice.
Z-360 is an orally active cholecystokinin-2 (CCK2)/gastrin receptor antagonist currently under development as a therapeutic drug for pancreatic cancer. It was previously reported that Z-360 treatment in combination with gemcitabine prolonged the survival period in a lethal pancreatic cancer xenograft model in mice. In a phase Ib/IIa clinical study, Z-360 treatment displayed a trend of reduced pain in patients with advanced pancreatic cancer in combination with gemcitabine including analgesics such as opioids. Here, we investigated the mechanism of analgesic action of Z-360 in a severe cancer-induced pain model in mice, which is considered to be opioid-resistant, by examining ephrin B1 gene expression, N-methyl-D-aspartate receptor NR2B subunit phosphorylation, and interleukin-1β (IL-1β) production. In a mouse model of cancer-induced pain, ephrin B1 gene expression in dorsal root ganglia (DRGs) and the phosphorylation of NR2B in the spinal cord were induced. Z-360 treatment inhibited both ephrin B1 gene expression and the phosphorylation of NR2B. In addition, IL-1β production increased in the cancer-inoculated hind paw of mice, but could be suppressed by treatment with Z-360. Moreover, we observed that the CCK1 receptor antagonist devazepide similarly suppressed up-regulation of ephrin B1 gene expression and IL-1β production, and that the intraperitoneal injection of sulfated CCK-8 induced the production of IL-1β in the cancer-inoculated region. We have identified a novel pain cascade, in which IL-1β production in cancer-inoculated regions induces ephrin B1 gene expression in DRGs and then ephrin B1 enhances the tyrosine phosphorylation of NR2B via Eph B receptor in the spinal cord. Notably, Z-360 relieves cancer-induced pain by preventing this pain cascade through the suppression of IL-1β production, likely via the blockade of CCK1 receptor. The pre-clinical results presented here support the analgesic action of Z-360 in pancreatic cancer patients with severe, opioid-resistant pain. Pre-clinical and clinical results have demonstrated that Z-360 combined with gemcitabine represents a promising pancreatic cancer therapy approach with characteristic analgesic effects in addition to the prolongation of survival.


The effect of antioxidant properties of aqueous garlic extract and Nigella sativa as anti-schistosomiasis agents in mice.
The aim of this study was to assess the antioxidant and anti-schistosomal activities of the garlic extract (AGE) and Nigella sativa oil (NSO) on normal and Schistosoma mansoni-infected mice. AGE (125 mg kg-1, i.p.) and NSO (0.2 mg kg-1, i.p.) were administrated separately or in combination for successive 28 days, starting from the 1st day post infection (pi). All mice were sacrificed at weeks 7 pi. Hematological and biochemical parameters including liver and kidney functions were measured to assess the progress of anemia, and the possibility of the tissue damage. Serum total protein level, albumin, globulin and cholesterol were also determined. Malondialdehyde (MDA) and glutathione (GSH) levels were determined in the liver tissues as biomarkers for oxidative and reducing status, respectively. The possible effect of the treatment regimens on Schistosoma worms was evaluated by recording percentage of the recovered worms, tissue egg and oogram pattern. Result showed that, protection with AGE and NSO prevented most of the hematological and biochemical changes and markedly improved the antioxidant capacity of schistosomiasis mice compared to the infected-untreated ones. In addition, remarkable reduction in worms, tissue eggs and alteration in oogram pattern were recorded in all the treated groups. The antioxidant and antischistosomal action of AGE and NSO was greatly diverse according to treatment regimens. These data point to these compounds as promising agents to complement schistosomiasis specific treatment.


Claw length recommendations for dairy cow foot trimming.
The aim was to describe variation in length of the dorsal hoof wall in contact with the dermis for cows on a single farm, and hence, derive minimum appropriate claw lengths for routine foot trimming. The hind feet of 68 Holstein-Friesian dairy cows were collected post mortem, and the internal structures were visualised using x-ray µCT. The internal distance from the proximal limit of the wall horn to the distal tip of the dermis was measured from cross-sectional sagittal images. A constant was added to allow for a minimum sole thickness of 5 mm and an average wall thickness of 8 mm. Data were evaluated using descriptive statistics and two-level linear regression models with claw nested within cow. Based on 219 claws, the recommended dorsal wall length from the proximal limit of hoof horn was up to 90 mm for 96 per cent of claws, and the median value was 83 mm. Dorsal wall length increased by 1 mm per year of age, yet 85 per cent of the null model variance remained unexplained. Overtrimming can have severe consequences; the authors propose that the minimum recommended claw length stated in training materials for all Holstein-Friesian cows should be increased to 90 mm.


Kinetic identification of an intracellular calcium compartment sensitive to phosphate and dinitrophenol in intact isolated rabbit aorta.
Previous work from this laboratory revealed the presence of at least three distinct intracellular calcium compartments in intact segments of rabbit aorta. In this study one of these intracellular compartments is shown to be sensitive to dinitrophenol and to increased extracellular phosphate. Intact aortic segments were loaded with 45Ca in bicarbonate-buffered physiologic salt solution for 1 hour, and then transferred to a flow-through chamber perfused with physiologic salt solution. Effluent from the chamber was collected for 8 hours, and 45Ca efflux curves were analyzed using compartmental analysis. When aortic segments were loaded and washed out in dinitrophenol, the slowest component of the efflux curve was less prominent; in high phosphate it was more prominent. The rate constant changes required to account for these data were primarily in the exchange between the cytosolic and slowest intracellular calcium compartment, suggesting that the slowest calcium compartment resolved during the 8-hour washout was mitochondrial. This compartment contained 5.4 +/- 3.2 nmol calcium/g wet wt. tissue. The calcium flux across its membranes was 0.32 +/- 0.04 nmol min-1g-1. Because this flux is much smaller than the plasma-membrane calcium flux, we suggest that, in normal physiological circumstances, plasma-membrane extrusion is more important for the removal of Ca from the smooth muscle cytosol than is uptake into this slow intracellular compartment.


Minimizing mistakes in clinical diagnosis.
It would be quite reasonable for us to expect the progress made in diagnostic technology to be accompanied by a parallel improvement in diagnostic accuracy. In reality, however, the frequency of misdiagnoses remains the same, despite the fast progress which has been made by medical technology in the last 30 years. Autopsy is the best source of information on diagnostic accuracy. According to one hypothesis, an increase in the number of autopsies performed and the follow-up on them could reduce the number of diagnostic mistakes. In recent times, however, the number of autopsies in comparison with the registered number of deaths has been declining steeply. We studied the autopsy reports for 1997, kept at the archive of the Institute for Forensic Medicine. We only took into account the deaths which occurred within 24 h of admittance to the emergency wards of the Ljubljana University Hospital, including those patients who died subsequently as a consequence of accident or injury. We also included cases of sudden deaths which occurred during operating or within 24 h after it. Following selection, we analyzed 444 out of the total of 921 autopsy reports, for each of which we carried out a comparison between the postmortem diagnosis and the clinical diagnosis, contained in the medical report on the death and the causes of death, which is modeled on WHO recommendations, i.e., the International Classification of Diseases (ICD), and in the medical documents, if any were submitted. Data are entered in these by using the ABC system where: A) direct cause of death, B) are circumstances that influenced the occurrence of death, and C) is original cause of death. The findings were then organized into five groups, depending on the degree to which the clinical diagnosis agreed with the postmortem diagnosis. The first group is comprised of the cases where the clinical and postmortem diagnoses agree completely; the second group is comprised of the cases of partial disagreement on the direct cause of death; the third group is comprised of the cases of disagreement on the original disease; the fourth group, of complete disagreement between the clinical and postmortem diagnoses. The fifth group is comprised of those cases where, under the ABC standards on the classification of diseases, injuries and causes of deaths as specified by the WHO, the documentation was incomplete. A complete agreement between the diagnoses was established in 48.87% of cases; partial disagreement in 22.74%; and total disagreement in 13.5%. 9.68% of cases were classified as falling into group 5. For the three diseases that are among the most common causes of death, we established the percentage of agreement, the percentage of overdiagnosis and the percentage of underdiagnosis. The most frequently underdiagnosed disease (in 61% of cases) was pulmonary thromboembolia; in 15% a thromboembolia was confirmed in autopsy. In 24%, a myocardial infarction was not diagnosed clinically and in 60% the clinical diagnosis of a myocardial infarction was confirmed in autopsy. In 33% a heart failure was not diagnosed during the clinical stages but only in autopsy, in 66% the clinical diagnosis of a heart failure was confirmed in autopsy.


Correlates of recovery from alcohol dependence: a prospective study over a 3-year follow-up interval.
Correlates of recovery from alcohol dependence have been identified through a variety of study designs characterized by different strengths and limitations. The goal of this study was to compare correlates of recovery based on a 3-year prospective design with those based on cross-sectional analyses of data from the same source. Data from the 2001 to 2002 Wave 1 and 2004 to 2005 Wave 2 National Epidemiologic Survey on Alcohol and Related Conditions (NESARC) were used to examine baseline characteristics associated with Wave 2 recovery from alcohol dependence, among those who classified with past-year DSM-IV alcohol dependence at Wave 1 (n = 1,172). Abstinent recovery was significantly associated with Black/Asian/Hispanic race/ethnicity, children <1 year of age in the household at baseline, attending religious services greater than or equal to weekly at follow-up, and having initiated help-seeking that comprised/included 12-step participation within <3 years prior to baseline. Nonabstinent recovery was positively associated with being never married at baseline, having job problems or being unemployed in the year preceding baseline, attending religious services less than weekly at follow-up, baseline smoking and volume of ethanol intake, and having terminated a first marriage within <3 years prior to baseline. Findings, including others of marginal significance (0.05 < p < 0.10), generally supported results from prior pseudo-prospective survival analyses with time-dependent covariates but differed in many ways from cross-sectional analyses of Wave 1 NESARC data. Various aspects of study design must be considered when interpreting correlates of recovery. Cross-sectional analyses of lifetime correlates of recovery are highly subject to misinterpretation, but pseudo-prospective survival analyses with time-dependent covariates may yield results as valid as those from prospective studies.


Laser desorption sample transfer for gas chromatography/mass spectrometry.
Ambient mass spectrometry can detect small molecules directly, but complex mixtures can be a challenge. We have developed a method that incorporates small molecule separation based on laser desorption with capture on a solid-phase microextraction (SPME) fiber for injection into a gas chromatography/mass spectrometry (GC/MS) system. Samples on a metal target were desorbed by a 3 µm mid-infrared laser focused to a 250 µm spot and 1.2 mJ pulse energy. The desorbed material was aspirated into a metal tube suspended 1 mm above the laser spot and captured on a SPME fiber. The collected material was injected into a GC/MS instrument for analysis. We have developed a versatile approach for ambient laser desorption sampling onto SPME for GC/MS analysis. The performance of the laser desorption SPME capture GC/MS system was demonstrated for small molecule standards, a mixture of nitroaromatic explosives, and collected cigarette smoke. The utility of ambient laser desorption sampling onto SPME for GC/MS was demonstrated. The performance of the method was evaluated by preparing calibration standards of caffeine over a range from 200 to 1000 ng. Laser desorption ambient sampling of complex mixtures was accomplished using SPME GC/MS.


Recruitment and retention of pregnant women for a behavioral intervention: lessons from the maternal adiposity, metabolism, and stress (MAMAS) study.
Recruiting participants for research studies can be challenging. Many studies fall short of their target or must prolong recruitment to reach it. We examined recruitment and retention strategies and report lessons learned in a behavioral intervention developmental trial to encourage healthy pregnancy weight gain and stress reduction in low-income overweight pregnant women. In the San Francisco Bay area from February 2010 through March 2011, we used direct and indirect strategies to recruit English-speaking overweight and obese pregnant women who were aged 18 to 45, were in the early stages of pregnancy, and who had an annual household income less than 500% of the federal poverty guidelines. Eligible women who consented participated in focus groups or an 8-week behavioral intervention. We identified successful recruiting strategies and sites and calculated the percentage of women who were enrolled and retained. Of 127 women screened for focus group participation, 69 were eligible and enrolled. A total of 57 women participated in 9 focus groups and 3 women completed individual interviews for a completion rate of 87%. During recruitment for the intervention, we made contact with 204 women; 135 were screened, 33% were eligible, and 69.1% of eligible women enrolled. At 1 month postpartum, 82.6% of eligible women completed an assessment. Recruiting at hospital-based prenatal clinics was the highest-yielding strategy. The narrow window of eligibility for enrolling early stage pregnant women in a group intervention presents obstacles. In-person recruitment was the most successful strategy; establishing close relationships with providers, clinic staff, social service providers, and study participants was essential to successful recruitment and retention.


Basilar invagination in osteogenesis imperfecta and related osteochondrodysplasias: medical and surgical management.
Osteogenesis imperfecta (OI) is a heritable disorder of bone development caused by defective collagen synthesis. Basilar invagination is an uncommon but devastating complication of this disease. The authors present a comprehensive strategy for management of craniovertebral anomalies associated with OI and related osteochondrodysplasias. Twenty-five patients with congenital osteochondrodysplasias (18 OI, four Hajdu-Cheney syndrome, and three spondyloepiphyseal dysplasia) and basilar invagination were evaluated between 1985 and 1995. The male/female ratio in this cohort was 1:1. The mean age at presentation was 11.9 years (range 13 months-20 years). Fourteen patients (56%) presented during adolescence (11-15 years of age). Symptoms and signs included headache (76%), lower cranial nerve dysfunction (68%), hyperreflexia (56%), quadriparesis (48%), ataxia (32%), nystagmus (28%), and scoliosis (20%). Four patients (16%) were asymptomatic. Seven (28%) had undergone previous posterior fossa decompression; one had also undergone ventral decompression. Imaging findings included basilar invagination (100%), ventral brainstem compression (84%), hydrocephalus (32%), hindbrain herniation (28%), and syringomyelia/syringobulbia (16%). Patients with hydrocephalus underwent ventricular shunt placement. Reducible basilar invagination (40%) was treated with posterior fossa decompression and occipitocervical fusion. Those with irreducible ventral compression (60%) underwent transoral-transpalatopharyngeal decompression followed by occipitocervical fusion. All patients improved initially. However, basilar invagination progressed radiographically in 80% (symptomatic in 24%) despite successful fusion. Prolonged external orthotic immobilization with the modified Minerva brace afforded symptomatic improvement and arrested progression of the deformity. The mean follow-up period was 5.9 years (range 1.1-10.5 years). Ventral brainstem compression in OI should be treated with ventral decompression, followed by occipitocervical fusion with contoured loop instrumentation to prevent further squamooccipital infolding. Despite fusion, however, basilar invagination tends to progress. Prolonged immobilization (particularly during adolescence) may stabilize symptoms and halt further invagination. This study represents the largest series to date addressing craniovertebral anomalies in OI and related congenital bone softening disorders.


Development of a telemetry and yield-mapping system of olive harvester.
Sensors, communication systems and geo-reference units are required to achieve an optimized management of agricultural inputs with respect to the economic and environmental aspects of olive groves. In this study, three commercial olive harvesters were tracked during two harvesting seasons in Spain and Chile using remote and autonomous equipment that was developed to determine their time efficiency and effective based on canopy shaking for fruit detachment. These harvesters work in intensive/high-density (HD) and super-high-density (SHD) olive orchards. A GNSS (Global Navigation Satellite System) and GSM (Global System for Mobile Communications) device was installed to track these harvesters. The GNSS receiver did not affect the driver's work schedule. Time elements methodology was adapted to the remote data acquisition system. The effective field capacity and field efficiency were investigated. In addition, the field shape, row length, angle between headland alley and row, and row alley width were measured to determinate the optimum orchard design parameters value. The SHD olive harvester showed significant lower effective field capacity values when alley width was less than 4 m. In addition, a yield monitor was developed and installed on a traditional olive harvester to obtain a yield map from the harvested area. The hedge straddle harvester stood out for its highly effective field capacity; nevertheless, a higher field efficiency was provided by a non-integral lateral canopy shaker. All of the measured orchard parameters have influenced machinery yields, whether effective field capacity or field efficiency. A saving of 40% in effective field capacity was achieved with a reduction from 4 m or higher to 3.5 m in alley width for SHD olive harvester. A yield map was plotted using data that were acquired by a yield monitor, reflecting the yield gradient in spite of the larger differences between tree yields.