Contrasting distribution patterns between aquatic and terrestrial Phytophthora species along a climatic gradient are linked to functional traits.
Diversity of microbial organisms is linked to global climatic gradients. The genus Phytophthora includes both aquatic and terrestrial plant pathogenic species that display a large variation of functional traits. The extent to which the physical environment (water or soil) modulates the interaction of microorganisms with climate is unknown. Here, we explored the main environmental drivers of diversity and functional trait composition of Phytophthora communities. Communities were obtained by a novel metabarcoding setup based on PacBio sequencing of river filtrates in 96 river sites along a geographical gradient. Species were classified as terrestrial or aquatic based on their phylogenetic clade. Overall, terrestrial and aquatic species showed contrasting patterns of diversity. For terrestrial species, precipitation was a stronger driver than temperature, and diversity and functional diversity decreased with decreasing temperature and precipitation. In cold and dry areas, the dominant species formed resistant structures and had a low optimum temperature. By contrast, for aquatic species, temperature and water chemistry were the strongest drivers, and diversity increased with decreasing temperature and precipitation. Within the same area, environmental filtering affected terrestrial species more strongly than aquatic species (20% versus 3% of the studied communities, respectively). Our results highlight the importance of functional traits and the physical environment in which microorganisms develop their life cycle when predicting their distribution under changing climatic conditions. Temperature and rainfall may be buffered differently by water and soil, and thus pose contrasting constrains to microbial assemblies.


Separating chemical shift and quadrupolar anisotropies via multiple-quantum NMR spectroscopy.
Chemical shift anisotropy (CSA) has been an invaluable probe of structure and dynamics for a variety of systems in NMR spectroscopy. Unfortunately, the presence of strong quadrupolar couplings has severely limited the ability to measure CSA in nuclei with spins I > 1/2. Here we show that these two interactions can be refocused at different times in a 2D multiple-quantum NMR experiment on polycrystalline samples. Combining this experiment with appropriate affine transformations allows these interactions to be cleanly separated into orthogonal dimensions. The 1D projection onto each axis can be fit to extract the respective principal tensor components. These components can then be used to fit the 2D spectrum for the relative orientation between the CSA and quadrupolar-coupling tensors. The necessary affine transformation parameters are given for all possible I values. Illustrative examples of spectra and analyses are given for 63Cu in K3[Cu(CN)4], 59Co in K3[Co(CN)6], and 87Rb in RbCrO4.


Performance on the test of memory malingering (TOMM) among a large clinic-referred pediatric sample.
Growing concerns with suboptimal effort in pediatric populations have led clinicians to investigate the utility of symptom validity tests (SVT) among children and adolescents. Performance on the Test of Memory Malingering (TOMM) was analyzed among a clinical sample of individuals ranging in age from 5 through 16 years. The 101 patients were referred for a variety of learning, developmental, psychiatric, and neurological concerns. All children were administered the TOMM as part of a clinical neuropsychological evaluation. Within the sample, 4 patients did not meet the adult cutoff criteria for passing the TOMM. Three of the 4 patients also demonstrated suboptimal effort on another SVT. Results revealed statistically significant correlations between TOMM performance and age, intelligence, and memory. Despite these correlations, 97 out of the 101 performed at or above the adult cutoff score. The findings suggest that children perform similarly to adults on the TOMM and that the TOMM is appropriate for use with pediatric clinical populations as young as 5 years.


Functional surfaces on the p35/ARPC2 subunit of Arp2/3 complex required for cell growth, actin nucleation, and endocytosis.
The Arp2/3 complex is comprised of seven evolutionarily conserved subunits and upon activation by WASp or another nucleation promoting factor nucleates the formation of actin filaments. These events are critical for driving a wide range of cellular processes, including motility, endocytosis, and intracellular trafficking. However, an in depth understanding of the Arp2/3 complex activation and nucleation mechanism is still lacking. Here, we used a mutagenesis approach in Saccharomyces cerevisiae to dissect the structural and functional roles of the p35/ARPC2 subunit. Using integrated alleles that target conserved and solvent-exposed residues, we identified surfaces on p35/ARPC2 required for cell growth, actin organization, and endocytosis. In parallel, we purified the mutant Arp2/3 complexes and compared their actin assembly activities both in the presence and in the absence of WASp. The majority of alleles with defects mapped to one face of p35/ARPC2, where there was a close correlation between loss of actin nucleation and endocytosis. A second site required for nucleation and endocytosis was identified near the contact surface between p35/ARPC2 and p19/ARPC4. A third site was identified at a more distal conserved surface, which was critical for endocytosis but not nucleation. These findings pinpoint the key surfaces on p35/ARPC2 required for Arp2/3 complex-mediated actin assembly and cellular function and provide a higher resolution view of Arp2/3 structure and mechanism.


Selenium controls transcription of paralogous formate dehydrogenase genes in the termite gut acetogen, Treponema primitia.
The termite gut spirochete, Treponema primitia, is a CO(2)-reductive acetogen that is phylogenetically distinct from other distantly related and more extensively studied acetogens such as Moorella thermoacetica. Research on T. primitia has revealed details about the role of spirochetes in CO(2)-reductive acetogenesis, a process important to the mutualism occurring between termites and their gut microbial communities. Here, a locus of the T. primitia genome containing Wood-Ljungdahl pathway genes for CO(2)-reductive acetogenesis was sequenced. This locus contained methyl-branch genes of the pathway (i.e. for the reduction of CO(2) to the level of methyl-tetrahydrofolate) including paralogous genes for cysteine and selenocysteine (Sec) variants of formate dehydrogenase (FDH) and genes for Sec incorporation. The FDH variants affiliated phylogenetically with hydrogenase-linked FDH enzymes, suggesting that T. primitia FDH enzymes utilize electrons derived directly from molecular H(2). Sub-nanomolar concentrations of selenium decreased transcript levels of the cysteine variant FDH gene. Selenium concentration did not markedly influence the level of mRNA upstream of the Sec-codon in the Sec variant FDH; however, the level of transcript extending downstream of the Sec-codon increased incrementally with increasing selenium concentrations. The features and regulation of these FDH genes are an indication that T. primitia may experience dynamic selenium availability in its H(2)-rich gut environment.


Associations between dietary intake and Ki-ras mutations in colon tumors: a population-based study.
Ki-ras mutations are thought to be early events in the carcinogenic process leading to colon tumors. Dietary factors associated with colon cancer may be associated with these mutations. Data from a population-based, multicenter, case-control study of colon cancer were used to determine whether dietary factors are associated with Ki-ras mutations. Ki-ras mutations were detected by direct sequencing of codons 12 and 13 of the Ki-ras gene on exon 1 from DNA obtained from archival tissue. Ki-ras data were available for 1428 cases with valid interview data; data from 2410 controls were available for comparison with cases positive and negative for Ki-ras mutations. Mutations in the Ki-ras gene were detected in 32% of tumors. Of these mutations, 32.8% were G-->A transitions in the second base of codon 12 (2G-->A). Other than cruciferous vegetables, there were no nutrients or foods associated specifically with Ki-ras mutations [odds ratio (OR) for high intake relative to low intake, 0.7; 95% confidence interval (CI), 0.5-1.0]. However, evaluation of specific types of Ki-ras mutations revealed that for each of the most common types of mutation, dietary associations existed. Dietary factors involved in DNA methylation pathways were associated with 2G-->A mutations. Comparison of individuals with and without Ki-ras mutations revealed that individuals with low levels of dietary folate (OR, 0.7; 95% CI, 0.4-1.3), vitamin B6 (OR, 0.5; 95% CI, 0.3-1.0), vitamin B12 (OR, 0.6; 95% CI, 0.3-1.1), and high levels of alcohol (OR, 0.7; 95% CI, 0.4-1.1) were less likely to have a 2G-->A mutation. Individuals with high levels of dietary carbohydrate (OR, 2.0; 95% CI, 0.9-4.4) and a high glycemic index (OR, 1.9; 95% CI, 0.8-4.6) were more likely to have a G-->A transition mutation in the second base of codon 13 (5G-->A). Individuals with high levels of dietary fat (OR, 1.6; 95% CI, 0.8-3.2), saturated fat (OR, 1.7; 95% CI, 0.8-3.5), and monounsaturated fat (OR, 1.9; 95% CI, 1.0-3.7) were more likely to harbor a 2G-->T mutation. Low levels of cruciferous vegetable intake and high levels of processed meat intake also were associated with fewer 5G-->A, as reflected by the ORs (OR, 0.4; 95% CI, 0.2-1.0 and OR, 0.4; 95% CI 0.2-0.8, respectively). These data suggest that diet may be involved in disease pathways represented by specific Ki-ras mutations. However, given the limited information currently available on associations between specific genetic mutations in colon tumors and diet, these findings also should be viewed as hypothesis generating.


Sweet preferences and analgesia during childhood: effects of family history of alcoholism and depression.
To determine whether depression and family history of alcoholism are associated with heightened sweet preferences in children, before they have experienced alcohol or tobacco and at a time during the life-span when sweets are particularly salient. Design Between- and within-subject experimental study. Children, 5-12 years old (n = 300), formed four groups based on family history of alcohol dependence up to second-degree relatives [positive (FHP) versus negative (FHN)] and depressive symptoms as determined by the Pictorial Depression Scale [depressed (PDEP) versus non-depressed (NDEP)]. Children were tested individually to measure sucrose preferences, sweet food liking and, for a subset of the children, the analgesic properties of sucrose versus water during the cold pressor test. The co-occurrence of having a family history of alcoholism and self-reports of depressive symptomatology was associated significantly with a preference for a more concentrated sucrose solution, while depressive symptomatology alone was associated with greater liking for sweet-tasting foods and candies and increased pain sensitivity. Depression antagonized the analgesic properties of sucrose. While children as a group innately like sweets and feel better after eating them, the present study reveals significant contributions of family history of alcoholism and depression to this effect. Whether the heightened sweet preference and the use of sweets to alleviate depression are markers for developing alcohol-related problems or responses that are protective are important areas for future research.


Occupational activity and the risk of osteoarthritis.
Osteoarthritis (OA) is now recognized as a major public health problem. The risk of OA depends upon factors that increase generalized susceptibility to the disorder, as well as biomechanical factors that modify risk at specific joint sites. Occupational physical activity is one of the important influences in this latter category. Epidemiological evidence has begun to mount that occupational physical activity is a determinant of the risk of knee and hip OA. Occupations that involve regular knee bending and heavy lifting confer a greater likelihood of developing knee OA, while there appears to be a particular propensity for hip OA among farmers. Further research into these relationships will have two important consequences: (1) The issue whether industrial recompense is justified for workers in these industries who develop OA will be clarified. (2) A clearer understanding of the pathophysiology of these relationships will lead to more effective preventive strategies.


Extreme compression and modeling of bidirectional texture function.
The recent advanced representation for realistic real-world materials in virtual reality applications is the Bidirectional Texture Function (BTF) which describes rough texture appearance for varying illumination and viewing conditions. Such a function can be represented by thousands of measurements (images) per material sample. The resulting BTF size excludes its direct rendering in graphical applications and some compression of these huge BTF data spaces is obviously inevitable. In this paper we present a novel, fast probabilistic model-based algorithm for realistic BTF modeling allowing an extreme compression with the possibility of a fast hardware implementation. Its ultimate aim is to create a visual impression of the same material without a pixel-wise correspondence to the original measurements. The analytical step of the algorithm starts with a BTF space segmentation and a range map estimation by photometric stereo of the BTF surface, followed by the spectral and spatial factorization of selected sub-space color texture images. Single mono-spectral band-limited factors are independently modeled by their dedicated spatial probabilistic model. During rendering, the sub-space images of arbitrary size are synthesized and both color (possibly multi-spectral) and range information is combined in a bump-mapping filter according to the view and illumination directions. The presented model offers a huge BTF compression ratio unattainable by any alternative sampling-based BTF synthesis method. Simultaneously this model can be used to reconstruct missing parts of the BTF measurement space.


Food fortification as a complementary strategy for the elimination of micronutrient deficiencies: case studies of large scale food fortification in two Indian States.
The burden of micronutrient malnutrition is very high in India. Food fortification is one of the most cost-effective and sustainable strategies to deliver micronutrients to large population groups. Global Alliance for Improved Nutrition (GAIN) is supporting large-scale, voluntary, staple food fortification in Rajasthan and Madhya Pradesh because of the high burden of malnutrition, availability of industries capable of and willing to introduce fortified staples, consumption patterns of target foods and a conducive and enabling environment. High extraction wheat flour from roller flour mills, edible soybean oil and milk from dairy cooperatives were chosen as the vehicles for fortification. Micronutrients and levels of fortification were selected based on vehicle characteristics and consumption levels. Industry recruitment was done after a careful assessment of capability and willingness. Production units were equipped with necessary equipment for fortification. Staffs were trained in fortification and quality control. Social marketing and communication activities were carried out as per the strategy developed. A state food fortification alliance was formed in Madhya Pradesh with all relevant stakeholders. Over 260,000 MT of edible oil, 300,000 MT of wheat flour and 500,000 MT of milk are being fortified annually and marketed. Rajasthan is also distributing 840,000 MT of fortified wheat flour annually through its Public Distribution System and 1.1 million fortified Mid-day meals daily through the centralised kitchens. Concurrent monitoring in Rajasthan and Madhya has demonstrated high compliance with all quality standards in fortified foods.


The incidence and risk factors of acute kidney injury after hepatobiliary surgery: a prospective observational study.
Although intraperitoneal surgery is a major operation associated with postoperative acute kidney injury (AKI), the incidence, risk factors, and long-term renal outcome are not well known. We aimed to determine the risk factors and 6 months renal outcome in patients with clinical or subclinical AKI after hepatobiliary surgery. We also assessed the validity of urine neutrophil gelatinase-associated lipocalin (NGAL) in the early detection of AKI or prediction of renal outcome. This prospective observational study enrolled patients with normal renal function who underwent hepatobiliary surgeries. Urine and serum samples were collected for NGAL measurement. Among 131 patients, 10 (7.6%) developed postoperative AKI. Urine NGAL at 12 h postsurgery was the most predictive parameter for the diagnosis of AKI (cutoff, 92.85 ng/mL). With the cutoff value, subclinical AKI was diagnosed in 42 (32.1%) patients. Patients with clinical AKI and those with subclinical AKI were assigned to the AKI group. The AKI group had significantly higher model for end-stage liver disease and sodium (MELD-Na) score, lower albumin level, and longer hospital stay after surgery than the non-AKI group. Older age and higher MELD-Na score were independent risk factors for the development of postoperative AKI. At 6 months postsurgery, the estimated glomerular filtration rate (eGFR) in the AKI group was significantly lower than that in the non-AKI group, although the baseline eGFR was not different. In multiple linear regression analysis, the maximum urine NGAL level during 24 h postsurgery, intraoperative fluid balance, and having liver transplantation were significantly associated with a poor 6 months renal outcome. Urine NGAL was useful in the early diagnosis of postoperative AKI as well as in predicting the 6 months renal outcome after hepatobiliary surgery. A considerable proportion of patients developed subclinical AKI, and these patients showed worse renal outcome compared with the non-AKI group.


Bioanalytical utility of sonovoltammetry.
Dopamine dissolved within egg homogenate was used as a model system to study the effects of electrode contamination and its subsequent reactivation through ultrasonically mediated in situ cleaning effects. The merits in conducting electroanalytical investigations under the influence of the ultrasonic field were also appraised. Maintaining the ultrasound field during oxidative measurements was found to yield hydrodynamic profiles that were linear over the concentration range 2-20 microM dopamine. The resulting sonolinear sweep voltammograms were compared with conventional rotating disk measurements, with the former found to provide significantly increased limiting currents that were attenuable through the manipulation of the field intensity. The problem of retaining selectivity in the presence of high concentrations of ascorbate was also assessed with the addition of cupric ion prior to commencing the measurements found to efficiently negate an otherwise substantive interference.


Deep genetic divergence between disjunct Refugia in the Arctic-Alpine King's Crown, Rhodiola integrifolia (Crassulaceae).
Despite the strength of climatic variability at high latitudes and upper elevations, we still do not fully understand how plants in North America that are distributed between Arctic and alpine areas responded to the environmental changes of the Quaternary. To address this question, we set out to resolve the evolutionary history of the King's Crown, Rhodiola integrifolia using multi-locus population genetic and phylogenetic analyses in combination with ecological niche modeling. Our population genetic analyses of multiple anonymous nuclear loci revealed two major clades within R. integrifolia that diverged from each other ~ 700 kya: one occurring in Beringia to the north (including members of subspecies leedyi and part of subspecies integrifolia), and the other restricted to the Southern Rocky Mountain refugium in the south (including individuals of subspecies neomexicana and part of subspecies integrifolia). Ecological niche models corroborate our hypothesized locations of refugial areas inferred from our phylogeographic analyses and revealed some environmental differences between the regions inhabited by its two subclades. Our study underscores the role of geographic isolation in promoting genetic divergence and the evolution of endemic subspecies in R. integrifolia. Furthermore, our phylogenetic analyses of the plastid spacer region trnL-F demonstrate that among the native North American species, R. integrifolia and R. rhodantha are more closely related to one another than either is to R. rosea. An understanding of these historic processes lies at the heart of making informed management decisions regarding this and other Arctic-alpine species of concern in this increasingly threatened biome.


Understanding deep-water striation patterns and predicting the waveguide invariant as a distribution depending on range and depth.
The Waveguide Invariant (WI) theory has been introduced to quantify the orientation of the intensity interference patterns in a range-frequency domain. When the sound speed is constant over the water column, the WI is a scalar with the canonical value of 1. But, when considering shallow waters with a stratified sound speed profile, the WI ceases to be constant and is more appropriately described by a distribution, which is mainly sensitive to source/receiver depths. Such configurations have been widely investigated, with practical applications including passive source localization. However, in deep waters, the interference pattern is much more complex and variable. In fact the observed WI varies with source/receiver depth but it also varies very quickly with source-array range. In this paper, the authors investigate two phenomena responsible for this variability, namely the dominance of the acoustic field by groups of modes and the frequency dependence of the eigenmodes. Using a ray-mode approach, these two features are integrated in a WI distribution derivation. Their importance in deep-water is validated by testing the calculated WI distribution against a reference distribution directly measured on synthetic data. The proposed WI derivation provides a thorough way to predict and understand the striation patterns in deep-water context.


Rapid Detection of Heterogeneous Vancomycin-Intermediate Staphylococcus aureus Based on Matrix-Assisted Laser Desorption Ionization Time-of-Flight: Using a Machine Learning Approach and Unbiased Validation.
Heterogeneous vancomycin-intermediate Staphylococcus aureus (hVISA) is an emerging superbug with implicit drug resistance to vancomycin. Detecting hVISA can guide the correct administration of antibiotics. However, hVISA cannot be detected in most clinical microbiology laboratories because the required diagnostic tools are either expensive, time consuming, or labor intensive. By contrast, matrix-assisted laser desorption ionization time-of-flight (MALDI-TOF) is a cost-effective and rapid tool that has potential for providing antibiotics resistance information. To analyze complex MALDI-TOF mass spectra, machine learning (ML) algorithms can be used to generate robust hVISA detection models. In this study, MALDI-TOF mass spectra were obtained from 35 hVISA/vancomycin-intermediate S. aureus (VISA) and 90 vancomycin-susceptible S. aureus isolates. The vancomycin susceptibility of the isolates was determined using an Etest and modified population analysis profile-area under the curve. ML algorithms, namely a decision tree, k-nearest neighbors, random forest, and a support vector machine (SVM), were trained and validated using nested cross-validation to provide unbiased validation results. The area under the curve of the models ranged from 0.67 to 0.79, and the SVM-derived model outperformed those of the other algorithms. The peaks at m/z 1132, 2895, 3176, and 6591 were noted as informative peaks for detecting hVISA/VISA. We demonstrated that hVISA/VISA could be detected by analyzing MALDI-TOF mass spectra using ML. Moreover, the results are particularly robust due to a strict validation method. The ML models in this study can provide rapid and accurate reports regarding hVISA/VISA and thus guide the correct administration of antibiotics in treatment of S. aureus infection.


AKT-mediated stabilization of histone methyltransferase WHSC1 promotes prostate cancer metastasis.
Loss of phosphatase and tensin homolog (PTEN) and activation of the PI3K/AKT signaling pathway are hallmarks of prostate cancer (PCa). However, these alterations alone are insufficient for cells to acquire metastatic traits. Here, we have shown that the histone dimethyl transferase WHSC1 critically drives indolent PTEN-null tumors to become metastatic PCa. In a PTEN-null murine PCa model, WHSC1 overexpression in prostate epithelium cooperated with Pten deletion to produce a metastasis-prone tumor. Conversely, genetic ablation of Whsc1 prevented tumor progression in PTEN-null mice. Molecular characterization revealed that increased AKT activity due to PTEN loss directly phosphorylates WHSC1 at S172, preventing WHSC1 degradation by CRL4Cdt2 E3 ligase. Increased WHSC1 expression transcriptionally upregulates expression of RICTOR, a pivotal component of mTOR complex 2 (mTORC2), to further enhance AKT activity. Therefore, the AKT/WHSC1/mTORC2 signaling cascade represents a vicious feedback loop that elicits unrestrained AKT signaling. Furthermore, we determined that WHSC1 positively regulates Rac1 transcription to increase tumor cell motility. The biological importance of a WHSC1-mediated signaling cascade is substantiated by patient sample analysis in which WHSC1 signaling is tightly correlated with disease progression and recurrence. Taken together, our findings highlight a pivotal link between an epigenetic regulator, WHSC1, and key intracellular signaling molecules, AKT, RICTOR, and Rac1, to drive PCa metastasis.


The role of prostaglandins E2 and F2 alpha in ultraviolet radiation-induced cortical cataracts in vivo.
Previous work has shown that exposure of lens epithelial cells or rabbit eyes in vivo to ultraviolet B (UVB) radiation enhanced prostaglandin (PG)E2 synthesis. Such enhanced PGE2 synthesis was related to the increased DNA synthesis that followed UVB exposure. The current study examined the relationship between enhanced prostaglandin synthesis and UVB-induced cataract formation. Seventy albino (New Zealand white) rabbit eyes were exposed to UVB radiation in vivo. Fluence of radiation at the cornea was 2.8 J/cm2, 5.6 J/cm2, or 11.2 J/cm2. Eyes were examined 24 hours after UVB exposure and for as long as 10 days by slit lamp biomicroscopy. Mass spectrometry was used to measure PGE2, PGF2 alpha, and 6-keto-PGF1 alpha content of the lens and iris-ciliary body using authentic standards. To determine the effect of inhibition of prostaglandin synthesis on UVB-induced cataract formation, animals were given indomethacin intraperitoneally. Other pharmacologic agents, such as PGE2, PGF2 alpha, and misoprostol, were applied topically to the eye. The effect of UVB on K+ pump was determined by incubating isolated lenses with [86Rb+]. Twenty-four hours after UVB exposure, PGE2 and PGF2 alpha concentrations in aqueous humor were increased by 100- and 30-fold, respectively. Lens PGE2 and PGF2 alpha increased by 6- and 4-fold, respectively, after UVB radiation exposure. Pretreatment of animals with indomethacin prevented the rise in lens and aqueous humor PGE2 and PGF2 alpha levels. Furthermore, indomethacin was partially protective against UVB cataract formation and lowered cataract severity from stage 3 to stage 1, but it did not prevent UVB-induced lens changes completely. Topical application of PGE2 before UVB exposure completely prevented cataract formation in the UVB-exposed eye. In contrast, topical administration of PGF2 alpha increased cataract severity. UVB-induced cataract formation preceded changes in [86Rb]+ uptake in lenses subsequently incubated in K(+)-free Tyrode's. Enhanced synthesis of cyclooxygenase products of arachidonic acid metabolism in the lens is associated with UVB-induced cataract formation in albino rabbit eyes, and inhibition of cyclooxygenase by indomethacin decreased the severity of cataracts. PGE2, the principal arachidonic acid metabolite, appears to have a protective role because pretreatment of the eye with topical PGE2 completely prevented UVB-induced cataract formation, whereas PGF2 alpha increased the severity of the cataract. The evidence presented for a role of PGF2 alpha in the development of cataract suggests that caution be exercised in the use of PGF2 alpha derivatives in the therapy of glaucoma.


An exploratory clinical trial of bortezomib in patients with lower risk myelodysplastic syndromes.
Myelodysplastic syndromes (MDSs) are characterized by ineffective hematopoiesis and an increased risk of transformation. Few effective therapies are available for lower risk MDS patients, especially after the failure of hypomethylating agents. MDS progenitor cells are dependent on the nuclear factor-κB (NF-κB) for survival, which makes it an attractive therapeutic target. As a proteosomal inhibitor, bortezomib is thought to have inhibitory activity against NF-κB. We designed a proof-of-principle study of subcutaneous (SC) bortezomib in lower risk MDS patients with evidence of NF-κB activation in their bone marrow. Fifteen patients were treated, their median age was 71 (range 56-87), 33% were low and 67% int-1 by IPSS, median number of prior therapies was 2, all patients were transfusion dependent. Baseline median pp65 percentage was 31% and 11 patients had evidence of ring sideroblasts (RS). SC bortezomib was safe, well tolerated with no excess toxicity. Three patients out of the 15 (20%) had evidence of response with hematologic improvement (HI-E). Bortezomib caused a decrease in pp65 levels in 7 out of 13 evaluable patients (54%, P = .025). Of interest, unexpectedly, we observed a significant decrease in RS in 7 out of 10 (70%) evaluable patients during treatment. In conclusion, this study suggests that NF-κB activation, measured by pp65 levels, may be a useful biomarker in MDS. Bortezomib is safe in this patient population but has modest clinical activity. The role of the proteasome in the genesis of RS needs further study.


Algorithmic Tools for Mining High-Dimensional Cytometry Data.
The advent of mass cytometry has led to an unprecedented increase in the number of analytes measured in individual cells, thereby increasing the complexity and information content of cytometric data. Although this technology is ideally suited to the detailed examination of the immune system, the applicability of the different methods for analyzing such complex data is less clear. Conventional data analysis by manual gating of cells in biaxial dot plots is often subjective, time consuming, and neglectful of much of the information contained in a highly dimensional cytometric dataset. Algorithmic data mining has the promise to eliminate these concerns, and several such tools have been applied recently to mass cytometry data. We review computational data mining tools that have been used to analyze mass cytometry data, outline their differences, and comment on their strengths and limitations. This review will help immunologists to identify suitable algorithmic tools for their particular projects.


Extracellular calcium regulates expression of the gene for atrial natriuretic factor.
Primary cultures of neonatal rat cardiocytes were exposed for 24 hours to culture media containing 0-2.0 mM extracellular calcium. Both atrial natriuretic factor (ANF) messenger RNA (mRNA) and ANF secretion were increased approximately threefold in the presence of 2.0 mM CaCl2 (vs. Ca2(+)-free medium). When cardiocytes were treated with the calcium channel blockers diltiazem, nifedipine, or verapamil, both ANF synthesis and secretion fell to 25-40% of control values. The choice of transcription start site on the ANF gene was not altered by the calcium channel blockers. When exogenous calcium was added to cardiocytes treated with verapamil, secretion of ANF was partially restored to control levels. High-performance liquid chromatographic analysis of medium from cardiocytes exposed to varying extracellular calcium concentrations or treated with calcium channel blockers for 24 hours revealed that the majority of secreted immunoreactivity (60-70%) migrated with pro-ANF (17 kDa) and that none of the various experimental manipulations significantly changed the ratio of pro-ANF to ANF in the media. These results were confirmed by immunoprecipitation analysis of the culture medium from the individual treatment groups. Treatment of cardiocytes for 24 hours with either the calcium ionophore A23187 or the phorbol ester 12-O-tetradecanoylphorbol 13-acetate increased ANF secretion. The combined use of these agents resulted in stimulation of both ANF secretion and ANF mRNA accumulation.


Chronic Otitis Media with Granulation Is a Poor Prognostic Factor for Hearing Improvement and Development of Intracranial Complications.
Different types of chronic otitis media are distinguished based on the observed lesions in the middle ear mucous. Hearing improvement is a measurable effect of the surgical treatment of patients with chronic otitis media. Chronic cholesteatoma otitis media and chronic otitis media with inflammatory granulation have a tendency to damage the bone tissue, leading to the development of intratemporal and intracranial complications. A prospective analysis of patients who underwent surgery for the first time due to chronic otitis media from 2009 to 2012 was performed. Patients were divided into groups according to the abnormalities of the middle ear mucous observed during otosurgery. Special attention was given to patients diagnosed with chronic otitis media with inflammatory granulation and chronic cholesteatoma otitis media, which are characterized by a tendency to damage the bone tissue. A total of 293 individuals met the criteria for inclusion in the study. The analysis showed that chronic otitis media with inflammatory granulation had an unfavorable effect on hearing improvement prognosticated postoperatively. Defects in the middle cranial fossa were observed to occur five times more often than defects in the posterior cranial fossa. These defects were usually observed with granulation tissue and rarely with the concurrence of cholesteatoma and granulation tissue. The presence of granulation tissue is an unfavorable prognostic factor for improvement in air and bone conduction. The probability of exposing the dura mater of the brain is higher in cases with granulation tissue than in cases with cholesteatoma.


Criminalizing Sex Work Clients and Rushed Negotiations among Sex Workers Who Use Drugs in a Canadian Setting.
Previous research indicates that criminalization of sex work is associated with harms among sex workers. In 2013, the Vancouver Police Department changed their sex work policy to no longer target sex workers while continuing to target clients and third parties in an effort to increase the safety of sex workers (similar to "end-demand sex work" approaches being adopted in a number of countries globally). We sought to investigate the trends and correlates of rushing negotiations with clients due to police presence among 359 sex workers who use drugs in Vancouver before and after the guideline change. Data were derived from three prospective cohort studies of people who use drugs in Vancouver between 2008 and 2014. We used sex-stratified multivariable generalized estimating equation models. The crude percentages of sex workers who use drugs reporting rushing client negotiations changed from 8.9% before the guideline change to 14.8% after the guideline change among 259 women, and from 8.6 to 7.1% among 100 men. In multivariable analyses, there was a significant increase in reports of rushing client negotiation after the guideline change among women (p = 0.04). Other variables that were independently associated with increased odds of rushing client negotiation included experiencing client-perpetrated violence (among both men and women) and non-heterosexual orientation (among women) (all p < 0.05). These findings indicate that despite the policing guideline change, rushed client negotiation due to police presence appeared to have increased among our sample of female sex workers who use drugs. It was also associated with client-perpetrated violence and other markers of vulnerability. These findings lend further evidence that criminalizing the purchase of sexual services does not protect the health and safety of sex workers.


Abrupt spin transition in a modified-terpyridine cobalt(ii) complex with a highly-distorted [CoN6] core.
The cobalt(ii) complex incorporating π-conjugated substituent, [Co(Naph-C2-terpy)2](BF4)2 (1; Naph-C2-terpy = 4'-(2-naphthoxy(ethoxy))-2,2':6',2''-terpyridine), exhibits an abrupt spin transition (ST) behavior (cooperative factor C = 0.91) while its solvated product, 1·2MeOH, shows gradual spin crossover (SCO) behavior (C = 0.49). Single crystal X-ray structural analyses demonstrated that the octahedral coordination core [CoN6] in 1 shows larger distortion in both high-spin and low-spin states than solvated 1·2MeOH or another two derivatives, [Co(R-terpy)2](BF4)2 (R = 2-naphthyl (2), 9-anthracenyl (3)). The respective distortion parameters (Σ) are compared with those for previously reported SCO cobalt(ii) compounds. The highly-distorted [CoN6] core in 1 (Σ = 126 in the HS state and 101.6 in the LS state) was stabilized by strong intermolecular interactions and observed an abrupt ST behaviour.


Multiple retroviral infection by HTLV type 1, 2, 3 and simian foamy virus in a family of Pygmies from Cameroon.
To better understand the origins and modes of transmission of HTLV-3 and to search for other retroviral infections (HTLV-1, HTLV-2, foamy viruses), we studied the family of a HTLV-3-infected individual (Pyl43), from Cameroon. Thirty-five persons were included. All adult men were still actively hunting nonhuman primates (NHP). All women were also butchering and cutting-up animals. Five persons reported a bite by an NHP. While HTLV-3 infection was only found in Pyl43, HTLV-1 and HTLV-2 infections were found, respectively, in 5 and 9 persons with one being co-infected by both retroviruses. Phylogenetic analysis suggested intra-familial transmission of HTLV-1 subtypes B and D and HTLV-2. One man was infected by a chimpanzee foamy virus, acquired probably 45 years ago, through a bite. Acquisition of retroviral infections still occurs in central Africa involving to various extent not only intra-familial transmission for HTLV-1/HTLV-2 but also direct interspecies transmission from NHP for foamy virus and possibly for HTLV-1 and HTLV-3.


Development of a Compact Rectenna for Wireless Powering of a Head-Mountable Deep Brain Stimulation Device.
Design of a rectangular spiral planar inverted-F antenna (PIFA) at 915 MHz for wireless power transmission applications is proposed. The antenna and rectifying circuitry form a rectenna, which can produce dc power from a distant radio frequency energy transmitter. The generated dc power is used to operate a low-power deep brain stimulation pulse generator. The proposed antenna has the dimensions of 10 mm [Formula: see text]12.5 mm [Formula: see text]1.5 mm and resonance frequency of 915 MHz with a measured bandwidth of 15 MHz at return loss of [Formula: see text]. A dielectric substrate of FR-4 of [Formula: see text] and [Formula: see text] with thickness of 1.5 mm is used for both antenna and rectifier circuit simulation and fabrication because of its availability and low cost. An L-section impedance matching circuit is used between the PIFA and voltage doubler rectifier. The impedance matching circuit also works as a low-pass filter for elimination of higher order harmonics. Maximum dc voltage at the rectenna output is 7.5 V in free space and this rectenna can drive a deep brain stimulation pulse generator at a distance of 30 cm from a radio frequency energy transmitter, which transmits power of 26.77 dBm.


Determining mercury levels in anchovy and in individuals with different fish consumption habits, together with their neurological effects.
An increase in enviromental pollution may lead to mercury toxicity of fish origin due to the accumulative nature of methylmercury in fish. The main sources of human exposure to organic mercury compounds are contaminated fish and other seafoods. This descriptive study was planned to determine mercury levels in anchovy and in hair samples from individuals with different fish consumption habits, and to evaluate those individuals in terms of toxic effects. For that purpose, we analyzed 100 anchovies from the Black Sea and 100 anchovies from the Sea of Marmara, and assessed 25 wholesale workers in fish markets and 25 cleaning firm employees from both Ankara and Istanbul. Mercury levels in samples were measured using a cold vapor atomic absorption spectrophotometer. Participants were examined neurologically and mini mental state examination was applied to evaluate their cognitive functions. Mercury levels in fish were found to be below the national and international permitted levels. There was no statistically significant relation between mercury levels and the sea from which fish were caught. Hair mercury levels for all participants were within permitted ranges. However, hair mercury levels in both cities increased significantly with amount and frequency of fish consumption. A significant correlation was determined at correlation analysis between levels of fish consumption and hair mercury levels in the fishmongers and in the entire group (r = 0.32, p = 0.025; r = 0.23, p = 0.023, respectively). Neurological examination results were normal, except for a decrease in deep tendon reflexes in some participants in both cities. There was no correlation between Standardized Mini Mental State Examination results and hair mercury levels. We conclude that establishing a monitoring system for mercury levels in fish and humans will be useful in terms of evaluating potential neurotoxic effects.


Efficacy of a once-a-week screening programme to control extended-spectrum beta-lactamase-producing bacteria in a neonatal intensive care unit.
Extended-spectrum beta-lactamase (ESBL)-producing bacteria are an escalating problem threatening health. Devastating consequences can result in neonatal intensive care units (NICU) due to these bacteria. The aim of this study was to investigate the efficacy of once-a-week screening (July 2010 to September 2012) versus screening on demand (April 2008 to June 2010). The investigation was an open retrospective descriptive study comparing 2 unpaired groups, the first exposed to screening on demand and the second to screening once a week. All other infection control measures were unchanged. Both groups were cared for in the NICU of Skåne University Hospital. Parameters compared were the proportion of cultured neonates, prevalence, time before detection, number of secondary cases, and clinical infections due to ESBL-producing bacteria. The proportion of cultured neonates increased from 28% to 49% (p < 0.05) in period 2. The time from admission to detection was 8 days shorter in period 2 (p < 0.05). Secondary cases decreased from 44% to 9% (p < 0.05), and clinical infections from 4 to 0 cases (p < 0.05). During period 2, the prevalence of colonization was 1.77%. Once-a-week screening is a strategy to control the epidemiology of unwanted pathogens among newborn infants. It provides the opportunity for early intervention, thereby avoiding secondary cases and infections. Premature neonates in particular benefit from this approach. The prevalence of ESBL of 1.77% is low from an international perspective. ESBL appear to be introduced onto the ward by mothers colonized with ESBL.


Teratogenicity of mycophenolate confirmed in a prospective study of the European Network of Teratology Information Services.
After maternal exposure to mycophenolate in pregnancy a high number of fetal losses and a specific pattern of birth defects consisting of microtia, cleft lip, and other anomalies have been reported. However, so far, prospective data on pregnancy outcome allowing quantitative risk assessment are missing. We report on 57 prospectively ascertained pregnancies after maternal therapy with mycophenolate (mycophenolate mofetil or mycophenolate sodium) identified by European Teratology Information Services (ETIS) through their risk consultation process. The outcome of these prospective pregnancies was as follows: 16 spontaneous abortions, 12 elective terminations of pregnancy (ETOP) (including two late terminations for multiple malformations consistent with mycophenolate embryopathy), and 29 liveborn infants. The probability of spontaneous abortion was about 45% (95% CI 29 to 66%) estimated using survival analysis technique. Six out of 29 live born infants had major congenital defects: Two with external auditory canal atresia (EACA) (with and without microtia), one with tracheo-esophageal atresia, one with severe hydronephrosis, one with an atrial septal defect (ASD) and one with a myelomeningocele. Thus, at least four fetuses/infants of our prospective case series had a clinical phenotype consistent with mycophenolate embryopathy. Our results confirm a high incidence of major malformations (26%) after first trimester exposure to mycophenolate. Apart from exposure to mycophenololate, the underlying maternal disease and concomitant medication may also have contributed to the other poor pregnancy outcomes such as a high rate of spontaneous abortions, prematurity (62%), and low birth weight (31%).


A self-assessment tool for oncology nurses: preliminary implementation and evaluation.
Nurses who fail to identify knowledge gaps in their practice and who do not maintain competence place patients with cancer at risk for adverse events and poor outcomes. Self-assessment tools can assist oncology nurses in identifying knowledge deficits in fundamental oncology concepts. This article describes the development and implementation of a self-assessment tool to assist nurses in maintaining competence to provide safe, effective oncology care. The tool was developed after an examination of relevant literature, collaboration with an oncology team, and consideration of the Oncology Nursing Society's and American Nursing Association's standards of care. Preliminary evaluation suggests it may offer an effective means for oncology nurses to identify knowledge deficits and tailor educational interventions to address identified needs.


The cost-effectiveness of intermittent preventive treatment for malaria in infants in Sub-Saharan Africa.
Intermittent preventive treatment in infants (IPTi) has been shown to decrease clinical malaria by approximately 30% in the first year of life and is a promising malaria control strategy for Sub-Saharan Africa which can be delivered alongside the Expanded Programme on Immunisation (EPI). To date, there have been limited data on the cost-effectiveness of this strategy using sulfadoxine pyrimethamine (SP) and no published data on cost-effectiveness using other antimalarials. We analysed data from 5 countries in sub-Saharan Africa using a total of 5 different IPTi drug regimens; SP, mefloquine (MQ), 3 days of chlorproguanil-dapsone (CD), SP plus 3 days of artesunate (SP-AS3) and 3 days of amodiaquine-artesunate (AQ3-AS3).The cost per malaria episode averted and cost per Disability-Adjusted Life-Year (DALY) averted were modeled using both trial specific protective efficacy (PE) for all IPTi drugs and a pooled PE for IPTi with SP, malaria incidence, an estimated malaria case fatality rate of 1.57%, IPTi delivery costs and country specific provider and household malaria treatment costs. In sites where IPTi had a significant effect on reducing malaria, the cost per episode averted for IPTi-SP was very low, USD 1.36-4.03 based on trial specific data and USD 0.68-2.27 based on the pooled analysis. For IPTi using alternative antimalarials, the lowest cost per case averted was for AQ3-AS3 in western Kenya (USD 4.62) and the highest was for MQ in Korowge, Tanzania (USD 18.56). Where efficacious, based only on intervention costs, IPTi was shown to be cost effective in all the sites and highly cost-effective in all but one of the sites, ranging from USD 2.90 (Ifakara, Tanzania with SP) to USD 39.63 (Korogwe, Tanzania with MQ) per DALY averted. In addition, IPTi reduced health system costs and showed significant savings to households from malaria cases averted. A threshold analysis showed that there is room for the IPTi-efficacy to fall and still remain highly cost effective in all sites where IPTi had a statistically significant effect on clinical malaria. IPTi delivered alongside the EPI is a highly cost effective intervention against clinical malaria with a range of drugs in a range of malaria transmission settings. Where IPTi did not have a statistically significant impact on malaria, generally in low transmission sites, it was not cost effective.


Increased motor vehicle crashes following induced earthquakes in Oklahoma, USA.
Anxiety-inducing life events increase the risk of motor vehicle crashes. We test the hypothesis that earthquakes, known to increase anxiety in the population, also increase the incidence of motor vehicle crashes. Our study took place in Oklahoma, USA where wastewater injection resulted in increased induced seismicity between 2010 and 2016. We identified dates of earthquakes ≥ magnitude 4 (a level felt by most people) with data from the U.S. Geologic Survey. The Oklahoma Highway Safety Office provided county-level monthly vehicle crash counts. We defined high, medium, and low earthquake exposure counties based on the location of earthquake epicenters. Using time-series analyses, we evaluated the association between monthly counts of ≥magnitude 4 earthquakes and motor vehicle crashes by exposure group. Earthquakes ≥ magnitude 4 took place in 38 of 84 study months, and a monthly average of 5813 (SD = 384) crashes occurred between 2010 and 2016. In high-exposure counties, we observed an additional 39.2 motor vehicle crashes per each additional ≥ magnitude 4 earthquake in the prior month (SE = 11.5). We found no association between the timing of ≥magnitude 4 earthquakes and motor vehicle crashes in the medium or low exposure counties. With a binary earthquake exposure variable, we found a 4.6% (SE = 1.4%) increase in motor vehicle crashes in the high exposure counties in the month following 1 or more ≥magnitude 4 earthquakes. Consistent with our hypothesis, there was no association between earthquakes of magnitude ≤ 2.5 and motor vehicle crashes in the high-exposure counties. This novel evidence of an association between induced earthquakes in Oklahoma and motor vehicle crashes warrants future research given the high economic and social costs of such vehicle crashes.


The relationship between body fluid volume, sodium ion concentration, and sensitivity to pressor effect of angiotensin II in dogs.
Extracellular fluid volume, plasma electrolyes, and plasma angiotensin II (A II) were individually controlled to determine their influence on the acute pressor responsiveness to A II. Hemodialysis of nephrectomized dogs was used to simulate and control the changes of major variables which occur in the intact state during changes in sodium balance. A II dose-pressure response curves were determined in 11 dogs at three volume states with plasma [Na+] maintained constant and in five dogs at low, normal, and high plasma [Na+] with body fluid volume maintained constant. Parallel shifts of the log dose-response curves were obtained in the three volume states. The same rise in arterial pressure with identical doses of A II was obtained at normal, contracted, and expanded volume states, with the change of arterial pressure based on the uncompensated basal pressure level at each volume state. When the fall in pressure observed during volume depletion was returned to control levels with norepinephrine, there was no change in the A II dose-response relationship from the control state. No difference in the A II dose-pressure response relationship was obtained between states of 140, 146, and 156 mEq/liter plasma [Na+] with body fluid volume held constant. The studies indicate that short-term alterations in either sodium or water balance do not alter the "real" vascular sensitivity to A II. The "apparent" changes normally observed result from preexisting endogenous levels of circulating A II present at the time the dose-response curve is determined which probably alter the availability of receptor sites to A II.


Increasing species sampling in chelicerate genomic-scale datasets provides support for monophyly of Acari and Arachnida.
Chelicerates are a diverse group of arthropods, represented by such forms as predatory spiders and scorpions, parasitic ticks, humic detritivores, and marine sea spiders (pycnogonids) and horseshoe crabs. Conflicting phylogenetic relationships have been proposed for chelicerates based on both morphological and molecular data, the latter usually not recovering arachnids as a clade and instead finding horseshoe crabs nested inside terrestrial Arachnida. Here, using genomic-scale datasets and analyses optimised for countering systematic error, we find strong support for monophyletic Acari (ticks and mites), which when considered as a single group represent the most biodiverse chelicerate lineage. In addition, our analysis recovers marine forms (sea spiders and horseshoe crabs) as the successive sister groups of a monophyletic lineage of terrestrial arachnids, suggesting a single colonisation of land within Chelicerata and the absence of wholly secondarily marine arachnid orders.


Nanotechnology for the treatment of deep endometriosis: uptake of lipid core nanoparticles by LDL receptors in endometriotic foci.
Rapidly dividing cells in multiple types of cancer and inflammatory diseases undergo high low density lipoprotein (LDL) uptake for membrane synthesis, and coupling an LDL-like nanoemulsion, containing lipid nanoparticles (LDE) to a chemotherapeutic agent efficiently targets these cells without significant systemic effects. This was a prospective exploratory study that evaluated the uptake of a radioactively labeled LDE emulsion by receptors of endometriotic foci and the capacity of the LDE for cellular internalization. The lipid profile of each patient was determined before surgery, and labeled LDE were injected into fourteen patients with intestinal or nonintestinal endometriosis. The radioactivity of each tissue sample (intestinal endometriosis, nonintestinal endometriosis, healthy peritoneum, or topical endometrium) was measured. The group with intestinal endometriosis presented higher levels of plasma LDL but lower LDE uptake by foci than the nonintestinal group, suggesting less cell division and more fibrosis. The uptake of LDE was highest in the topical endometrium, followed by the healthy peritoneum, and lowest in the endometriotic lesion. Since the endometriotic foci showed significant LDE uptake, there was likely increased consumption of LDL by these cells, similar to cells in cancers and inflammatory diseases. Plasma cholesterol levels had no influence on LDE uptake, which showed that the direct delivery of the nanoemulsion to target tissues was independent of serum lipoproteins. There were no significant differences in the parameters (p>0.01) because of the small sample size, but the findings were similar to those of previous studies. Nanotechnology is a promising therapeutic option for surgery and hormonal blockage for deep endometriosis, with a lower complication rate and no systemic side effects.


Task sharing of a psychological intervention for maternal depression in Khayelitsha, South Africa: study protocol for a randomized controlled trial.
Maternal depression carries a major public health burden for mothers and their infants, yet there is a substantial treatment gap for this condition in low-resourced regions such as sub-Saharan Africa. To address this treatment gap, the strategy of "task sharing" has been proposed, involving the delivery of interventions by non-specialist health workers trained and supervised by specialists in routine healthcare delivery systems. Several psychological interventions have shown benefit in treating maternal depression, but few have been rigorously evaluated using a task sharing approach. The proposed trial will be the first randomised controlled trial (RCT) evaluating a task sharing model of delivering care for women with maternal depression in sub-Saharan Africa. The objective of this RCT is to determine the effectiveness and cost-effectiveness of a task sharing counseling intervention for maternal depression in South Africa. The study is an individual-level two-arm RCT. A total of 420 depressed pregnant women will be recruited from two ante-natal clinics in a low-income township area of Cape Town, using the Edinburgh Postnatal Depression Scale to screen for depression; 210 women will be randomly allocated to each of the intervention and control arms. The intervention group will be given six sessions of basic counseling over a period of 3 to 4 months, provided by trained community health workers (CHW)s. The control group will receive three monthly phone calls from a CHW trained to conduct phone calls but not basic counseling. The primary outcome measure is the 17-Item Hamilton Depression Rating Scale (HDRS-17). The outcome measures will be applied at the baseline assessment, and at three follow-up points: 1 month before delivery, and 3 and 12 months after delivery. The primary analysis will be by intention-to-treat and secondary analyses will be on a per protocol population. The primary outcome measure will be analyzed using linear regression adjusting for baseline symptom severity measured using the HDRS-17. The findings of this trial can provide policy makers with evidence regarding the effectiveness and cost-effectiveness of structured psychological interventions for maternal depression delivered by appropriately trained and supervised non-specialist CHWs in sub-Saharan Africa. Clinical Trials (ClinicalTrials.gov): NCT01977326, registered on 24/10/2013; Pan African Clinical Trials Registry (http://www.pactr.org): PACTR201403000676264, registered on 11/10/2013.


18 F-Fluoride positron emission tomography/computed tomography for noninvasive in vivo quantification of pathophysiological bone metabolism in experimental murine arthritis.
Evaluation of disease severity in experimental models of rheumatoid arthritis is inevitably associated with assessment of structural bone damage. A noninvasive imaging technology allowing objective quantification of pathophysiological alterations of bone structure in rodents could substantially extend the methods used to date in preclinical arthritis research for staging of autoimmune disease severity or efficacy of therapeutical intervention. Sodium 18 F-fluoride (18 F-NaF) is a bone-seeking tracer well-suited for molecular imaging. Therefore, we systematically examined the use of 18 F-NaF positron emission tomography/computed tomography (PET/CT) in mice with glucose-6-phosphate isomerase (G6PI)-induced arthritis for quantification of pathological bone metabolism. F-fluoride was injected into mice before disease onset and at various time points of progressing experimental arthritis. Radioisotope accumulation in joints in the fore- and hindpaws was analyzed by PET measurements. For validation of bone metabolism quantified by 18 F-fluoride PET, bone surface parameters of high-resolution μCT measurements were used. Before clinical arthritis onset, no distinct accumulation of 18 F-fluoride was detectable in the fore- and hindlimbs of mice immunized with G6PI. In the course of experimental autoimmune disease, 18 F-fluoride bone uptake was increased at sites of enhanced bone metabolism caused by pathophysiological processes of autoimmune disease. Moreover, 18 F-fluoride signaling at different stages of G6PI-induced arthritis was significantly correlated with the degree of bone destruction. CT enabled identification of exact localization of 18 F-fluoride signaling in bone and soft tissue. The results of this study suggest that small-animal PET/CT using 18 F-fluoride as a tracer is a feasible method for quantitative assessment of pathophysiological bone metabolism in experimental arthritis. Furthermore, the possibility to perform repeated noninvasive measurements in vivo allows longitudinal study of therapeutical intervention monitoring.


Postpartum Endogenous Candida Endophthalmitis.
Postpartum endogenous fungal endophthalmitis in otherwise healthy females is extremely rare disease. We report a case of a 25-year-old female patient referred with a history of decreased vision in her right eye 1 month after uncomplicated vaginal delivery. She presented with multifocal chorioretinal infiltrates. The patient showed persistent inflammation in her right eye then after. Systemic workup was unremarkable apart from a history of vaginal discharge during peripartum period. Vaginal swap confirmed the presence of Candida albicans. Culture of the vitreous sample confirmed the growth of C. albicans. The patient was managed with intravitreal amphotericin B in addition to systemic antifungal treatment followed by pars plana vitrectomy. The patient achieved 20/40 vision with quiet eye after 6 months of follow-up.


Intestinal-type tumour in resected gastric remnant cancer.
Lauren's intestinal type of gastric cancer was proposed to be dependent on long-term environmental factors and is always preceded by chronic premalignant change. A cohort study was performed and demonstrated an increased cancer risk of gastric remnant after gastric surgery for benign disease. It is generally believed that after gastrectomy the residual stomach has an environmental change and, thus, enters a neoplastic process. Based on the carcinogenic theory of intestinal-type tumour, it would be of interest to know whether the intestinal-type tumour is more common in gastric remnant cancer. Forty patients with gastric remnant cancer had gastrectomy in the Veterans General Hospital-Taipei. Another 683 patients with primary gastric carcinoma underwent resection and were used as controls. The clinical characteristics, tumour stage and intestinal-type tumour were analysed in gastric remnant cancer and were compared with the various portions of primary gastric carcinoma. Although the overall distribution of intestinal-type carcinoma in gastric remnant (45%) was no different to that of any other portion of stomach cancer, intestinal-type carcinoma was more common in the early stage of gastric remnant (73%) and distal stomach (73%), but not in the proximal stomach (50%), which was supposed to have the same characteristics as the gastric remnant because of identical anatomic location. More than expected, intestinal-type carcinoma in early gastric remnant cancer together with a long incubation interval between primary surgery and later tumour occurrence were compatible with the theory of carcinogenesis of intestinal-type carcinoma.


Effects of exercise programs to prevent decline in health-related quality of life in highly deconditioned institutionalized elderly persons: a randomized controlled trial.
Our objective was to assess the effects of targeted exercise programs on health-related quality of life compared with usual care based on the ability to perform activities of daily living (ADL) and the Neuropsychiatric Inventory scores in geriatric institutionalized persons. A randomized controlled trial of 2 exercise programs vs usual care was conducted in 160 institutionalized persons 65 years or older who were able to understand basic motor commands and to move from one position to another. Interventions were performed over 6 months and were either an adapted tai chi program (4 times 30 min/wk) or a cognition-action program (2 times 30-45 min/wk) that focused primarily on an adapted guidance of patient-centered communication skills. The control group received usual care. The study was conducted at 4 settings. The main outcomes were changes in health-related quality of life based on ADL and Neuropsychiatric Inventory scores after 12 months. The control group experienced a decline in ADL over the 12-month period compared with the adapted tai chi and cognition-action groups, but the differences were not significant (P = .24 and P = .15, respectively). Also, the components of ADL, eg, ability to walk, continence, and nutrition, were maintained better in the intervention groups than in the control group. The total Neuropsychiatric Inventory score also worsened significantly in the control group, while it was unchanged or improved in the intervention groups. The differences between the cognition-action group and the control group were significant (P > .001). Neuropsychiatric diagnosis subgroups (such as dementia and psychosis) did not show a specific response from any intervention. Adapted exercise programs can slow down the decline in health-related quality of life among heterogeneous, institutionalized elderly persons. clinicaltrials.gov Identifier: NCT00623532.


Plasmon induced transparency in cascaded π-shaped metamaterials.
We experimentally and numerically demonstrate a planar metamaterial consisting of two asymmetrically positioned π-structures in a single unit that exhibits plasmonic analogue of electromagnetically induced transparency (EIT). Through the coupling of the constituent nanorod elements, the proposed structure enables fine spectral tuning of the EIT-like behavior and controlling the location of near field enhancement. Originated from the asymmetric cascaded π-structures, we introduce a more compact system which possesses the EIT-like characteristics and as well as much smaller mode volumes. Due to these properties, the proposed metamaterials can be utilized for a wide range of applications including bio-chemical sensors, optical filters and modulators and enhancement of non-linear processes.


Preventing violence against women and girls in Bihar: challenges for implementation and evaluation.
While there are a growing number of interventions and evaluations of programmes aimed at changing gender norms and violence against women and girls, there remains a dearth of documentation outlining the challenges faced in conducting these interventions and evaluations, particularly in traditional and low literacy settings. The Do Kadam Barabari Ki Ore (Two Steps Towards Equality) programme sought to understand what works to prevent violence against women and girls in Bihar, India. This paper draws insights from process evaluation data. It describes promising features and challenges of implementation, and characteristics which weaken the potential effects of complex, community based, social sector programmes that aim to change deeply entrenched gender power hierarchies. We drew on the Medical Research Council framework for process evaluation in analysing our process evaluation data, and focus on mechanisms of impact, and factors inhibiting programme success, including contextual and implementation challenges. The paper also outlines measures that may help overcome observed challenges and areas that require modifications and/or further investigation. The programme experienced several challenges. These included contextual issues, such as the lack of leadership skills of those delivering the intervention and the gap between expected responsibilities and activities of government platforms and reality. Implementation challenges were encountered in reaching men and boys, younger women and the community at large and ensuring their regular attendance; and in maintaining the fidelity of the intervention activities. Our insights call for an evidence-supported dialogue on these challenges and how best to anticipate and address them.


Functional Parameters Derived from Magnetic Resonance Imaging Reflect Vascular Morphology in Preclinical Tumors and in Human Liver Metastases.
Purpose: Tumor vessels influence the growth and response of tumors to therapy. Imaging vascular changes in vivo using dynamic contrast-enhanced MRI (DCE-MRI) has shown potential to guide clinical decision making for treatment. However, quantitative MR imaging biomarkers of vascular function have not been widely adopted, partly because their relationship to structural changes in vessels remains unclear. We aimed to elucidate the relationships between vessel function and morphology in vivo Experimental Design: Untreated preclinical tumors with different levels of vascularization were imaged sequentially using DCE-MRI and CT. Relationships between functional parameters from MR (iAUC, K trans, and BATfrac) and structural parameters from CT (vessel volume, radius, and tortuosity) were assessed using linear models. Tumors treated with anti-VEGFR2 antibody were then imaged to determine whether antiangiogenic therapy altered these relationships. Finally, functional-structural relationships were measured in 10 patients with liver metastases from colorectal cancer.Results: Functional parameters iAUC and K trans primarily reflected vessel volume in untreated preclinical tumors. The relationships varied spatially and with tumor vascularity, and were altered by antiangiogenic treatment. In human liver metastases, all three structural parameters were linearly correlated with iAUC and K trans For iAUC, structural parameters also modified each other's effect.Conclusions: Our findings suggest that MR imaging biomarkers of vascular function are linked to structural changes in tumor vessels and that antiangiogenic therapy can affect this link. Our work also demonstrates the feasibility of three-dimensional functional-structural validation of MR biomarkers in vivo to improve their biological interpretation and clinical utility. Clin Cancer Res; 24(19); 4694-704. ©2018 AACR.


Self-reported psychological states and physiological responses to different types of motivational general imagery.
The aim of the present study was to examine self-reported psychological states and physiological responses (heart rate) experienced during different motivational general imagery scenarios. Forty competitive athletes wore a standard heart rate monitor and imaged five scripts (mastery, coping, anxiety, psyching up, and relaxation). Following each script, they reported their state anxiety and self-confidence. A significant increase in heart rate from baseline to imagery was found for the anxiety, psyching-up, and coping imagery scripts. Furthermore, the intensity of cognitive and somatic anxiety was greater and perceived as being more debilitative following the anxiety imagery script. The findings support Lang's (1977, 1979) proposal that images containing response propositions will produce a physiological response (i.e., increase heart rate). Moreover, coping imagery enabled the athletes to simultaneously experience elevated levels of anxiety intensity and thoughts and feelings they perceived as helpful.


Poverty and Blindness in Nigeria: Results from the National Survey of Blindness and Visual Impairment.
Poverty can be a cause and consequence of blindness. Some causes only affect the poorest communities (e.g. trachoma), and poor individuals are less likely to access services. In low income countries, cataract blind adults have been shown to be less economically active, indicating that blindness can exacerbate poverty. This study aims to explore associations between poverty and blindness using national survey data from Nigeria. Participants ≥40 years were examined in 305 clusters (2005-2007). Sociodemographic information, including literacy and occupation, was obtained by interview. Presenting visual acuity (PVA) was assessed using a reduced tumbling E LogMAR chart. Full ocular examination was undertaken by experienced ophthalmologists on all with PVA <6/12 in either eye. Causes of vision loss were determined using World Health Organization guidelines. Households were categorized into three levels of poverty based on literacy and occupation at household level. A total of 569/13,591 participants were blind (PVA <3/60, better eye; prevalence 4.2%, 95% confidence interval [CI] 3.8-4.6%). Prevalences of blindness were 8.5% (95% CI 7.7-9.5%), 2.5% (95% CI 2.0-3.1%), and 1.5% (95% CI 1.2-2.0%) in poorest, medium and affluent households, respectively (p = 0.001). Cause-specific prevalences of blindness from cataract, glaucoma, uncorrected aphakia and corneal opacities were significantly higher in poorer households. Cataract surgical coverage was low (37.2%), being lowest in females in poor households (25.3%). Spectacle coverage was 3 times lower in poor than affluent households (2.4% vs. 7.5%). In Nigeria, blindness is associated with poverty, in part reflecting lower access to services. Reducing avoidable causes will not be achieved unless access to services improves, particularly for the poor and women.


Innate Immune Responses to RSV Infection Facilitated by OGG1, an Enzyme Repairing Oxidatively Modified DNA Base Lesions.
The primary cause of morbidity and mortality from infection with respiratory syncytial virus (RSV) is the excessive innate immune response(s) (IIR) in which reactive oxygen species (ROS) play key role(s). However, the mechanisms for these processes are not fully understood. We hypothesized that expressions of IIR genes are controlled by the ROS-generated epigenetic-like mark 7,8-dihydro-8-oxo(d)guanine (8-oxo(d)Gua) and 8-oxoguanine DNA glycosylase1 (OGG1). Here, we report that ROS not only generates intrahelical 8-oxo(d)Gua, but also enzymatically disables OGG1 in RSV-infected human airway epithelial cells and mouse lungs. OGG1 bound to 8-oxo(d)Gua in gene regulatory sequences promotes expression of IIR genes, and consequently exacerbates lung inflammation, histological changes, and body weight loss of experimental animals. Pharmacological inhibition of OGG1 substrate binding decreased expression of RSV-induced chemokine and cytokines and significantly lessened clinical symptoms. Results of mechanistic studies show that OGG1 binding at 8-oxo(d)Gua promoter regions modulated loading of transcription factors via transient cooperative interactions in RSV-infected lungs and airway epithelial cells. Other base specific DNA repair proteins had no effects. Collectively, this study identifies unprecedented roles of ROS-generated DNA base lesion(s) and cognate repair protein as a determinant of RSV-induced exuberant inflammation. Pharmaceutical inhibition of OGG1 interaction with its DNA substrate may represent a novel strategy in prevention/intervention of respiratory viral infections.


Human resources for health through conflict and recovery: lessons from African countries.
A protracted conflict affects human resources for health (HRH) in multiple ways. In most cases, the inflicted damage constitutes the main obstacle to health sector recovery. Interventions aimed at healing derelict human resources are however fraught with difficulties of a political, technical, financial and administrative order. The experience accumulated in past recovery processes has made some important players aware of the cost incurred by neglecting human resource development. Several transitions from conflict to peace have been documented, even if largely in unpublished reports. This paper presents condensed descriptions of some African HRH-related recovery processes, which provide useful lessons. The technical work demanded to resuscitate a derelict health workforce is fairly well understood. In most situations, the highest hurdles lie outside of the health domain, and are of a political and administrative nature. Success stories are rare. But useful lessons are taught by failure as well as by success.


Camden active spaces: does the construction of active school playgrounds influence children's physical activity levels? A longitudinal quasi-experiment protocol.
Physical activity is essential for every facet of children's health. However, physical activity levels in British children are low. The school environment is a promising setting to increase children's physical activity but limited empirical evidence exists on how a change in the outdoor physical school environment influences physical activity behaviour. The London Borough of Camden is redesigning seven existing school playgrounds to engage children to become more physically active. The primary aim of this project is to evaluate the impact of the redesigned playgrounds on children's physical activity, well-being and physical function/fitness. This project will use a longitudinal quasi-experimental design. Seven experimental schools and one control school will take part. One baseline data collection session and two follow-ups will be carried out. Between baseline and follow-up, the experimental school playgrounds will be redesigned. At baseline, a series of fitness tests, anthropometric and questionnaire measurements, and 7-day objective physical activity monitoring (Actigraph accelerometer) will be carried out on children (aged 5–16 years). This will be repeated at follow-up. Changes in overall physical activity levels and levels during different times of the day (eg, school breaks) will be examined. Multilevel regression modelling will be used to analyse the data. The results of this study will be disseminated through peer-review publications and scientific presentations. Ethical approval was obtained through the University College London Research Ethics Committee (Reference number: 4400/002).


Crystalloid to packed red blood cell transfusion ratio in the massively transfused patient: when a little goes a long way.
Massive transfusion (MT) protocols have emphasized the importance of ratio-based transfusion of plasma and platelets relative to packed red blood cells (PRBCs); however, the risks attributable to crystalloid resuscitation in patients requiring MT remain largely unexplored. We hypothesized that an increased crystalloid:PRBC (C:PRBC) ratio would be associated with increased morbidity and poor outcome after MT. Data were obtained from a multicenter prospective cohort study evaluating outcomes in blunt injured adults with hemorrhagic shock. Patients requiring MT (≥ 10 units PRBCs in first 24 hours) were analyzed. The C:PRBC ratio was computed by the ratio of crystalloid infused in liters (L) to the units of PRBCs transfused in the first 24 hours postinjury. Logistic regression modeling was used to characterize the independent risks associated with the 24-hour C:PRBC ratio, after controlling for important confounders and other blood component transfusion requirements. Logistic regression revealed that the 24-hour C:PRBC ratio was significantly associated with a greater independent risk of multiple organ failure (MOF), acute respiratory distress syndrome (ARDS), and abdominal compartment syndrome (ACS). No association with mortality or nosocomial infection was found. A dose-response analysis revealed that patients with a C:PRBC ratio >1.5:1 had over a 70% higher independent risk of MOF and over a twofold higher risk of ARDS and ACS. In patients requiring MT, crystalloid resuscitation in a ratio greater than 1.5:1 per unit of PRBCs transfused was independently associated with a higher risk of MOF, ARDS, and ACS. These results suggest overly aggressive crystalloid resuscitation should be minimized in these severely injured patients. Further research is required to determine whether incorporation of the C:PRBC ratio into MT protocols improves outcome.


The influence of body mass on calculation of power during lower-body resistance exercises.
The objective of this investigation was to examine the influence of body mass in the calculation of power and the subsequent effect on the load-power relationship in the jump squat, squat, and power clean. Twelve Division I male athletes were evaluated on their performance across various intensities in all the 3 lifts. Power output was calculated using 3 separate techniques: (a) including the contribution of body mass in force output (IBM), (b) including the contribution of the mass of body less the mass of the shanks and feet in force output (IBMS), and (c) excluding the contribution of body mass in force output (EBM). Peak power, peak power relative to body mass, and peak force calculated using EBM were significantly (p < or = 0.05) lower than outputs calculated with IBM and IBMS. The load that maximized power output was unchanged between the 3 techniques in the jump squat (0% 1 repetition maximum [1RM]) and power clean (80% 1RM) but was shifted from 56% (IBM and IBMS) to 71% 1RM (EBM) in the squat. Across all 3 movements, the shape of the load-power curve was affected when derived via the EBM method as a result of the underrepresentation of power output at light loads. This was due to the majority of the load being neglected when the mass of the body was removed from the system mass used in the calculation of force. This study indicates that not only is the actual power output significantly lower when body mass is excluded from the force output of a lower body movement, but the load-power relationship is altered as well. Therefore, it is imperative that the mass of the individual being tested is incorporated into the calculation of force used to determine power output during lower-body movements.


Synchronized photonic modulators driven by surface acoustic waves.
Photonic modulators are one of the most important elements of integrated photonics. We have designed, fabricated, and characterized a tunable photonic modulator consisting of two 180°-dephased output waveguide channels, driven by a surface acoustic wave in the GHz frequency range built on (Al,Ga)As. Odd multiples of the fundamental driven frequency are enabled by adjusting the applied acoustic power. A good agreement between theory and experimental results is achieved. The device can be used as a building block for more complex integrated functionalities and can be implemented in several material platforms.


Effect of pumpkin-seed oil on the level of free radical scavengers induced during adjuvant-arthritis in rats.
Pumpkin-seed oil (PSO), a natural supplement rich with antioxidant ingredients, was given to rats in which arthritis was induced using Freund's complete adjuvant. Its effect was compared with that of indomethacin, as a classical anti-inflammatory agent. Two experimental patterns were studied, an acute phase that was applied only with PSO and a chronic phase applied for both PSO and indomethacin. Compared to normal untreated rats, it was shown that the induction of arthritis caused a decrease in serum sulphhydryl groups, with an increase in serum ceruloplasmin in both phases. Blood glutathione was first elevated in the acute phase, then its level was reduced in the chronic phase. Serum N-acetyl-beta-D-glucosaminidase activity was elevated only at the acute phase, while plasma total proteins and albumin were reduced at the chronic phase. Liver glucose-6-phosphate dehydrogenase activity was markedly increased, while no changes were observed in the levels of liver lipid peroxides and glutathione. These changes in the studied parameters were attributed to the superoxides and free radicals during arthritic inflammation. Administration of PSO succeeded in modulating most of the altered parameters affected during arthritis, especially at the chronic phase. Also, a remarkable inhibition of paw oedema was observed. A similar pattern was obtained upon treatment with indomethacin except that indomethacin markedly elevated liver lipid peroxides levels. Concurrent administration of PSO with indomethacin caused no changes in the parameters studied compared to that induced by treatment with indomethacin alone.


Differential kinetics and inhibition of purified recombinant tyrosine kinase 2 (TYK-2) and its catalytic domain JH-1.
The Janus kinase (JAK) family consists of four members: JAK-1, -2, -3 and tyrosine kinase 2 (TYK-2). Recent work suggests that cytokine signaling through TYK-2 may play a critical role in a number of inflammatory processes. We recently described the purification and characterization of phosphorylated isoforms of the TYK-2 kinase domain (TYK-2 KD) and its high resolution 3D structure in the presence of inhibitors. We now report the expression and a two-step purification procedure for the doubly tagged full-length construct, H6-FL-TYK-2-FLAG, and examine its properties compared to those of TYK-2 KD. In the presence of ATP and a peptide substrate, H6-FL-TYK-2-FLAG showed a marked lag in phosphopeptide product formation, while TYK-2 KD showed no such lag. This lag could be eliminated by ATP pretreatment, suggesting that the H6-FL-TYK-2-FLAG enzyme was activated by phosphorylation. The potencies of several nanomolar inhibitors were similar for TYK-2 KD and H6-FL-TYK-2-FLAG. However, these same inhibitors were about 1000 times less potent inhibiting the autophosphorylation of H6-FL-TYK-2-FLAG than they were inhibiting the phosphorylation of a peptide substrate modeled after the activation loop sequence of TYK-2. This intriguing result suggests that autophosphorylation and, thus, activation of H6-FL-TYK-2-FLAG is relatively insensitive to inhibition and that present inhibitors act to inhibit TYK-2 subsequent to activation. Inhibition of TYK-2 autophosphorylation may represent a new area of investigation for the JAK family.


Transcriptomics of cortical gray matter thickness decline during normal aging.
We performed a whole-transcriptome correlation analysis, followed by the pathway enrichment and testing of innate immune response pathway analyses to evaluate the hypothesis that transcriptional activity can predict cortical gray matter thickness (GMT) variability during normal cerebral aging. Transcriptome and GMT data were available for 379 individuals (age range=28-85) community-dwelling members of large extended Mexican American families. Collection of transcriptome data preceded that of neuroimaging data by 17 years. Genome-wide gene transcriptome data consisted of 20,413 heritable lymphocytes-based transcripts. GMT measurements were performed from high-resolution (isotropic 800 μm) T1-weighted MRI. Transcriptome-wide and pathway enrichment analysis was used to classify genes correlated with GMT. Transcripts for sixty genes from seven innate immune pathways were tested as specific predictors of GMT variability. Transcripts for eight genes (IGFBP3, LRRN3, CRIP2, SCD, IDS, TCF4, GATA3, and HN1) passed the transcriptome-wide significance threshold. Four orthogonal factors extracted from this set predicted 31.9% of the variability in the whole-brain and between 23.4 and 35% of regional GMT measurements. Pathway enrichment analysis identified six functional categories including cellular proliferation, aggregation, differentiation, viral infection, and metabolism. The integrin signaling pathway was significantly (p<10(-6)) enriched with GMT. Finally, three innate immune pathways (complement signaling, toll-receptors and scavenger and immunoglobulins) were significantly associated with GMT. Expression activity for the genes that regulate cellular proliferation, adhesion, differentiation and inflammation can explain a significant proportion of individual variability in cortical GMT. Our findings suggest that normal cerebral aging is the product of a progressive decline in regenerative capacity and increased neuroinflammation.


A new PDAC mouse model originated from iPSCs-converted pancreatic cancer stem cells (CSCcm).
Pancreatic ductal adenocarcinoma (PDAC) is the most representative form of pancreatic cancers. PDAC solid tumours are constituted of heterogeneous populations of cells including cancer stem cells (CSCs), differentiated cancer cells, desmoplastic stroma and immune cells. The identification and consequent isolation of pancreatic CSCs facilitated the generation of genetically engineered murine models. Nonetheless, the current models may not be representative for the spontaneous tumour occurrence. In the present study, we show the generation of a novel pancreatic iPSC-converted cancer stem cell lines (CSCcm) as a cutting-edge model for the study of PDAC. The CSCcm lines were achieved only by the influence of pancreatic cancer cell lines conditioned medium and were not subjected to any genetic manipulation. The xenografts tumours from CSCcm lines displayed histopathological features of ADM, PanIN and PDAC lesions. Further molecular characterization from RNA-sequencing analysis highlighted primary culture cell lines (1st CSCcm) as potential candidates to represent the pancreatic CSCs and indicated the establishment of the pancreatic cancer molecular pattern in their subsequent progenies 2nd CSCcm and 3rd CSCcm. In addition, preliminary RNA-seq SNPs analysis showed that the distinct CSCcm lines did not harbour single point mutations for the oncogene Kras codon 12 or 13. Therefore, PDAC-CSCcm model may provide new insights about the actual occurrence of the pancreatic cancer leading to develop different approaches to target CSCs and abrogate the progression of this fatidic disease.


[Neck pain: which physical therapies are recommended ?]
Different physical therapies for cervicalgia are described, as well as their efficacy, adverse effects, degree of evidence and recommendations. Several guidelines recommend active exercise, patient education and various treatments described here. According to the strict criteria of evidence-based medicine, active exercise, dry needling and probably laser therapy are effective as well as acupuncture. The use of a collar-neck brace is not recommended as first intention and should be limited in duration. Despite their clinical benefit and the inclusion of many therapies in several high-level scientific guidelines, the level of evidence of the recommendations could be enhanced by new research.


Evaluating environmental change and behavioral decision-making for sustainability policy using an agent-based model: A case study for the Smoky Hill River Watershed, Kansas.
Sustainability has been at the forefront of the environmental research agenda of the integrated anthroposphere, hydrosphere, and biosphere since the last century and will continue to be critically important for future environmental science. However, linking humans and the environment through effective policy remains a major challenge for sustainability research and practice. Here we address this gap using an agent-based model (ABM) for a coupled natural and human systems in the Smoky Hill River Watershed (SHRW), Kansas, USA. For this freshwater-dependent agricultural watershed with a highly variable flow regime influenced by human-induced land-use and climate change, we tested the support for an environmental policy designed to conserve and protect fish biodiversity in the SHRW. We develop a proof of concept interdisciplinary ABM that integrates field data on hydrology, ecology (fish richness), social-psychology (value-belief-norm) and economics, to simulate human agents' decisions to support environmental policy. The mechanism to link human behaviors to environmental changes is the social-psychological sequence identified by the value-belief-norm framework and is informed by hydrological and fish ecology models. Our results indicate that (1) cultural factors influence the decision to support the policy; (2) a mechanism modifying social-psychological factors can influence the decision-making process; (3) there is resistance to environmental policy in the SHRW, even under potentially extreme climate conditions; and (4) the best opportunities for policy acceptance were found immediately after extreme environmental events. The modeling approach presented herein explicitly links biophysical and social science has broad generality for sustainability problems.


Assessment of inpatient psychiatric readmission risk among patients discharged on an antipsychotic polypharmacy regimen: A retrospective cohort study.
Patients are frequently prescribed multiple antipsychotic medications, leading to higher healthcare costs and increased risk for side effects. The efficacy of multiple versus single antipsychotics to prevent acute relapse, measured by incidence of inpatient readmission, is investigated in Arizona, USA. A retrospective chart review compared socio-demographic and clinical data from 1,010 patients discharged on a single and 377 discharged on multiple antipsychotic medications. Case management records were reviewed for readmission within one year of discharge. Younger age, diagnosis of Schizophrenia or Schizoaffective Disorder, prescription of mood stabilizer, shorter length of stay, and discharge to residential treatment or crisis recovery unit were associated with multiple antipsychotics at discharge. Readmission rates of the single (13.7%) versus multiple (15.9%) antipsychotic groups were not statistically different (p=0.286). Logistic regression analysis established that only age (younger) and the prescription of a mood stabilizer at discharge were significant predictors for increased risk for readmission (p=0.010 and p=0.049, respectively). A Cox survival analysis supported these findings. Concomitant antipsychotic polypharmacy at discharge did not reduce readmission risk over a one-year period. Given the increased risk of side effects and financial costs of polypharmacy, this study did not provide evidence to support this practice. Strikingly, only two variables predicted readmission risk, younger age and prescription of mood stabilizer. Although practitioners should follow practice guidelines more closely to prevent unnecessary exposure to potentially lethal side effects of antipsychotic polypharmacy, further studies are needed to better identify patients at high risk for readmission.


The Use of Filgrastim in Patients with Hodgkin Lymphoma Receiving ABVD.
Background: There is conflicting data about the increased risk of pulmonary toxicity when granulocyte-stimulating factor (G-CSF) is given in combination with bleomycin. No clear consensus for management of patients with Hodgkin lymphoma (HL) who require G-CSF support exists. Our objective was to evaluate whether there is an increase in pulmonary toxicity in patients who receive bleomycin and G-CSF during treatment for HL. Materials and Methods: We conducted a single-center retrospective analysis of patients with Hodgkin Lymphoma from January 2003 until July 2015. All patients who received at least 1 dose of bleomycin and followed at our institution were included. Patients were evaluated for pulmonary toxicity starting from the day of first dose of bleomycin until 1 year after initiation of bleomycin. Data on pre-identified risk factors for pulmonary toxicity were also collected. Results: Fifty-four patients met inclusion criteria. Twenty-one patients received bleomycin alone, and 33 patients received bleomycin and G-CSF. There was no statistically significant (p = 0.50) difference in the development of pulmonary toxicity between the two groups. Crude hazard ratio for development of pulmonary toxicity in the bleomycin and G-CSF cohort was 1.58 (95% confidence interval, CI: 0.41-6.12). On multivariate analysis, the hazard ratio for development of pulmonary toxicity was 1.71 (95% CI: 0.43-6.81). Conclusion: This study does not find evidence that the combination of bleomycin and G-CSF increases the risk for bleomycin- induced pulmonary toxicity. We recommend G-CSF use in HL patients receiving bleomycin when needed to maintain dose intensity.


Prevalence, Risk Factors, and Levels of Burnout Among Oncology Nurses: A Systematic Review.
To determine (a) the average levels of emotional exhaustion (EE), depersonalization (D), and personal accomplishment (PA) among oncology nurses; (b) the prevalence of low, medium, and high levels of burnout for each dimension; and (c) the risk factors for burnout. . A systematic review was carried out using the CUIDEN, CINAHL®, LILACS, ProQuest, PubMed, SciELO, and Scopus databases. . The 436 search results obtained were reduced to a final sample of 27 articles after applying the inclusion and exclusion criteria. . With respect to levels of burnout, published results differ in their conclusions. In general, they indicate that oncology nurses feel little sense of PA and suffer from EE, although few signs of D exist. . Oncology nurses present high levels of EE and of reduced PA. A large proportion of these nurses are at risk of developing burnout. Age, work experience, workload, and communication skills are among the factors that may influence development of the syndrome. . Programs should be developed to identify interventions that would reduce EE and enhance feelings of PA. In addition, risk factors and protective measures should be studied more comprehensively.


Ionic liquids with thioether motifs as synthetic cationic lipids for gene delivery.
This study introduces a novel class of imidazolium- and ammonium-based ionic liquids possessing two C12 and C14 tails and thioether linkers designed for lipoplex-mediated DNA delivery. Imidazolium-based ionic liquids displayed efficient gene delivery properties with low toxicity. Thiol-yne click chemistry was employed for the facile and robust synthesis of these thioether-based cationic lipioids with enhanced lipophilicity and low fluidity.


Culture, the 'sick role' and the consumption of health.
This paper revisits Parsons's conception of the 'sick role' and examines the relevance of his writings on the cultural understanding of sickness to the consumption of health in the contemporary era. In terms of current developments, I focus on the development of pro-active approaches towards the healthy body, and the growth of 'information rich' consumers of health care. These have become prominent themes in sociology, and while Parsons's writings are usually viewed as anachronistic I argue they remain highly pertinent to understanding the emergence of informed, body conscious lay people. If Parsons's analysis of health is more relevant to current circumstances than many critics assume, however, it is not unproblematic. The residual categories associated with the sick role obscure the continued utility of his work on the general cultural values informing health care. It is Parsons's analysis of these values, I suggest, that needs rescuing from restricted understandings of the sick role and highlighting as an important resource for contemporary theorists.