How to quantify structural anomalies in fluids?
Some fluids are known to behave anomalously. The so-called structural anomaly which means that the fluid becomes less structures under isothermal compression is among the most frequently discussed ones. Several methods for quantifying the degree of structural order are described in the literature and are used for calculating the region of structural anomaly. It is generally thought that all of the structural order determinations yield qualitatively identical results. However, no explicit comparison was made. This paper presents such a comparison for the first time. The results of some definitions are shown to contradict the intuitive notion of a fluid. On the basis of this comparison, we show that the region of structural anomaly can be most reliably determined from the behavior of the excess entropy.


Emergence of GABAergic-dependent regulation of input-specific plasticity in the adult rat prefrontal cortex during adolescence.
The prefrontal cortex (PFC) receives multiple cortical and subcortical afferents that regulate higher order cognitive functions, many of which emerge late in adolescence. However, it remains unclear how these afferents influence PFC processing, especially in light of the protracted, late adolescent maturation of prefrontal GABAergic function. Here we investigated the role of PFC GABAergic transmission in regulating plasticity elicited from the ventral hippocampus and basolateral amygdala, and how such modulation undergoes functional changes during adolescence in rats. In vivo local field potential recordings, combined with prefrontal microinfusion of the GABA-A receptor antagonist picrotoxin, were employed to study the impact of ventral hippocampal and basolateral amygdala high-frequency stimulation on PFC plasticity. Ventral hippocampal-induced PFC plasticity begins to appear only by postnatal days (P) 45-55 with a transient suppression of the evoked response. A switch from transient to long-lasting depression (LTD) of the PFC response emerges after P55 and throughout adulthood (P65-120). Recordings conducted in the presence of picrotoxin revealed that PFC GABAergic transmission is critical for the expression of LTD. In contrast, basolateral amygdala stimulation resulted in PFC long-term potentiation, a form of plasticity that is already enabled by P30 and is insensitive to picrotoxin. The development of ventral hippocampal-dependent PFC LTD is contingent upon the recruitment of local prefrontal GABAergic transmission during adolescence whereas plasticity elicited from the basolateral amygdala is not. Thus, different mechanisms contribute to the refinement of prefrontal plasticity during adolescence as inputs from these two regions are critical for shaping PFC functions.


The use of functional and quantitative assays to study glycoprotein Ib in platelets stored under various in vitro conditions.
There is much evidence to suggest that platelet membrane glycoprotein Ib is involved in the haemostatic function of platelets and it has been suggested that loss of this glycoprotein may occur during in vitro storage of platelet concentrates. In this study two quantitative radioimmunoassays were developed to measure the content of glycoprotein Ib in platelets stored under a range of conditions used in blood banks. One assay involved the use of iodinated Maclura pomifera lectin and the other the binding of a monoclonal antibody (AN51) specific for glycoprotein Ib. The results showed that there was no significant reduction in the glycoprotein Ib content of platelets under the storage conditions used. These results suggest that any loss of haemostatic effectiveness which occurs on in vitro storage of platelet concentrates is not attributable to a selective loss of glycoprotein Ib from the platelet surface.


HLA-E and immunobiology of pregnancy.
Recently, it has been suggested that non-classical antigens such as human leukocyte antigen (HLA)-G and HLA-E may interact with KIR receptors of NK cells which results into downregulation of immune response and helps in the maintenance of pregnancy. In the present study, we have investigated HLA-E polymorphism in normal fertile women and recurrent spontaneous aborters to assess the effect of HLA-E alleles on the success of pregnancy. Allele E*0101 was found to be significantly higher in patients with recurrent spontaneous abortion (chi(2) = 4.097 and P = 0.0430). Differential expression, peptide affinity, and stability of E*0101 may be one of the reasons.


Cytotoxic 5-aryl-1-(4-nitrophenyl)-3-oxo-1,4-pentadienes mounted on alicyclic scaffolds.
The 5-aryl-1-(4-nitrophenyl)-3-oxo-1,4-pentadienyl pharmacophore was incorporated into four series of compounds 1-4. Compounds 1a-g comprised a cluster of 3-arylidene-1-(4-nitrophenylmethylene)-2-oxo-3,4-dihydro-1H-naphthalenes while the analogues 2a-g consisted of a group of 6-arylidene-2-(4-nitrophenylmethylene)cyclohexanones. Three other compounds prepared in this study were 1-(4-nitrophenylmethylene)-3-(3,4,5-trimethoxyphenylmethylene)-2-oxo-2,3-dihydro-1H-indene 3a as well as two 5-arylidene-2-(4-nitrophenylmethylene)cyclopentanones 4a,b. The compounds were evaluated against human Molt 4/C8 and CEM T-lymphocytes as well as murine L1210 cells. In general, the compounds in series 1 displayed marked cytotoxicity having IC50 values in the 1-5 microM range while the related cyclohexyl analogues in series 2 were slightly less potent (IC50 figures were mainly 5-10 microM). The relative locations of two aryl rings present in all four series were considered to contribute significantly to bioactivity and may have accounted for the virtual absence of cytotoxic properties in series 3 and 4. Most of the compounds were administered intraperitoneally to mice using doses up to and including 300 mg/kg. No mortalities were noted. The inhibiting effect of most of the compounds towards Helicobacter pylori is noteworthy. The modes of action of representative compounds include the induction of apoptosis while some compounds weakly inhibited tubulin polymerisation and human N-myristoyltransferase.


Maxillary tuberosities size and shape in African Blacks total edentulous.
The manufacturing of impression standardized trays adapted to Blacks total edentulous patients is necessary. This study in complement to previous ones quantified maillary tuberosity size and shape in a sample of Ivory Coast population a very melting pot example in Africa. Hundred maxillary complete edentulous casts issuing from impressions with Schreinemakers trays adjusted or not with thermoplastic materials. The two tuberosities for each cast were marked and measured. The mesiodistal, vestibulopalatal diameters and the vestibule heights measurements were computer-generated. Tubercles were not significantly different in the two sectors for the same cast. They were elliptical-shaped with the mesiodistal length superior to the vestibulopalatal width and they are higher than large. There was no statistical correlation between the data. These findings are independent from patients age and sex. Therefore it had been proposed three standardized impression trays prototypes adapted to African Blacks posterior palatal sector according to tuberosity size and shape. This specificity is relevant in prosthodontics since individualization of treatment leads to more effective treatment by working within the patient's arch from instead of making patients fit a single standard.


'Nature Knows No Boundaries': The Role of Nature Conservation in Peacebuilding.
Humanity is facing a biodiversity crisis. To solve environmental problems, we bring people from Israel, Jordan, and the Palestinian Authority to the same table. Conservation efforts are beneficial for all communities and facilitate constructive dialog across divides in conflict zones. This pleads for the integration of nature conservation into peacebuilding interventions.


Effects of diameter, length, and circuit pressure on sound conductance through endotracheal tubes.
We evaluated the acoustic frequency response of endotracheal tubes (ETs) to assess their effect on respiratory system sound transmission studies. White noise 150-3300 Hz was introduced into 4.0-, 6.0-, and 8.0-mm ETs and recorded at their proximal and distal ends. Four tubes of each size were studied at their original and normalized lengths, in straight and bent configurations, and at circuit pressures from 0 to 20 cmH2O. The characteristics of the sound transmission were compared using an analysis of variance for repeated measures. The average transmission amplitude varied directly with tube diameter. The position of peaks and troughs on the amplitude frequency distribution depended on tube length but not on tube diameter. The angle of the phase-frequency plot correlated well with the length of the tube and was independent of its diameter. A 90 degrees bend in the tube had no effect on its sound transmission. Increasing the circuit pressure above ambient modified the frequency response only if volume changes occurred in the test lung. When used to conduct sound into the respiratory system an ET affects the incident signal predictably depending on its length and diameter but not on its curvature or circuit pressure.


A mutation in the leptin receptor is associated with Entamoeba histolytica infection in children.
Malnutrition substantially increases susceptibility to Entamoeba histolytica in children. Leptin is a hormone produced by adipocytes that inhibits food intake, influences the immune system, and is suppressed in malnourished children. Therefore we hypothesized that diminished leptin function may increase susceptibility to E. histolytica infection. We prospectively observed a cohort of children, beginning at preschool age, for infection by the parasite E. histolytica every other day over 9 years and evaluated them for genetic variants in leptin (LEP) and the leptin receptor (LEPR). We found increased susceptibility to intestinal infection by this parasite associated with an amino acid substitution in the cytokine receptor homology domain 1 of LEPR. Children carrying the allele for arginine (223R) were nearly 4 times more likely to have an infection compared with those homozygous for the ancestral glutamine allele (223Q). An association of this allele with amebic liver abscess was also determined in an independent cohort of adult patients. In addition, mice carrying at least 1 copy of the R allele of Lepr were more susceptible to infection and exhibited greater levels of mucosal destruction and intestinal epithelial apoptosis after amebic infection. These findings suggest that leptin signaling is important in mucosal defense against amebiasis and that polymorphisms in the leptin receptor explain differences in susceptibility of children in the Bangladesh cohort to amebiasis.


Developmental impact of air pollution on brain function.
Air pollution is an important contributor to the global burden of disease, particularly to respiratory and cardiovascular diseases. In recent years, evidence is accumulating that air pollution may adversely affect the nervous system as shown by human epidemiological studies and by animal models. Age appears to play a relevant role in air pollution-induced neurotoxicity, with growing evidence suggesting that air pollution may contribute to neurodevelopmental and neurodegenerative diseases. Traffic-related air pollution (e.g. diesel exhaust) is an important contributor to urban air pollution, and fine and ultrafine particulate matter (PM) may possibly be its more relevant component. Air pollution is associated with increased oxidative stress and inflammation both in the periphery and in the nervous system, and fine and ultrafine PM can directly access the central nervous system. This short review focuses on the adverse effects of air pollution on the developing brain; it discusses some characteristics that make the developing brain more susceptible to toxic effects, and summarizes the animal and human evidence suggesting that exposure to elevated air pollution is associated with a number of behavioral and biochemical adverse effects. It also discusses more in detail the emerging evidence of an association between perinatal exposure to air pollution and increased risk of autism spectrum disorder. Some of the common mechanisms that may underlie the neurotoxicity and developmental neurotoxicity of air pollution are also discussed. Considering the evidence presented in this review, any policy and legislative effort aimed at reducing air pollution would be protective of children's well-being.


[Level of evidence for therapeutic drug monitoring for docetaxel].
Pharmacokinetic properties of docetaxel, an anticancer drug, are though to be interesting for therapeutic drug monitoring: high inter- and intra-variability, relationship between exposure and efficacy and especially toxicity. Moreover, the 3-weekly administration, which is the more effective scheme, is also the more toxic. However, neutropenia can be modeled and be efficiently predicted without needing plasma drug concentrations. The level evidence of therapeutic drug monitoring is thus weak regarding the possibility to adapt dose regimen without drug concentrations.


Picropodophyllin causes mitotic arrest and catastrophe by depolymerizing microtubules via insulin-like growth factor-1 receptor-independent mechanism.
Picropodophyllin (PPP) is an anticancer drug undergoing clinical development in NSCLC. PPP has been shown to suppress IGF-1R signaling and to induce a G2/M cell cycle phase arrest but the exact mechanisms remain to be elucidated. The present study identified an IGF-1-independent mechanism of PPP leading to pro-metaphase arrest. The mitotic block was induced in human cancer cell lines and in an A549 xenograft mouse but did not occur in normal hepatocytes/mouse tissues. Cell cycle arrest by PPP occurred in vitro and in vivo accompanied by prominent CDK1 activation, and was IGF-1R-independent since it occurred also in IGF-1R-depleted and null cells. The tumor cells were not arrested in G2/M but in mitosis. Centrosome separation was prevented during mitotic entry, resulting in a monopolar mitotic spindle with subsequent prometaphase-arrest, independent of Plk1/Aurora A or Eg5, and leading to cell features of mitotic catastrophe. PPP also increased soluble tubulin and decreased spindle-associated tubulin within minutes, indicating that it interfered with microtubule dynamics. These results provide a novel IGF-1R-independent mechanism of antitumor effects of PPP.


trans activation of type 1 interferon promoters by simian virus 40 T antigen.
A human transient expression system was used to measure the influence of simian virus 40 T antigen and adenovirus E1a proteins on the activation of alpha interferon subtype 1 (IFN-alpha 1) and IFN-beta promoters linked to the reporter chloramphenicol acetyltransferase gene. Large T-antigen production, amplified by expression plasmid replication in transfected 293 cells, was able to trans activate the IFN-beta promoter 5- to 10-fold, increasing both the constitutive and Sendai virus-induced levels of expression. Surprisingly, the previously quiescent transfected IFN-alpha 1 promoter in T-antigen-expressing cells displayed a level of inducibility similar to IFN-beta. The endogenous IFN-alpha 1 gene was also inducible to a limited extent in cells expressing T antigen. A truncated IFN-beta promoter deleted to position -37 relative to the CAP site was neither inducible nor trans activated by T antigen, suggesting that sequences required for efficient induction were also needed for trans activation. Since 293 cells express adenoviral E1a proteins, experiments were also performed in HeLa cells to assess the relative contribution of T antigen and E1a proteins to IFN trans activation. In HeLa cells, T-antigen coexpression increased the constitutive level of IFN-beta and IFN-alpha 1 promoter activity without augmenting relative inducibility. Coexpression of T antigen and E1a proteins did not have a cooperative effect on type 1 IFN expression.


[Abnormal gas collections in the abdomen in infants].
Many unusual and uncommon abnormal gas collections within the abdomen may be encountered. This paper reviews the reported causes for unusual gas collections in the abdomen and describes several new causes of abnormal bowel gas collections.


Commensal bacteria and MAMPs are necessary for stress-induced increases in IL-1β and IL-18 but not IL-6, IL-10 or MCP-1.
Regular interactions between commensal bacteria and the enteric mucosal immune environment are necessary for normal immunity. Alterations of the commensal bacterial communities or mucosal barrier can disrupt immune function. Chronic stress interferes with bacterial community structure (specifically, α-diversity) and the integrity of the intestinal barrier. These interferences can contribute to chronic stress-induced increases in systemic IL-6 and TNF-α. Chronic stress, however, produces many physiological changes that could indirectly influence immune activity. In addition to IL-6 and TNF-α, exposure to acute stressors upregulates a plethora of inflammatory proteins, each having unique synthesis and release mechanisms. We therefore tested the hypothesis that acute stress-induced inflammatory protein responses are dependent on the commensal bacteria, and more specifically, lipopolysaccharide (LPS) shed from Gram-negative intestinal commensal bacteria. We present evidence that both reducing commensal bacteria using antibiotics and neutralizing LPS using endotoxin inhibitor (EI) attenuates increases in some (inflammasome dependent, IL-1 and IL-18), but not all (inflammasome independent, IL-6, IL-10, and MCP-1) inflammatory proteins in the blood of male F344 rats exposed to an acute tail shock stressor. Acute stress did not impact α- or β- diversity measured using 16S rRNA diversity analyses, but selectively reduced the relative abundance of Prevotella. These findings indicate that commensal bacteria contribute to acute stress-induced inflammatory protein responses, and support the presence of LPS-mediated signaling in stress-evoked cytokine and chemokine production. The selectivity of the commensal bacteria in stress-evoked IL-1β and IL-18 responses may implicate the inflammasome in this response.


The natural history of herpes simplex virus infection of mother and newborn.
The controlled evaluation of vidarabine as therapy of neonatal herpes implex virus (HSV) infection provided an opportunity to collect data to further assess the natural history of maternal and newborn infections. Women delivering infected babies were young, nulliprous, and infrequent aborters. Nearly 50% of the gestations ended in premature labor. Maternal infection was asymptomatic in 39 of 56 (70%) of the mothers, at the time of delivery. However, risk factors included a past history of genital herpes at any time and exposure to a sexual partner with presumed HSV lesions. Associated diseases in children born to these women were common. Premature infants had an incidence of respiratory distress of 52% (14 of 27). Eight of 29 (28%) term newborns had a bacterial infection, antedating the onset of neonatal HSV infection. Virologic studies on infected newborns confirmed that skin lesions were the most frequent site for virus retrieval. Progression of disease from isolated skin lesions was common, occurring in 70% of babies whose presenting sign was skin vesicles. CSF was virus-positive from 14 babies and more frequently in those with localized CNS disease. Importantly, brain biopsy was necessary for diagnosis in four cases. Finally, neither the presence or absence of antibodies to HSV was useful in predicting either presentation or outcome of infection. These studies further emphasize the complex nature of HSV infections of the newborn and need for tertiary care.


Variable budgeting for staffing. Analysis and evaluation.
A successful resource-management system must be based on variable budgeting principles to account for fluctuation in patient census, methodically prepared through historical analysis of operations, carefully executed and monitored by accountable multidisciplinary managers. Significant attention must be paid to communication, positioning and stability of the patient care organization.


Tests of prolactin secretion in the diagnosis of hyperprolactinemic states: nomifensine and domperidone.
Forty-one subjects with hyperprolactinemia underwent testing on separate occasions with nomifensine, an indirectly acting dopamine agonist, and domperidone, a dopamine receptor-blocking agent. Nomifensine (200 mg orally) did not significantly modify plasma levels of prolactin (PRL) in 17 subjects in whom the existence of a pituitary tumor had been established at surgery (12 subjects) or was highly probable (5 subjects). Of the remaining 24 patients with hyperprolactinemia of uncertain etiology, 6 had PRL responsiveness to nomifensine (decrease of baseline PRL levels greater than or equal to 30%) and 18 had PRL unresponsiveness to the drug. The administration of domperidone (4-mg bolus injected intravenously) showed in 36 of the 41 patients the existence of a homogeneity between PRL responsiveness to nomifensine and PRL responsiveness to domperidone. In only five patients was failure of nomifensine to lower plasma PRL levels associated with an increase in plasma PRL levels after domperidone administration (at least doubling of baseline PRL levels). The combined application of nomifensine and domperidone tests holds promise of being a useful method for distinguishing among hyperprolactinemic subjects those with a prolactinoma.


Pathway-Supporting Health Information Systems: A Review.
Care pathways and supporting health information systems (HIS) have been permeate the discipline of Health Information Systems Research (HISR) over years. Traditional objectives of workflow assistance are increasingly extended by interdisciplinary goals from technology, medicine, management and public health research. A systematic literature review is dedicated to this integrating character. It examines the interdisciplinary mesh of objectives associated with care pathways and pathway-supporting HIS in the HISR literature. From 47 identified articles, 6 thematic themes were derived. Their consolidation supports in particular design and development processes as it describes the solution space of future pathway-supporting HIS addressing requirements stated by multiple stakeholders.


[Methodology for the study of the regulation of body weight and/or the aetiology of obesity].
Obesity, one of the most serious health problems of developed societies, is the result of a positive energy balance maintained over time. The regulation of body weight and its maintenance seem to be regulated by an axis of three interdependent components: dietary intake, energy expenditure and adipogenesis, although it is necessary a deeper understanding of the processes involved in the oxidation of nutrients and in the energy balance. The metabolic processes are numerous and inter-related, it is however convenient to study them separately in such a way that it is possible to obtain a better knowledge of the complete system. Indeed, this is the procedure employed in the design of numerous experiments, be they on laboratory animals, cellular cultures, or even on human beings when the molecular mechanisms involved in the regulation of body weight are examined. Both in vitro methods (cellular and subcellular models) and in vivo ones have made it possible to increase knowledge of the mechanisms that control body weight. It is worth underlining the new strategies that the molecular era and provides us with, although the techniques that consider the human organism as a whole might have a notable influence on the development of new drugs, together with therapeutic management and the prevention of obesity.


The role of vitamin supplementation in the prevention of cardiovascular disease events.
The production, sale, and consumption of multiple vitamins is a multibillion-dollar industry. Most Americans take some form of supplement ostensibly for prevention of cardiovascular disease. It has been claimed that vitamin A retards atherogenesis. Vitamin C is an antioxidant and is thought to possibly decrease free radical-induced endothelial injury, which can lead to atherosclerotic plaque formation. Vitamin E has been extensively studied for its possible effects on platelet function as well as inhibition of foam-cell formation. Low levels of vitamin D have been thought to negatively impact myocardial structure and increase the risk for cardiovascular events. Increased intake of vitamin B6, B12, and folate has been associated with reduction of homocysteine levels; elevated homocysteine blood levels have been associated with the occurrence of stroke, heart attack, and cardiovascular death. The purpose of this study was to review the currently available literature for vitamin supplementation with respect to prevention of cardiovascular disease. Unfortunately, the current evidence suggests no benefit exists with vitamin supplementation in the general US population. Further research is needed to evaluate whether there are specific populations that might benefit from vitamin supplementation.


Complex mate searching in the satin bowerbird Ptilonorhynchus violaceus.
Mate-choice studies typically focus on male traits affecting female mating decisions, but few studies seek to identify the behavioral rules females use when searching for mates. Current models suggest that females may either directly compare a set of males ("pooled comparison") or compare each male to an internal standard ("sequential-search rule") when judging the suitability of potential mates. Models also differ in other specific aspects, such as the predicted number of sampling bouts initiated and the tendency of females to return to males after previous visits. We monitored 63 female satin bowerbirds, Ptilonorhynchus violaceus, during mate sampling to reconstruct their search patterns. We found that females typically sampled several males and returned to the most attractive male for mating: a behavior consistent with the pooled-comparison tactic. Females, however, varied in the number of males sampled; some visited only one male before mating. We found that this variation can be explained by differences among females in the number of mates, the date mate searching is initiated, and long-term experience with males. Further, females were observed to initiate two distinct sampling bouts, with the rejection of most of their potential mates occurring before the start of the second sampling bout. This suggests that the choices of potential mates are narrowed prior to the second sampling bout and that the later visits may function to reconsider preliminary decisions made during the first sampling bout or to resolve decisions concerning the remaining potential mates. Our results indicate that mate searching is a complex process in which females use multiple sampling bouts to find suitable mates and in which several different factors influence their search behavior.


Neonatal cytomegalovirus infections: the relative role of neonatal blood transfusion and maternal exposure.
A prospective study of premature infants admitted to an intensive care neonatal unit was undertaken to evaluate the relative role of blood transfusions and maternal exposure in infections caused by cytomegalovirus (CMV), varicella zoster virus (VZV) and herpes simplex virus (HSV). During the first year of life, 13.7%, 4.8% and 4% of the infants became infected with CMV, VZV and HSV, respectively, as determined by virus isolation or seroconversion. Transfusion in the newborn period did not influence the rates of VZV or HSV infections. A higher rate of CMV infections occurred in transfused (18.8%) than in non-transfused (11%) infants but the difference was not statistically significant. A significant correlation was found between maternal antibody titers and the rate of CMV infection in infants whether or not transfusion occurred. An even stronger association was found between breast feeding and CMV infections. The risk of alloimmunization to erythrocyte and leucocyte antigens was also assessed; no evidence of increased alloimmunization to these antigens was associated with transfusion.


Folate status of the population in the Canadian Health Measures Survey.
Low folate concentrations are inversely associated with birth defects, including neural tube defects, congenital heart disease and oral clefts. Conversely, high folate concentrations may be associated with adverse outcomes, including increased risk of colorectal cancer among those with pre-existing neoplasms. The purpose of our study was to investigate the folate status of a nationally representative sample of Canadians, including a subset of women of childbearing age. We examined red blood cell folate concentrations among members of the general population aged 6-79 years (n = 5248) and separately among women of childbearing age (15-45 yr, n = 1162), as recorded by the Canadian Health Measures Survey and measured by immunologic assay. We assessed the data for significant differences by age, sex and socioeconomic status. Less than 1% of Canadians showed folate deficiency (red blood cell folate < 305 nmol/L) and 40% showed high folate concentrations (> 1360 nmol/L). Among women of childbearing age, 22% showed concentrations below those considered optimal for maximal neural tube defect-risk reduction (< 906 nmol/L). Significant differences by age and socio-economic status, but not sex, were evident in median red blood cell folate concentrations, although concentrations in all groups exceeded recommended levels. No differences by age or income were found among women of child-bearing age. Folate deficiency is virtually nonexistent in the Canadian population, although high folate concentrations are evident. Additional research is needed to better understand the determinants of red blood cell folate among women of childbearing age who have concentrations below levels that are maximally protective against neural tube defects. Ongoing monitoring of the folate status of Canadians and the relationship between red blood cell folate and health outcomes is warranted.


Lupus headaches in childhood-onset systemic lupus erythematosus: relationship to disease activity as measured by the systemic lupus erythematosus disease activity index (SLEDAI) and disease damage.
The Systemic Lupus Erythematosus Disease Activity Index (SLEDAI) is the most commonly used measure of disease activity for children with systemic lupus erythematosus (SLE). For headaches to be scored in the SLEDAI as a symptom of active disease, they have to be nonresponsive to narcotic analgesia. This may affect the overall estimation of disease activity, especially because headaches are common among children with SLE and narcotic analgesia is rarely used for headache therapy in paediatrics. Moreover, the importance of headaches for the development of damage and their relation to other clinical parameters and outcomes has not been well described for children with SLE. We reviewed the medical charts of an inception cohort of children (n = 63) who were newly diagnosed with SLE. Information on headaches and other disease parameters was obtained. Disease activity and damage were measured using the SLEDAI and the Systemic Lupus International Collaboration Clinics/American College of Rheumatology Damage Index (SDI), respectively. It has been shown that the accumulated burden of active disease as measured by serial SLEDAI scores over time is one of the best predictors of eventual damage to children with SLE. New-onset or significant increase of severe and/or persistent headaches (LHA) were reported in 43% of the patients during a mean follow-up of 3.6 years. LHA occurred preferentially among patients with elevated levels of antiphospholipid antibodies (aPL) (P < 0.02) and only 6% of all LHA episodes were treated with narcotics and thus considered for the measurement of disease activity in the SLEDAI. LHA were unrelated to proxy-measures of disease activity, such as the need to intensify therapies. When used in children, the insensitivity of the SLEDAI to capture LHA did not seem to decrease the responsiveness of the SLEDAI to detect clinically important worsening of disease, or negatively impact on its ability to predict damage.


Multiple primary lung cancer: a rising challenge.
With the use of high-resolution chest imaging system and lung cancer screening program, patients with multiple primary lung cancers (MPLCs) are becoming a growing population in clinical practice worldwide. The diagnostic criteria for MPLCs has been established and modified by three major lung cancer research institutes. However, due to the fact that the differential diagnosis between MPLCs and a recurrence, metastatic, or satellite lesion arising from the original lesion remains ambiguous and confusing, there is still insufficient evidence to support a uniform guideline. Newly developed molecular and genomic methods have the potential to better define the relationship among multiple lesions and bring the possibility of targeted therapy. Surgical resection remains the first choice for the treatment of MPLCs and detailed strategy should be carefully planned taking characteristics of the tumor and status of patients into consideration. For those who are intolerant to surgery, a new technology called stereotactic body radiation therapy (SBRT) is now an optional therapeutic strategy. Furthermore, multiple GGOs are unique MPLCs that need special attentions in the clinical practice.


A survey of registered nursing homes in Edinburgh.
Between February and November 1984, 18 registered nursing homes in Edinburgh were visited and information was obtained about their 400 patients. Details of the facilities provided by these homes are presented here. Admission and biographical details were obtained for each patient and the dependency of the nursing home population was determined; 28% of the total population appeared to be independent in self-care, though there were large variations between homes. Forty-two patients (10.5%) were found to be receiving Department of Health and Social Security supplementary benefit. The characteristics of this group are compared with those of the rest of the nursing home population. The implications of these observations and recent legislative developments are discussed.


Bone material properties and mineral matrix contributions to fracture risk or age in women and men.
The strength of bone is related to its mass and geometry, but also to the physical properties of the tissue itself. Bone tissue is composed primarily of collagen and mineral, each of which changes with age, and each of which can be affected by pharmaceutical treatments designed to prevent or reverse the loss of bone. With age, there is a decrease in collagen content, which is associated with an increased mean tissue mineralization, but there is no difference in cross-link levels compared to younger adult bone. In osteoporosis, however, there is a decrease in the reducible collagen cross-links without an alteration in collagen concentration; this would tend to increase bone fragility. In older people, the mean tissue age (MTA) increases, causing the tissue to become more highly mineralized. The increased bone turnover following menopause may reduce global MTA, and would reduce overall tissue mineralization. Bone strength and toughness are positively correlated to bone mineral content, but when bone tissue becomes too highly mineralized, it tends to become brittle. This reduces its toughness, and makes it more prone to fracture from repeated loads and accumulated microcracking. Most approved pharmaceutical treatments for osteoporosis suppress bone turnover, increasing MTA and mineralization of the tissue. This might have either or both of two effects. It could increase bone volume from refilling of the remodeling space, reducing the risk for fracture. Alternatively, the increased MTA could increase the propensity to develop microcracks, and reduce the toughness of bone, making it more likely to fracture. There may also be changes in the morphology of the mineral crystals that could affect the homogeneity of the tissue and impact mechanical properties. These changes might have large positive or negative effects on fracture incidence, and could contribute to the paradox that both large and small increases in density have about the same effect on fracture risk. Bone mineral density measured by DXA does not discriminate between density differences caused by volume changes, and those caused by changes in mineralization. As such, it does not entirely reflect material property changes in aging or osteoporotic bone that contribute to bone's risk for fracture.


Venezuelan encephalitis emergence mediated by a phylogenetically predicted viral mutation.
RNA viruses are notorious for their genetic plasticity and propensity to exploit new host-range opportunities, which can lead to the emergence of human disease epidemics such as severe acute respiratory syndrome, AIDS, dengue, and influenza. However, the mechanisms of host-range change involved in most of these viral emergences, particularly the genetic mechanisms of adaptation to new hosts, remain poorly understood. We studied the emergence of Venezuelan equine encephalitis virus (VEEV), an alphavirus pathogen of people and equines that has had severe health and economic effects in the Americas since the early 20th century. Between epidemics, VEE disappears for periods up to decades, and the viral source of outbreaks has remained enigmatic. Combined with phylogenetic analyses to predict mutations associated with a 1992-1993 epidemic, we used reverse genetic studies to identify an envelope glycoprotein gene mutation that mediated emergence. This mutation allowed an enzootic, equine-avirulent VEEV strain, which circulates among rodents in nearby forests to adapt for equine amplification. RNA viruses including alphaviruses exhibit high mutation frequencies. Therefore, ecological and epidemiological factors probably constrain the frequency of VEE epidemics more than the generation, via mutation, of amplification-competent (high equine viremia) virus strains. These results underscore the ability of RNA viruses to alter their host range, virulence, and epidemic potential via minor genetic changes. VEE also demonstrates the unpredictable risks to human health of anthropogenic changes such as the introduction of equines and humans into habitats that harbor zoonotic RNA viruses.


Complex Behavior in the Dynamics of a Polymeric Biocomposite Material-"Liquid Wood". Experimental and Theoretical Aspects.
The purpose of the present paper is to analyze, both experimentally and theoretically, the behavior of the polymeric biocomposite generically known as "liquid wood", trademarked as Arbofill. The experimental part refers to the mechanical performance in tension and compression, having as finality the possibility of using "liquid wood" as a material suitable for the rehabilitation of degraded wooden elements in civil structures (ex. use in historical buildings, monuments etc.). The theoretical part refers to computer simulations regarding the mechanical behavior of "liquid wood" as well as to a theoretical model in the paradigm of motion, which describes the same behavior. This model is based on the hypothesis that "liquid wood" can be assimilated, both structurally and functionally, to a multifractal object, situation in which its entities are described through continuous, non-differentiable curves. Then, descriptions of the behavior of "liquid wood", both in the Schrödinger-type and in hydrodynamic-type representations at various scale resolutions, become operational. Since in the hydrodynamic-type representation, the constitutive law of "liquid wood" can be highlighted, several operational procedures (Ricatti-type gauge, differential geometry in absolute space etc.) will allow correlations between the present proposed model and the experimental data. The obtained results, both practical (81% bearing capacity in compression and 36% bearing capacity in tension, compared to control samples) and theoretical (validation of material performance in virtual environment simulations, stresses and strains correlations in a theoretical model) indicate that "liquid wood" could be used in the construction industry, as a potential rehabilitation material, but with more development clearly needed.


Botryosphaeriaceae associated with Acacia heterophylla (La Réunion) and Acacia koa (Hawaii).
Acacia koa and A. heterophylla are commonly occurring native trees on the Hawaiian Islands and La Réunion, respectively. A recent phylogenetic study suggested that A. heterophylla renders A. koa paraphyletic, and that the former likely arose from the Hawaiian Islands around 1.4 million years ago. An intriguing question is whether their microbiota is similar, although they occur naturally in two very distant geographical locations. In this study, we compared the fungi in the Botryosphaeriaceae isolated from natural populations of A. koa and A. heterophylla. These fungi were chosen because they commonly occur on woody plants and some are important pathogens. They are also known to have been moved globally on asymptomatic plant materials. Isolates were identified based on comparisons of DNA sequence data for the rDNA-ITS, TEF1-α and β-tubulin loci. Ten Botryosphaeriaceae species were identified, of which four species were specific to A. koa from the Hawaiian Islands and five to A. heterophylla in La Réunion. Only one species, Neofusicoccumparvum, which is known to have a wide global distribution, was common to both hosts. The overall results of this study suggest that although A. koa and A.heterophylla share a recent evolutionary history, they have established independent microbiota, at least in terms of the Botryosphaeriaceae.


Mycoplasma pneumoniae carriage in children with recurrent respiratory tract infections is associated with a less diverse and altered microbiota.
Mycoplasma pneumoniae is a common cause of community-acquired pneumonia in school-aged children and can be preceded by asymptomatic carriage. However, its role in recurrent respiratory tract infections is unclear. We studied the prevalence of M.pneumoniae carriage in children with recurrent respiratory infections and identified associated factors. We tested M.pneumoniae carriage by qPCR in children with recurrent infections and their healthy family members in a cross-sectional study. Serum and mucosal total and M.pneumoniae-specific antibody levels were measured by ELISA and nasopharyngeal microbiota composition was characterized by 16S-rRNA sequencing. Prevalence of M.pneumoniae carriage was higher in children with recurrent infections (68%) than their family members without infections (47% in siblings and 27% in parents). M.pneumoniae carriage among family members appeared to be associated with transmission within the household, likely originating from the affected child. In logistic regression corrected for age and multiple comparisons, IgA (OR 0.16 [0.06-0.37]) and total IgG deficiency (OR 0.15 [0.02-0.74]) were less prevalent in M.pneumoniae carriers (n = 78) compared to non-carriers (n = 36). In multivariable analysis, the nasopharyngeal microbiota of M.pneumoniae carriers had lower alpha diversity (OR 0.27 [0.09-0.67]) and a higher abundance of Haemophilus influenzae (OR 45.01 [2.74-1608.11]) compared to non-carriers. M.pneumoniae carriage is highly prevalent in children with recurrent infections and carriers have a less diverse microbiota with an overrepresentation of disease-associated microbiota members compared to non-carriers. Given the high prevalence of M.pneumoniae carriage and the strong association with H. influenzae, we recommend appropriate antibiotic coverage of M.pneumoniae and H. influenzae in case of suspected pneumonia in children with recurrent respiratory tract infections or their family members. Wilhelmina Children's Hospital Research Fund, 'Christine Bader Stichting Irene KinderZiekenhuis', Sophia Scientific Research Foundation, ESPID Fellowship funded by Seqirus, Hypatia Fellowship funded by Radboudumc and The Netherlands Organisation for Health Research and Development (ZonMW VENI grant to LM Verhagen).


Ursolic acid-downregulated long noncoding RNA ASMTL-AS1 inhibits renal cell carcinoma growth via binding to HuR and reducing vascular endothelial growth factor expression.
It has been reported ursolic acid (UA), one of the naturally abundant pentacyclic triterpenes, possesses a wide range of biological activities including anti-inflammatory, anti-atherosclerotic, and anticancer properties. Renal cell carcinoma (RCC) is a severe malignancy due to its asymptomatically spreading ability. Our study aimed to investigate the role and molecular mechanism of UA in RCC. RCC cell proliferation, migration, invasion, and angiogenesis were assessed using 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide, Transwell, and tube formation assays. Xenograft tumor models were established to confirm the role of UA and long noncoding RNA ASMTL antisense RNA 1 (ASMTL-AS1) in vivo. Expression levels of ASMTL-AS1 and vascular endothelial growth factor (VEGF) were measured using reverse transcriptase quantitative polymerase chain reaction and western blot analysis. The interaction probabilities of ASMTL-AS1 or VEGF with RNA-binding protein human antigen R (HuR) were verified by RNA immunoprecipitation experiment. The half-life period of messenger RNA (mRNA) was determined using actinomycin D. UA inhibited RCC cell growth in vivo and tumorigenesis in vitro. ASMTL-AS1 was highly expressed in RCC cell lines. Of note, UA downregulated ASMTL-AS1 expression, and overexpressed ASMTL-AS1 reversed the UA-induced suppression on RCC cell migration, invasion, and tube formation. Additionally, ASMTL-AS1 bound to HuR to maintain the stability of VEGF mRNA. Rescue experiments showed that the suppressed malignancy of RCC cells mediated by ASMTL-AS1 knockdown was counteracted by overexpression of VEGF. Moreover, silenced ASMTL-AS1 inhibited RCC tumor growth and metastasis in vivo. The obtained data suggest UA as a promising therapeutic agent to attenuate the development of RCC via regulation of the targeted molecules.


CytoNorm: A Normalization Algorithm for Cytometry Data.
High-dimensional flow cytometry has matured to a level that enables deep phenotyping of cellular systems at a clinical scale. The resulting high-content data sets allow characterizing the human immune system at unprecedented single cell resolution. However, the results are highly dependent on sample preparation and measurements might drift over time. While various controls exist for assessment and improvement of data quality in a single sample, the challenges of cross-sample normalization attempts have been limited to aligning marker distributions across subjects. These approaches, inspired by bulk genomics and proteomics assays, ignore the single-cell nature of the data and risk the removal of biologically relevant signals. This work proposes CytoNorm, a normalization algorithm to ensure internal consistency between clinical samples based on shared controls across various study batches. Data from the shared controls is used to learn the appropriate transformations for each batch (e.g., each analysis day). Importantly, some sources of technical variation are strongly influenced by the amount of protein expressed on specific cell types, requiring several population-specific transformations to normalize cells from a heterogeneous sample. To address this, our approach first identifies the overall cellular distribution using a clustering step, and calculates subset-specific transformations on the control samples by computing their quantile distributions and aligning them with splines. These transformations are then applied to all other clinical samples in the batch to remove the batch-specific variations. We evaluated the algorithm on a customized data set with two shared controls across batches. One control sample was used for calculation of the normalization transformations and the second control was used as a blinded test set and evaluated with Earth Mover's distance. Additional results are provided using two real-world clinical data sets. Overall, our method compared favorably to standard normalization procedures. The algorithm is implemented in the R package "CytoNorm" and available via the following link: www.github.com/saeyslab/CytoNorm © 2019 The Authors. Cytometry Part A published by Wiley Periodicals, Inc. on behalf of International Society for Advancement of Cytometry.


[Rotavirus infection in a maternity home based on virological and serological study data].
The studies carried out in a maternity house, employing a set of virological and serological methods, revealed the facts of introduction of rotavirus infection into the maternity house, and followed the further spread of the infection. Epidemiological surveys evaluated the sources of infection (parturients, newborns, medical personnel), means of spread of rotavirus infection, and analysed the epidemiological advantages of wards for mother and newborn baby staying together.


Quality of life following esophagectomy with three-field lymphadenectomy for carcinoma, focusing on its relationship to vocal cord palsy.
To clarify the quality of life of patients who underwent esophagectomy for carcinoma by right thoracotomy, laparotomy and cervical anastomosis, 116 patients who were cancer free at the time of mailing a questionnaire were analyzed. A significant decrease in vital capacity for 3 years postoperatively, as well as in the percentage of ideal body weight, between 3 and 5 years were observed in 57 patients with three-field lymphadenectomy. Patients' quality of life undergoing three-field dissection was worse than those with less radical lymphadenectomy (59 cases) in terms of the performance status and difficulty in talking at 60 months or more postoperatively. Around 20% of all patients reported severe hoarseness due to permanent recurrent nerve paralysis, resulting in poor quantity of food intake at 24 months or less postoperatively and restricted daily activity and difficulty in talking at 60 months or more after the operation. When a patient suffers from vocal cord insufficiency caused by permanent paralysis of the recurrent nerve, early treatment before discharge from the hospital should be performed to improve the quality of life of such a patient.


The role of age-related sleep EEG changes in memory decline: experiments and computational modeling.
The slow oscillation (SO) observed during deep sleep is known to facilitate memory consolidation. However, the impact of age-related changes in sleep electroencephalography (EEG) oscillations and memory remains unknown. In this study, we aimed to investigate the contribution of age-related changes in sleep SO and its role in memory decline by combining EEG recordings and computational modeling. Based on the detected SO events, we found that older adults exhibit lower SO density, lower SO frequency, and longer Up and Down state durations during N3 sleep compared to young and middle-aged groups. Using a biophysically detailed thalamocortical network model, we simulated the "aged" brain as a partial loss of synaptic connections between neurons in the cortex. Our simulations showed that the changes in sleep SO properties in the "aged" brain, similar to those observed in older adults, resulting in impaired memory consolidation. Overall, this study provides mechanistic insights into how age-related changes modulate sleep SOs and memory decline.Clinical Relevance- This study contributes towards finding feasible biomarkers and target mechanism for designing therapy in older adults with memory deficits, such as Alzheimer's disease patients.


Prevalence of dental fluorosis among 12-15-year-old students in Enugu Metropolis, Nigeria.
Excessive ingestion of fluoride during tooth development, particularly at the maturation stage, may result in dental fluorosis, with clinical implications. Literature is scarce on dental fluorosis in Enugu, Nigeria. The aim of this study was to assess the prevalence of dental fluorosis in Enugu, a major city in South East Nigeria. A multistage sampling technique was used to select a calculated sample of 400 students. A pretested interviewer-administered questionnaire was used to ascertain student's sociodemographic and related variables. The student participants were examined for dental fluorosis using Dean's index criteria according to the World Health Organization guidelines. Data were analyzed using SPSS version 16, and Chi-square test of association was used to compare proportions and ratios with significant level set at P < 0.05 and 95% confidence level. Among the 400 students analyzed, 231 (57.8%) and 169 (42.2%) were male and female, respectively. Mean age was 13.43 ± 1.021 years. The prevalence of dental fluorosis was 11.3%, with the preponderance of very mild score (82.2%), and no observed severe dental fluorosis. The difference in the distribution of the scores of fluorosis among the children was highly statistically significant (χ2 = 72.80, P = 0.000). Dental fluorosis was found present in 39 (10.3%) of 378 users of fluoridated toothpaste and in 6 (27.7%) of the 22 users of nonfluoridated toothpaste. The differences in the presence and absence of dental fluorosis were statistically significant among users of fluoridated toothpaste. This study shows the prevalence of dental fluorosis to be low among secondary school students of Enugu metropolis.


Genome activation by raspberry bushy dwarf virus coat protein.
Two sets of infectious cDNA clones of raspberry bushy dwarf virus (RBDV) have been constructed, enabling either the synthesis of infectious RNA transcripts or the delivery of infectious binary plasmid DNA by infiltration of Agrobacterium tumefaciens. In whole plants and in protoplasts, inoculation of RBDV RNA1 and RNA2 transcripts led to a low level of infection, which was greatly increased by the addition of RNA3, a subgenomic RNA coding for the RBDV coat protein (CP). Agroinfiltration of RNA1 and RNA2 constructs did not produce a detectable infection but, again, inclusion of a construct encoding the CP led to high levels of infection. Thus, RBDV replication is greatly stimulated by the presence of the CP, a mechanism that also operates with ilarviruses and alfalfa mosaic virus, where it is referred to as genome activation. Mutation to remove amino acids from the N terminus of the CP showed that the first 15 RBDV CP residues are not required for genome activation. Other experiments, in which overlapping regions at the CP N terminus were fused to the monomeric red fluorescent protein, showed that sequences downstream of the first 48 aa are not absolutely required for genome activation.


Paradigms on Immunotherapy Combinations with Chemotherapy.
Checkpoint inhibitors are being added to standard-of-care chemotherapy in multiple clinical trials. Success has been reported in non-small and small cell lung carcinomas and urothelial, head and neck, gastric, and esophageal cancers, and promising results are already available in triple-negative breast and pancreatic malignancies. The potential mechanisms of synergy include immunogenic tumor cell death, antiangiogenesis, selective depletion of myeloid immunosuppressive cells, and lymphopenia, which reduces regulatory T cells and makes room for proliferation of effector T cells. However, chemotherapy regimens have not been optimized for such combinations, perhaps explaining some recent clinical trial disappointments. Approaches to make the most of chemoimmunotherapy include neoadjuvant and adjuvant schemes.Significance: Immunotherapy of cancer based on PD-1/PD-L1 blockade has prompted a revolution in cancer clinical management. Evidence in phase III clinical trials already supports combinations of immunotherapy with standard-of-care chemotherapy for a number of malignant diseases. This review focuses on such evidence and provides an overview of the potential synergistic mechanisms of action and the opportunities to optimize chemoimmunotherapy regimens.


Identification of an anti-CRISPR protein that inhibits the CRISPR-Cas type I-B system in Clostridioides difficile.
Clostridioides difficile is the widespread anaerobic spore-forming bacterium that is a major cause of potentially lethal nosocomial infections associated with antibiotic therapy worldwide. Due to the increase in severe forms associated with a strong inflammatory response and higher recurrence rates, a current imperative is to develop synergistic and alternative treatments for C. difficile infections. In particular, phage therapy is regarded as a potential substitute for existing antimicrobial treatments. However, it faces challenges because C. difficile has highly active CRISPR-Cas immunity, which may be a specific adaptation to phage-rich and highly crowded gut environment. To overcome this defense, C. difficile phages must employ anti-CRISPR mechanisms. Here, we present the first anti-CRISPR protein that inhibits the CRISPR-Cas defense system in this pathogen. Our work offers insights into the interactions between C. difficile and its phages, paving the way for future CRISPR-based applications and development of effective phage therapy strategies combined with the engineering of virulent C. difficile infecting phages.


Generalized psychological distress among HIV-infected patients enrolled in antiretroviral treatment in Dilla University Hospital, Gedeo zone, Ethiopia.
Psychological disorders like depression and anxiety are potentially dangerous conditions. In the context of HIV/AIDS, this can influence health-seeking behavior or uptake of diagnosis and treatment for HIV/AIDS, add to the burden of disease for HIV patients, create difficulty in adherence to treatment, and increase the risk of mortality and morbidity. The objective of this study was to assess the prevalence and correlates of generalized psychological distress among HIV-infected subjects on antiretroviral treatment (ART). An institution-based cross-sectional study was conducted. Interviews were conducted with 500 patients initiating ART at Dilla Referral Hospital. Generalized psychological distress was measured using the Hospital Anxiety and Depression Scale (HADS). A cutoff score ≥19 was used to identify possible cases of patients with generalized psychological distress. Multivariable logistic regression analysis using SPSS Version 20 was performed to identify factors associated with psychological distress. The prevalence of generalized psychological distress among the population of this study was 11.2% (HADS≥19). Factors independently associated with generalized psychological distress were moderate stress (OR=6.87, 95% CI 2.27-20.81), low social support (OR=10.17, 95% CI 2.85-36.29), number of negative life events of six and above (OR=3.99, 95% CI 1.77-8.99), not disclosing HIV status (OR=5.24, 95% CI 1.33-20.62), and CD4 cell count of <200 cells/mm(3) (OR=1.98, 95% CI 0.45-0.83) and 200-499 cells/mm(3) (OR=3.53, 95% CI 1.62-7.73). This study provides prevalence of psychological distress lower than the prevalence of common mental disorders in Ethiopia and comparable to some other studies in sub-Saharan Africa. The findings are important in terms of their relevance to identifying high-risk groups for generalized psychological distress and preventing distress through integrating mental health services with HIV/AIDS care and support program.


Combining morphological and genomic evidence to resolve species diversity and study speciation processes of the Pallenopsis patagonica (Pycnogonida) species complex.
Pallenopsis patagonica (Hoek, 1881) is a morphologically and genetically variable sea spider species whose taxonomic classification is challenging. Currently, it is considered as a species complex including several genetic lineages, many of which have not been formally described as species. Members of this species complex occur on the Patagonian and Antarctic continental shelves as well as around sub-Antarctic islands. These habitats have been strongly influenced by historical large-scale glaciations and previous studies suggested that communities were limited to very few refugia during glacial maxima. Therefore, allopatric speciation in these independent refugia is regarded as a common mechanism leading to high biodiversity of marine benthic taxa in the high-latitude Southern Hemisphere. However, other mechanisms such as ecological speciation have rarely been considered or tested. Therefore, we conducted an integrative morphological and genetic study on the P. patagonica species complex to i) resolve species diversity using a target hybrid enrichment approach to obtain multiple genomic markers, ii) find morphological characters and analyze morphometric measurements to distinguish species, and iii) investigate the speciation processes that led to multiple lineages within the species complex. Phylogenomic results support most of the previously reported lineages within the P. patagonica species complex and morphological data show that several lineages are distinct species with diagnostic characters. Two lineages are proposed as new species, P. aulaeturcarum sp. nov. Dömel & Melzer, 2019 and P. obstaculumsuperavit sp. nov. Dömel, 2019, respectively. However, not all lineages could be distinguished morphologically and thus likely represent cryptic species that can only be identified with genetic tools. Further, morphometric data of 135 measurements showed a high amount of variability within and between species without clear support of adaptive divergence in sympatry. We generated an unprecedented molecular data set for members of the P. patagonica sea spider species complex with a target hybrid enrichment approach, which we combined with extensive morphological and morphometric analyses to investigate the taxonomy, phylogeny and biogeography of this group. The extensive data set enabled us to delineate species boundaries, on the basis of which we formally described two new species. No consistent evidence for positive selection was found, rendering speciation in allopatric glacial refugia as the most likely model of speciation.


Retraction: Developing and Testing Methylated Nano-Structured Dipeptides that Inhibit Src Kinase Activity In Vitro for Anti-Cancer Applications.
The article Developing and Testing Methylated Nano-Structured Dipeptides that Inhibit Src Kinase Activity In Vitro for Anti-Cancer Applications has been retracted by the journal due to authorship and reproducibility concerns.


Treatment outcomes of non-small cell lung cancers treated with EGFR tyrosine kinase inhibitors: a real-world cohort study.
Epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors (TKI) are a standard of care treatment options in non-small cell lung cancer (NSCLC). The present study investigated real-world EGFR TKI use and patient outcomes in NSCLC. We collected all the patients who had reimbursement for EGFR TKIs in Finland 2011-2020 and had data available at Finnish Cancer Registry. Survival and time-on-treatment (ToT) were analyzed from the first EGFR TKI purchase and patients were stratified according to the TKIs. Whole patient cohort consisted of 1498 individuals who were treated with erlotinib (n = 998), afatinib (n = 258), or gefitinib (n = 238). In the EGFR mutant cohort (all gefitinib users and afatinib users with non-squamous histology; n = 466), survival was comparable to registrational trials while patients treated with afatinib had improved survival (HR 0.67 CI 95% 0.53-0.85) and longer ToT (13.9 vs 11.9 months, NS) compared to those treated with gefitinib. Females treated with afatinib had improved survival (HR 0.61 CI 95% 0.44-0.83) and longer ToT (15.1 vs 12.5 months, NS) compared to gefitinib while similar was not observed in males. Later line osimertinib treatment was applied for 78 patients. Approximately 20% of the individuals treated with previous gefitinib or afatinib had later line osimertinib treatment. Efficacy analysis of osimertinib treated showed similar ToT and survival regardless of the first line EGFR TKI. EGFR mutants treated with afatinib have improved outcomes compared to gefitinib while later-line osimertinib was applied only for around 20% of the individuals. The study further highlights the good real-world performance of EGFR TKIs and sheds light on therapy sequencing.


Registered Nurses' Perceptions After a Patient with Ebola Virus Disease Is Admitted to Their Hospital.
Emerging diseases affect the nursing workforce, but little is known about the willingness of registered nurses (RNs) to work during outbreaks (eg, Ebola virus disease, COVID-19). The objective of our study was to examine the perceptions and attitudes of RNs in the United States regarding their duty to care and willingness to work after a patient infected with the Ebola virus was admitted to their hospital. We performed a quantitative, descriptive study using social media to recruit critical care RNs to complete an online survey. A total of 72 RNs completed the survey. While only 20 respondents reported providing direct care, more than half (n = 38) reported that family members asked them not to work with patients infected with the Ebola virus. A majority of respondents (n = 63) agreed that healthcare workers have a duty to help sick people despite high risks to themselves or their families; however, 59 agreed that family responsibilities would take priority. Respondents were less likely to work if their partners (n = 11) or children (n = 7) were ill but more likely to work if colleagues were infected (n = 48) or dying (n = 40). Shunning was experienced by 32 respondents, and 25 knew of others who were shunned. We observed several factors that affect RNs' willingness to provide care when patients are admitted, including moral conflict between their duty to treat sick people and their duty to protect their family. As part of infectious disease emergency planning, health policy managers should consider these complex factors, which may modulate effective patient care. While this study was limited to RNs in the United States during an Ebola virus disease outbreak, the results signal a need for similar research on other emerging infections such as COVID-19.


Loss of function of SLC25A46 causes lethal congenital pontocerebellar hypoplasia.
Disturbed mitochondrial fusion and fission have been linked to various neurodegenerative disorders. In siblings from two unrelated families who died soon after birth with a profound neurodevelopmental disorder characterized by pontocerebellar hypoplasia and apnoea, we discovered a missense mutation and an exonic deletion in the SLC25A46 gene encoding a mitochondrial protein recently implicated in optic atrophy spectrum disorder. We performed functional studies that confirmed the mitochondrial localization and pro-fission properties of SLC25A46. Knockdown of slc24a46 expression in zebrafish embryos caused brain malformation, spinal motor neuron loss, and poor motility. At the cellular level, we observed abnormally elongated mitochondria, which was rescued by co-injection of the wild-type but not the mutant slc25a46 mRNA. Conversely, overexpression of the wild-type protein led to mitochondrial fragmentation and disruption of the mitochondrial network. In contrast to mutations causing non-lethal optic atrophy, missense mutations causing lethal congenital pontocerebellar hypoplasia markedly destabilize the protein. Indeed, the clinical severity appears inversely correlated with the relative stability of the mutant protein. This genotype-phenotype correlation underscores the importance of SLC25A46 and fine tuning of mitochondrial fission and fusion in pontocerebellar hypoplasia and central neurodevelopment in addition to optic and peripheral neuropathy across the life span.


Narrow band imaging: clinical applications in oral and oropharyngeal cancer.
Narrow Band Imaging (NBI) is an endoscopic optical imaging enhancement technology that improves the contrast of mucosal surface texture, and enhances visualisation of mucosal and submucosal vasculature. White light is filtered to emit two 30-nm narrow bands of blue (415 nm) and green light (540 nm) light simultaneously, the former corresponding to the main peak absorption spectrum of haemoglobin, and the latter allowing visualisation of blood vessels in the deeper mucosal and submucosal layers. NBI has been used to better assess oral potentially malignant disorders (OPMD), identify oral and oropharyngeal squamous cell carcinoma (SCC), and to define surgical margins of head and neck malignancies. NBI shows great potential in improving detection rates of OPMD, facilitating better assessment of oral and oropharyngeal SCC, and reducing the risk of recurrence for oral SCC. Although further research is required to better understand and define intrapapillary capillary loop (IPCL) patterns and to relate these with clinical, histopathological and molecular parameters especially for early mucosal changes, there is building evidence to recommend its use as the new gold standard for endoscopic assessment in head and neck oncology.


The Snowman: A model of injuries and near-misses for the prevention of sharps injuries.
Sharps injuries (SI) and other blood/body fluid exposures (BBFE) present bloodborne pathogen risks for home healthcare (HHC) workers. While SI and BBFE are sufficiently frequent in HHC to be serious public health concerns, even moderately large surveys can still have insufficient power to identify risk factors. In this study, a new conceptual model for using near-misses for SI and BBFE was developed and its utility in statistical analyses of SI and BBFE risk factors was evaluated. A survey of HHC nurses (n = 787) and aides (n = 282) gathered data on the numbers of SI, BBFE, and near-misses in the past year. Questions focused on the circumstances leading up to the SI, BBFE, and near-misses. After evaluating the hypothesis that near-misses and events lie along the same causal pathway, we combined these outcomes to estimate their association with an important risk factor: employment status. There were similar frequencies of risk factors for the events SI, BBFE, and their near-misses, suggesting that they may share common causal pathways. Combined data on events and near-misses confirmed our hypothesis that part-time and temporary HHC aides were at higher risk than full-timers. Analyses combining injuries and near-misses may be useful in risk factor investigations.


Probability theory for 3-layer remote sensing in ideal gas law environment.
We extend the probability model for 3-layer radiative transfer [Opt. Express 20, 10004 (2012)] to ideal gas conditions where a correlation exists between transmission and temperature of each of the 3 layers. The effect on the probability density function for the at-sensor radiances is surprisingly small, and thus the added complexity of addressing the correlation can be avoided. The small overall effect is due to (a) small perturbations by the correlation on variance population parameters and (b) cancellation of perturbation terms that appear with opposite signs in the model moment expressions.


Progression of pediatric CKD of nonglomerular origin in the CKiD cohort.
Congenital anomalies of the kidney and urinary tract and genetic disorders cause most cases of CKD in children. This study evaluated the relationships between baseline proteinuria and BP and longitudinal changes in GFR in children with these nonglomerular causes of CKD. Urine protein-to-creatinine ratio, casual systolic and diastolic BP (normalized for age, sex, and height), and GFR decline were assessed in the prospective CKD in Children cohort study. A total of 522 children, median age 10 years (interquartile range, 7, 14 years) with nonglomerular CKD were followed for a median of 4.4 years. The mean baseline GFR in the cohort was 52 ml/min per 1.73 m(2) (95% confidence interval [95% CI], 50 to 54) and declined 1.3 ml/min per 1.73 m(2) per year on average (95%CI, 1.6 to 1.1). A 2-fold higher baseline urine protein-to-creatinine ratio was associated with an accelerated GFR decline of 0.3 ml/min per 1.73 m(2) per year (95% CI, 0.4 to 0.1). A 1-unit higher baseline systolic BP z-score was associated with an additional GFR decline of 0.4 ml/min per 1.73 m(2) per year (95% CI, 0.7 to 0.1). Among normotensive children, larger GFR declines were associated with larger baseline urine protein-to-creatinine ratios; eGFR declines of 0.8 and 1.8 ml/min per 1.73 m(2) per year were associated with urine protein-to-creatinine ratio <0.5 and ≥0.5 mg/mg, respectively. Among children with elevated BP, average GFR declines were evident but were not larger in children with higher levels of proteinuria. Baseline proteinuria and systolic BP levels are independently associated with CKD progression in children with nonglomerular CKD.


Interobserver reproducibility of the interpretation of I-123 FP-CIT single-photon emission computed tomography.
I-123 ioflupane (FP-CIT) single-photon emission computed tomography is a recognized tool in the diagnosis of Parkinsonian syndromes. In practice, data interpretation relies on visual and semiquantitative analyses. Good interobserver reproducibility is a prerequisite before claiming the robustness of a technique. This study aimed at evaluating interobserver reproducibility of this approach. Thirty nuclear medicine physicians participated in the study. Data included FP-CIT images and semiquantitative measurements of 12 cases, covering a wide spectrum of scintigraphic patterns and for which a 'true' clinical diagnosis based on long-term follow-up was available. Interobserver agreement was defined, for each case, as the highest percentage reached among the three proposed answers with complete agreement arbitrarily set at 80% or more. Variability in an individual observer's sensitivity to assess data as normal, equivocal or abnormal was scored using a three-point scale. Response rate was 99.7%. Among the three possible answers,'normal' accounted for 41.2% of the total, 'abnormal' for 49.8% and 'equivocal' for 8.1%. The mean interobserver agreement was 76% (range: 37-100%), with complete agreement being reached only in five cases. The interpretation proposed by most observers accorded to clinical diagnosis in 75% of the cases. Abnormalities of the central nervous system were encountered in all the cases with disagreement between the observer's interpretation and clinical diagnoses. An important variability in the observers' sensitivity was seen. In the particular setting of this preliminary study evaluating the reproducibility of FP-CIT single-photon emission computed tomography interpretation in a group of nuclear medicine physicians with various experiences, interobserver agreement was suboptimal. Collegial discussion and standardized interpretation criteria could contribute to an improved reproducibility.


Intestinal Regulatory T Cells as Specialized Tissue-Restricted Immune Cells in Intestinal Immune Homeostasis and Disease.
FOXP3+ regulatory T cells (Treg cells) are a specialized population of CD4+ T cells that restrict immune activation and are essential to prevent systemic autoimmunity. In the intestine, the major function of Treg cells is to regulate inflammation as shown by a wide array of mechanistic studies in mice. While Treg cells originating from the thymus can home to the intestine, the majority of Treg cells residing in the intestine are induced from FOXP3neg conventional CD4+ T cells to elicit tolerogenic responses to microbiota and food antigens. This process largely takes place in the gut draining lymph nodes via interaction with antigen-presenting cells that convert circulating naïve T cells into Treg cells. Notably, dysregulation of Treg cells leads to a number of chronic inflammatory disorders, including inflammatory bowel disease. Thus, understanding intestinal Treg cell biology in settings of inflammation and homeostasis has the potential to improve therapeutic options for patients with inflammatory bowel disease. Here, the induction, maintenance, trafficking, and function of intestinal Treg cells is reviewed in the context of intestinal inflammation and inflammatory bowel disease. In this review we propose intestinal Treg cells do not compose fixed Treg cell subsets, but rather (like T helper cells), are plastic and can adopt different programs depending on microenvironmental cues.


Laser explantation of a failing endosseous dental implant.
Explantation of failed dental implants has traditionally been performed by mechanical bone removal techniques. The advent of intraoral laser surgery has seen increasing numbers of applications in oral implantology. The technique demonstrates safe and efficient explantation of a failed dental implant using Er,Cr:YSGG laser. Laser assisted explantation of dental implants is a minimally invasive technique providing an alternative to conventional mechanical explantation techniques.


Variables that predict burnout in professional drivers.
Objectives. Stress maintained over time leads to a state of exhaustion known as burnout syndrome. This syndrome constitutes an occupational health problem, leading to high absenteeism. It can also mean that workers come to the workplace feeling unwell, which increases occupational collisions and injuries at work. In this study, we developed a predictive model of burnout in professional drivers using the following indicators: age, hours worked, seniority, educational level, fatigue, personality, attitudes toward driving, safety behaviors in the vehicle, and work characteristics and content. Method. A total of 523 professional drivers from different transport sectors, obtained through non-probability sampling, participated in the study. We used SPSS version 25.0 to analyze the data. Results. We determined the predictive capacity of certain variables that affect drivers and cause burnout. Exhaustion can be predicted with fatigue (48.8%), professional efficiency with emotional stability (39.8%) and cynicism with lack of motivation (28%) as the best predictors. Conclusions. The results contribute to a better knowledge of those factors that cause burnout in professional drivers. It is important to design individual interventions to reduce burnout, which would help reduce sick leave and possible collisions, in addition to providing greater well-being for drivers.


The moderating role of objective and subjective numeracy in attribute framing.
Previous research has found that objective numeracy moderates framing effects: People who are less numerate were found to be more susceptible to goal-framing and attribute-framing effects than people who are highly numerate. This study examined the possibility that subjective numeracy likewise moderates attribute framing in contexts where participants are presented with percentages of success or failure. The results show that compared with highly numerate participants, less numerate participants were more susceptible to the effect of attribute framing. Interestingly, this moderating effect was revealed only when using objective numeracy measures, and not when subjective numeracy measures were used. Future research is suggested to replicate these findings, to establish the generalizability of numeracy as a moderator of other cognitive biases, and to examine several possible theoretical explanations for the differential moderation of attribute-framing bias.


Characteristics of genetics-related news content in Black weekly newspapers.
BACKGROUND/AIMS/OBJECTIVES: The media are an important source of health information, especially for those with less access to regular health care. Black news outlets such as Black newspapers are a source of health information for African Americans. This study characterized media coverage of genetics-related information in Black weekly newspapers and general audience newspapers from the same communities. All health stories in a sample of 24 Black weekly newspapers and 12 general audience newspapers from January 2004 to December 2007 were reviewed for genetics-related stories. These stories were further coded for both journalistic and public health variables. Of all health-related stories identified, only 2% (n = 357) were considered genetics related. Genetics-related stories in Black newspapers - compared to those in general audience newspapers - were larger, more locally and racially relevant, and more likely to contain recommendations or action steps to improve health or reduce disease risks and to mention the importance of knowing one's family history. Stories in general audience newspapers were more likely to discuss causes of disease, mention genetic testing or therapy, and suggest a high/moderate degree of genetic determinism. Black newspapers are a viable communication channel to disseminate findings and implications of human genome research to African American audiences.


Determination of the concentrations of trilostane and ketotrilostane that inhibit ex vivo canine adrenal gland synthesis of cortisol, corticosterone, and aldosterone.
To determine whether trilostane or ketotrilostane is more potent in dogs and determine the trilostane and ketotrilostane concentrations that inhibit adrenal gland cortisol, corticosterone, and aldosterone secretion by 50%. 24 adrenal glands from 18 mixed-breed dogs. Adrenal gland tissues were sliced, placed in tissue culture, and stimulated with 100 pg of ACTH/mL alone or with 5 concentrations of trilostane or ketotrilostane. Trials were performed independently 4 times. In each trial, 6 samples (1 for each time point) were collected for each of the 5 concentrations of trilostane and ketotrilostane tested as well as a single negative control samples. At the end of 0, 1, 2, 3, 5, and 7 hours, tubes were harvested and media and tissue slices were assayed for cortisol, corticosterone, aldosterone, and potassium concentrations. Data were analyzed via pharmacodynamic modeling. One adrenal slice exposed to each concentration of trilostane or ketotrilostane was submitted for histologic examination to assess tissue viability. Ketotrilostane was 4.9 and 2.4 times as potent in inhibiting cortisol and corticosterone secretion, respectively, as its parent compound trilostane. For trilostane and ketotrilostane, the concentrations that inhibited secretion of cortisol or corticosterone secretion by 50% were 480 and 98.4 ng/mL, respectively, and 95.0 and 39.6 ng/mL, respectively. Ketotrilostane was more potent than trilostane with respect to inhibition of cortisol and corticosterone secretion. The data should be useful in developing future studies to evaluate in vivo serum concentrations of trilostane and ketotrilostane for efficacy in the treatment of hyperadrenocorticism.


Correlations between computation and experimental thermodynamics of halogen bonding.
Correlations between experimental, solution-phase thermodynamic data and calculated gas-phase energies of interaction are investigated for noncovalent halogen bonding interactions between electron-deficient iodo compounds and Lewis bases. The experimental data consist of free energies of interaction spanning roughly 7 kcal/mol; they encompass halogen bonds involving both organic (iodoperfluoroarene or iodoperfluoroalkane) and inorganic (I(2), IBr, ICN) donors with nitrogen- and oxygen-based acceptors and are divided into two sets according to the identity of the solvent in which they were determined (alkanes or CCl(4)). Adiabatic energies of halogen bonding were calculated using a variety of methods, including 22 DFT exchange-correlation functionals, using geometries optimized at the MP2/6-31+G(d,p) level of theory. Certain DFT functionals, particularly the B97-1, B97-2, and B98 family, provide outstanding linear correlations with the experimental thermodynamic data, as assessed by a variety of statistical methods.


Hip fracture and risk of acute myocardial infarction: a nationwide study.
Osteoporotic fractures are associated with increased mortality risk. However, little data are available on the risk of acute myocardial infarction (AMI) after hip fracture. Therefore, we investigated whether hip fracture increased the risk of AMI in a large, nationwide cohort study. We obtained data from 8758 patients diagnosed with hip fracture from 2000 to 2009 and from 4 matched controls for each patient from the Longitudinal Health Insurance Database (LHID 2000), Taiwan. Controls were matched for age, sex, comorbid disorders, and enrollment date. All subjects were followed up from the date of enrollment until AMI, death, or the end of data collection (2009). Cox's regression model adjusted for age, sex, comorbid disorders, and medication was used to assess independent factors determining the risk of development of AMI. As expected, despite the matching, the hip fracture patients had more risk factors for AMI at baseline. A total of 8758 subjects with hip fractures and 35,032 controls were identified. Among these patients, 1183 (257 hip fracture patients and 926 controls) developed AMI during the median 3.2-year (interquartile range 1.4 to 5.8 years) follow-up period. Patients with hip fractures had a higher incidence of AMI occurrence when compared with controls (8.7/1000 person-years versus 6.82/1000 person-years). Multivariate analysis adjusted for baseline covariates indicated that hip fracture was associated with a greater risk for AMI development (hazard ratio [HR] = 1.29; 95% confidence interval [CI] 1.12-1.48; p < 0.001). We conclude that hip fracture is independently associated with a higher risk of subsequent AMI.


Evaluation of early skin cancer detection in Germany with cancer registry data - challenges, solutions and current trends.
The evidence for the benefit of the skin cancer screening introduced in Germany in 2008 is weak. We investigate to what extent data from the German epidemiological cancer registries are suitable to contribute to the evaluation of skin cancer screening and report these evaluation results. Skin cancer-related cancer registry data from 1999-2019 were described in terms of completeness and comprehensiveness. Regional pools with data of different validity were defined, missing data were multiply imputed where appropriate, and temporal trends were analyzed. In addition, data from the cause of death statistics were used. Reliable estimates of completeness are only available for malignant melanoma (ICD-10: C43). Based on a regional data pool covering approximately 21% of the German population, melanoma-related incidence can be validly described since 2005. Sufficient information for multiple imputation is available for T-stage and localization. The trend analyses show incidence changes that can be expected in the short term in the temporal context of the introduction of early detection, which changes into a long-lasting high incidence. The rate of advanced stages does not decrease significantly. From 2014 onwards, the melanoma mortality rate, which had been rising until then, decreases. Adequately selected and processed cancer registry data are suitable for population-based evaluation of skin cancer screening. An explanation of the persistently high incidence level is not possible based on the cancer registry data. Overdiagnosis or an increase in the background incidence can be considered. The benefit of skin cancer screening remains open.


Controlling Legionella in hospital water systems: experience with the superheat-and-flush method and copper-silver ionization.
To evaluate the effect of copper-silver ionization on Legionella colonization and nosocomial legionnaires' disease and to compare the efficacy of metal ions versus the superheat-and-flush method of disinfection. Prospective determination over a 36-month period of copper and silver ion concentrations in the recirculating hot-water system, Legionella colonization of the hospital water distribution system, and cases of nosocomial legionnaires' disease. Retrospective comparison of results with the previous 13 years, during which the superheat-and-flush method was used. The Pittsburgh Veterans' Affairs Health Care System (University Drive Division) acute-care hospital. Three copper-silver ionization systems were installed on the hot-water distribution system in November 1994. The average number of cases of legionnaires' disease per year and the percentage of distal sites positive for Legionella pneumophila for the superheat-and-flush method versus the copper-silver ionization method was six cases with 15% positivity versus two cases with 4% positivity, respectively. The reduction in Legionella colonization after copper-silver ionization was significant (P<.05) compared to the superheat and flush. Mean copper and silver ion concentrations (mg/L) were 0.29 and 0.054 from hot-water tanks, and 0.17 and 0.04 from distal outlets, respectively. We conclude that a properly maintained and monitored copper-silver ionization system was more effective than the superheat-and-flush method for reducing the recovery of Legionella from the hospital water distribution system.


Bone Morphogenetic Protein 2 Alters Osteogenesis and Anti-Inflammatory Profiles of Mesenchymal Stem Cells Induced by Microtextured Titanium In Vitro<sup/>.
Microtextured titanium (Ti) induces osteoblast differentiation of mesenchymal stem cells (MSCs) in the absence of exogenous osteogenic factors; and high-energy surface modifications speed healing of microrough Ti implants. Bone morphogenetic protein 2 (BMP2) is used clinically to improve peri-implant bone formation and osseointegration but can cause inflammation and bone-related complications. In this study, we determined whether BMP2 alters human MSC differentiation, apoptosis, and inflammatory factor production when grown on Ti implants with different surface properties. Human MSCs were cultured on Ti substrates (smooth [PT], sandblasted acid-etched [SLA], hydrophilic-SLA [modSLA]), or tissue culture polystyrene (TCPS). After 7 days, inflammatory mRNAs were measured by polymerase chain reaction array. In addition, 7-day cultures were treated with exogenous BMP2 and osteogenic differentiation and production of local factors, proinflammatory interleukins, and anti-inflammatory interleukins assessed. Finally, osteogenic markers and interleukins were measured in MSCs cultured for 48 h on BMP2 dip-coated SLA and modSLA surfaces. Expression of interleukins, chemokines, cytokines, and growth factors was affected by surface properties, particularly on modSLA. MSCs on Ti produced fewer resorptive and more osteogenic/anti-inflammatory factors than cells on TCPS. Addition of 100 ng/mL BMP2 not only increased differentiation but also increased proinflammatory and decreased anti-inflammatory/antiresorptive factors. Two hundred nanograms per milliliter BMP2 abolished osteogenesis and dramatically increased pro-osteoclastogenic factors. MSCs cultured on BMP2-dip-coated disks produced similar proinflammatory profiles with inhibited osteogenic differentiation and had increased apoptotic markers at the highest doses. MSCs underwent osteogenesis and regulated inflammatory cytokines on microtextured Ti. Exogenous BMP2 inhibited MSC differentiation and stimulated a dose-dependent proinflammatory and apoptotic response. Use of BMP2 with microtextured metal implants may increase inflammation and possibly delay bone formation dependent on dose, suggesting that application of BMP2 clinically during implant insertion may need to be reevaluated.


Scaling up health interventions in resource-poor countries: what role does research in stated-preference framework play?
Despite improved supply of health care services in low-income countries in the recent past, their uptake continues to be lower than anticipated. This has made it difficult to scale-up those interventions which are not only cost-effective from supply perspectives but that might have substantial impacts on improving the health status of these countries. Understanding demand-side barriers is therefore critically important. With the help of a case study from Nepal, this commentary argues that more research on demand-side barriers needs to be carried out and that the stated-preference (SP) approach to such research might be helpful. Since SP techniques place service users' preferences at the centre of the analysis, and because preferences reflect individual or social welfare, SP techniques are likely to be helpful in devising policies to increase social welfare (e.g. improved service coverage). Moreover, the SP data are collected in a controlled environment which allows straightforward identification of effects (e.g. that of process attributes of care) and large quantities of relevant data can be collected at moderate cost. In addition to providing insights into current preferences, SP data also provide insights into how preferences are likely to respond to a proposed change in resource allocation (e.g. changing service delivery strategy). Finally, the SP-based techniques have been used widely in resource-rich countries and their experience can be valuable in conducting scaling-up research in low-income countries.


Application of an Innovative Data Mining Approach Towards Safe Polypharmacy Practice in Older Adults.
Polypharmacy is common and is associated with higher risk of adverse drug event (ADE) among older adults. Knowledge on the ADE risk level of exposure to different drug combinations is critical for safe polypharmacy practice, while approaches for this type of knowledge discovery are limited. The objective of this study was to apply an innovative data mining approach to discover high-risk and alternative low-risk high-order drug combinations (e.g., three- and four-drug combinations). A cohort of older adults (≥ 65 years) who visited an emergency department (ED) were identified from Medicare fee-for-service and MarketScan Medicare supplemental data. We used International Classification of Diseases (ICD) codes to identify ADE cases potentially induced by anticoagulants, antidiabetic drugs, and opioids from ED visit records. We assessed drug exposure data during a 30-day window prior to the ED visit dates. We investigated relationships between exposure of drug combinations and ADEs under the case-control setting. We applied the mixture drug-count response model to identify high-order drug combinations associated with an increased risk of ADE. We conducted therapeutic class-based mining to reveal low-risk alternative drug combinations for high-order drug combinations associated with an increased risk of ADE. We investigated frequent high-order drug combinations from 8.4 million ED visit records (5.1 million from Medicare data and 3.3 million from MarketScan data). We identified 5213 high-order drug combinations associated with an increased risk of ADE by controlling the false discovery rate at 0.01. We identified 1904 high-order, high-risk drug combinations had potential low-risk alternative drug combinations, where each high-order, high-risk drug combination and its corresponding low-risk alternative drug combination(s) have similar therapeutic classes. We demonstrated the application of a data mining technique to discover high-order drug combinations associated with an increased risk of ADE. We identified high-risk, high-order drug combinations often have low-risk alternative drug combinations in similar therapeutic classes.


The effect of complete decongestive therapy on the quality of life of patients with peripheral lymphedema.
Lymphedema is a chronic disorder which can adversely affect quality of life (QOL). The purpose of this study was 1) to evaluate whether QOL was improved in patients with lymphedema following Complete Decongestive Therapy (CDT), and 2) whether limb volume change as a result of treatment correlated with change in QOL. Thirty-six patients with peripheral lymphedema from varying causes were enrolled in the study. The QOL of each participant, with regard to physical, functional, and psychosocial concerns, was measured by pre- and post-treatment questionnaires. Percent edema volume reduction was calculated for each patient with only one affected limb. QOL pre- and post-treatment scores were assessed by multivariate repeated measures analysis. QOL scores differed significantly (p<0.05) between pre- and posttreatment in all areas of inquiry. Patients with lower extremity lymphedema had significantly greater mean improvement in QOL scores compared with patients with upper extremity lymphedema (p=0.02). There was no correlation between percent edema volume reduction and post-treatment QOL improvement. This study suggests that significant improvements are made in the QOL of patients exhibiting peripheral lymphedema following CDT, which is not necessarily correlated with limb volume reduction.


Wavelet-Based Demodulation of Multimode Etched Fiber Bragg Grating Refractive Index Sensor.
Etched fiber Bragg grating (EFBG)-based sensors are used as evanescent field sensors for refractive index detection. When the fiber thickness is thin and the refractive index sensitivity increases, the number of propagating modes increases, resulting in a spectral enlargement that complicates the interrogation of the sensor. In this work, we present a method to analyze the spectrum of a multimode etched fiber Bragg grating (MMEFBG) in the wavelet domain, which analyzes the amount of spectral density independently from the peak reflectivity value. The proposed interrogation method permits defining the integral of the spectral density as a novel and unconventional estimator. With respect to the conventional estimators based on wavelength shift, this estimator can better exploit the larger amount of information given by the spectral enlargement typical of multimode behavior. Results were obtained by etching an MMEFBG in hydrofluoric acid and using water/sucrose mixtures to evaluate the refractive index sensitivity, validating the interrogation method.