Agricultural biodiversity, social-ecological systems and sustainable diets.
The stark observation of the co-existence of undernourishment, nutrient deficiencies and overweight and obesity, the triple burden of malnutrition, is inviting us to reconsider health and nutrition as the primary goal and final endpoint of food systems. Agriculture and the food industry have made remarkable advances in the past decades. However, their development has not entirely fulfilled health and nutritional needs, and moreover, they have generated substantial collateral losses in agricultural biodiversity. Simultaneously, several regions are experiencing unprecedented weather events caused by climate change and habitat depletion, in turn putting at risk global food and nutrition security. This coincidence of food crises with increasing environmental degradation suggests an urgent need for novel analyses and new paradigms. The sustainable diets concept proposes a research and policy agenda that strives towards a sustainable use of human and natural resources for food and nutrition security, highlighting the preeminent role of consumers in defining sustainable options and the importance of biodiversity in nutrition. Food systems act as complex social-ecological systems, involving multiple interactions between human and natural components. Nutritional patterns and environment structure are interconnected in a mutual dynamic of changes. The systemic nature of these interactions calls for multidimensional approaches and integrated assessment and simulation tools to guide change. This paper proposes a review and conceptual modelling framework that articulate the synergies and tradeoffs between dietary diversity, widely recognised as key for healthy diets, and agricultural biodiversity and associated ecosystem functions, crucial resilience factors to climate and global changes.


Fever and Erythema are Specific Findings in Detecting Infection Following Total Knee Arthroplasty.
Current diagnostic modalities are based almost exclusively on laboratory findings and the role of clinical presentation remains unknown. The purpose of this study was to examine the diagnostic value of clinical presentation in detecting periprosthetic joint infection (PJI). This study evaluated 279 patients undergoing revision surgery for failed total knee arthroplasty (TKA) between 2001-2016. Patients were classified as undergoing septic revisions based on major MSIS criteria. Aseptic revisions were defined as cases of single stage revision that did not have suspected PJI, fulfill MSIS criteria, or subsequently fail within one year of follow-up. Clinical presentation included pain, fever, presence of joint effusion or erythema, and reduced range of motion. Serum and synovial laboratory markers were also evaluated. The diagnostic value of each test was assessed and a Fagan's nomogram was constructed. A subset of MSIS-negative patients was used to demonstrate the value of various clinical presentations in detecting PJI. Post-test probability for infection was calculated taking into account clinical presentation together with serum and synovial markers. Our results show that fever and erythema are the most important signs for diagnosing PJI with a positive likelihood ratio (LR) of 10.78 and 8.08, respectively. Effusion had a LR of 2.42. Pain and reduced ROM were not as strongly correlated with PJI diagnosis; LR was 1.02 and 1.51. Of the 35 MSIS-negative patients treated for PJI, 33 had a post-test probability of infection greater than 90% when taking clinical presentation into account. Clinical presentation should be used to guide which future diagnostic tests should be ordered and in the interpretation of their results. Our results indicate that pain, fever, presence of joint effusion or erythema, and reduced range of motion should prompt further workup for infection. We propose a nomogram that may be used in interoperating their individual weight together with laboratory findings. Fever and erythema are highly specific findings in patients with PJI and future studies should assess whether they may be added as minor criteria to current definitions for infection.


Nanoscale electrical property studies of individual GeSi quantum rings by conductive scanning probe microscopy.
The nanoscale electrical properties of individual self-assembled GeSi quantum rings (QRs) were studied by scanning probe microscopy-based techniques. The surface potential distributions of individual GeSi QRs are obtained by scanning Kelvin microscopy (SKM). Ring-shaped work function distributions are observed, presenting that the QRs' rim has a larger work function than the QRs' central hole. By combining the SKM results with those obtained by conductive atomic force microscopy and scanning capacitance microscopy, the correlations between the surface potential, conductance, and carrier density distributions are revealed, and a possible interpretation for the QRs' conductance distributions is suggested.


Neuroendocrine peptides in the prostate.
Circulating androgens are required for normal growth and maintenance of function of the prostate. However, the prostate also contains neuroendocrine peptides, found either in nerve terminals or in prostatic neuroendocrine cells, which are likely to regulate prostate growth or function. The neuronal peptides are likely to participate in the regulation of the synthesis and secretion of prostatic secretory products. While the function of the neuroendocrine cells is undefined, there is evidence for growth-regulating effects of several neuroendocrine cell peptides. Since neuroendocrine differentiation has been correlated with tumor grade and poor prognosis in prostate cancer, the peptide products of the neuroendocrine cells may influence cancer cell replication as well. Recent evidence in other tissues suggests that peptide hormone receptor second-messenger systems may interact with steroid receptors to modulate their actions. These findings raise the possibility that prostatic neuroendocrine peptides may modulate the response of prostate to androgens.


Global map of the prevalence of symptoms of rhinoconjunctivitis in children: The International Study of Asthma and Allergies in Childhood (ISAAC) Phase Three.
Phase One of the International Study of Asthma and Allergies in Childhood (ISAAC) measured the global patterns of prevalence and severity of symptoms of rhinoconjunctivitis in children in 1993-1997. International Study of Asthma and Allergies in Childhood Phase Three was a cross-sectional survey performed 5-10 years after Phase One using the same methodology. Phase Three covered all of the major regions of the world and involved 1 059 053 children of 2 age groups from 236 centres in 98 countries. The average overall prevalence of current rhinoconjunctivitis symptoms was 14.6% for the 13- to 14-year old children (range 1.0-45%). Variation in the prevalence of severe rhinoconjunctivitis symptoms was observed between centres (range 0.0-5.1%) and regions (range 0.4% in western Europe to 2.3% in Africa), with the highest prevalence being observed mainly in the centres from middle and low income countries, particularly in Africa and Latin America. Co-morbidity with asthma and eczema varied from 1.6% in the Indian sub-continent to 4.7% in North America. For 6- to 7-year old children, the average prevalence of rhinoconjunctivitis symptoms was 8.5%, and large variations in symptom prevalence were also observed between regions, countries and centres. Wide global variations exist in the prevalence of current rhinoconjunctivitis symptoms, being higher in high vs low income countries, but the prevalence of severe symptoms was greater in less affluent countries. Co-morbidity with asthma is high particularly in Africa, North America and Oceania. This global map of symptom prevalence is of clinical importance for health professionals.


Effects of prizidilol (SKF 92657) on blood pressure, haemodynamics, sympathetic nervous system activity and plasma volume in essential hypertension.
1. The antihypertensive effect of 4 weeks' treatment with prizidilol (SKF 92657) (mean dosage 520 mg once or twice daily) was studied in ten essential hypertensive patients. 2. Both systolic and diastolic blood pressure were significantly reduced in all cases. Supine heart rate did not change, and in the erect position heart rate was significantly lowered. 3. Blood pressure reduction was due to peripheral vasodilatation, as the cardiac index increased after 4 weeks of prizidilol treatment. 4. After prizidilol plasma noradrenaline and adrenaline increased significantly, and PRA and plasma aldosterone were reduced. Although plasma volume increased, body weight did not change. 5. Cardiac performance, as evaluated by the PEP/LVET ratio, improved after treatment with prizidilol.


Further evidence for the existence of a dual-Cu+ site in MFI working as the efficient site for C2H6 adsorption at room temperature.
We have recently clarified the following point: a dual-type site, which is composed of a pair of monovalent copper ions (Cu(+)) formed in a copper-ion-exchanged MFI-type zeolite (CuMFI), functions as the active center for strong ethane (C2H6) adsorption even at room temperature rather than a single-type site composed of a Cu(+) ion. However, the character of the dual-Cu(+) site in a CuMFI is not yet fully understood. In this study, we have elucidated the nature of the active sites for C2H6 based on infrared (IR) and calorimetric data. On the basis of the results obtained, we came to the conclusion that the dual-Cu(+) site composed of Cu(+) ions giving the adsorption energy of 100 kJ mol(-1) and the absorption band at 2151 cm(-1) for carbon monoxide (used as a probe molecule) at room temperature functions as an adsorption site for C2H6. We also evaluated, for the first time, the interaction between the dual-Cu(+) site and C2H6 energetically, by the direct measurement of heat of adsorption. The value of 67 kJ mol(-1) that we recorded was higher than that for the single-Cu(+) site in this sample and also for other samples, such as NaMFI and HMFI.


A Multiparameter Pressure-Temperature-Humidity Sensor Based on Mixed Ionic-Electronic Cellulose Aerogels.
Pressure (P), temperature (T), and humidity (H) are physical key parameters of great relevance for various applications such as in distributed diagnostics, robotics, electronic skins, functional clothing, and many other Internet-of-Things (IoT) solutions. Previous studies on monitoring and recording these three parameters have focused on the integration of three individual single-parameter sensors into an electronic circuit, also comprising dedicated sense amplifiers, signal processing, and communication interfaces. To limit complexity in, e.g., multifunctional IoT systems, and thus reducing the manufacturing costs of such sensing/communication outposts, it is desirable to achieve one single-sensor device that simultaneously or consecutively measures P-T-H without cross-talks in the sensing functionality. Herein, a novel organic mixed ion-electron conducting aerogel is reported, which can sense P-T-H with minimal cross-talk between the measured parameters. The exclusive read-out of the three individual parameters is performed electronically in one single device configuration and is enabled by the use of a novel strategy that combines electronic and ionic Seebeck effect along with mixed ion-electron conduction in an elastic aerogel. The findings promise for multipurpose IoT technology with reduced complexity and production costs, features that are highly anticipated in distributed diagnostics, monitoring, safety, and security applications.


Competition and cooperation among receptor tyrosine phosphatases control motoneuron growth cone guidance in Drosophila.
The neural receptor tyrosine phosphatases DPTP69D, DPTP99A and DLAR are involved in motor axon guidance in the Drosophila embryo. Here we analyze the requirements for these three phosphatases in growth cone guidance decisions along the ISN and SNb motor pathways. Any one of the three suffices for the progression of ISN pioneer growth cones beyond their first intermediate target in the dorsal muscle field. DLAR or DPTP69D can facilitate outgrowth beyond a second intermediate target, and DLAR is uniquely required for formation of a normal terminal arbor. A different pattern of partial redundancy among the three phosphatases is observed for the SNb pathway. Any one of the three suffices to allow SNb axons to leave the common ISN pathway at the exit junction. When DLAR is not expressed, however, SNb axons sometimes bypass their ventrolateral muscle targets after leaving the common pathway, instead growing out as a separate bundle adjacent to the ISN. This abnormal guidance decision can be completely suppressed by also removing DPTP99A, suggesting that DLAR turns off or counteracts a DPTP99A signal that favors the bypass axon trajectory. Our results show that the relationships among the tyrosine phosphatases are complex and dependent on cellular context. At growth cone choice points along one nerve, two phosphatases cooperate, while along another nerve these same phosphatases can act in opposition to one another.


Mitochondrial Respiration in Insulin-Producing β-Cells: General Characteristics and Adaptive Effects of Hypoxia.
To provide novel insights on mitochondrial respiration in β-cells and the adaptive effects of hypoxia. Insulin-producing INS-1 832/13 cells were exposed to 18 hours of hypoxia followed by 20-22 hours re-oxygenation. Mitochondrial respiration was measured by high-resolution respirometry in both intact and permeabilized cells, in the latter after establishing three functional substrate-uncoupler-inhibitor titration (SUIT) protocols. Concomitant measurements included proteins of mitochondrial complexes (Western blotting), ATP and insulin secretion. Intact cells exhibited a high degree of intrinsic uncoupling, comprising about 50% of oxygen consumption in the basal respiratory state. Hypoxia followed by re-oxygenation increased maximal overall respiration. Exploratory experiments in peremabilized cells could not show induction of respiration by malate or pyruvate as reducing substrates, thus glutamate and succinate were used as mitochondrial substrates in SUIT protocols. Permeabilized cells displayed a high capacity for oxidative phosphorylation for both complex I- and II-linked substrates in relation to maximum capacity of electron transfer. Previous hypoxia decreased phosphorylation control of complex I-linked respiration, but not in complex II-linked respiration. Coupling control ratios showed increased coupling efficiency for both complex I- and II-linked substrates in hypoxia-exposed cells. Respiratory rates overall were increased. Also previous hypoxia increased proteins of mitochondrial complexes I and II (Western blotting) in INS-1 cells as well as in rat and human islets. Mitochondrial effects were accompanied by unchanged levels of ATP, increased basal and preserved glucose-induced insulin secretion. Exposure of INS-1 832/13 cells to hypoxia, followed by a re-oxygenation period increases substrate-stimulated respiratory capacity and coupling efficiency. Such effects are accompanied by up-regulation of mitochondrial complexes also in pancreatic islets, highlighting adaptive capacities of possible importance in an islet transplantation setting. Results also indicate idiosyncrasies of β-cells that do not respire in response to a standard inclusion of malate in SUIT protocols.


Quantifying the availability and the stability of trace cationic elements in fly ash.
For adsorption-desorption controlled leaching processes, the total leachable mass and the adsorption constant are parameters representing the availability and the stability of trace elements in solid media. With these parameters, one can predict the leaching behavior of trace elements from solids under various pH and solid-to-liquid ratio conditions. An approach was developed in this paper to determine these parameters for model elements Cu(II), Cd(II), and Ni(II) in fly ash. This approach consists of a batch equilibrium titration, a batch equilibrium leaching with and without target element addition, and mathematical modeling. Results indicated that the adsorption constant of a trace element can be determined by modeling the adsorption ratio of the added element to the system as a function of pH. Results also indicated that the trace element originally present in fly ash had similar adsorption-desorption behavior as that added externally. By modeling the batch leaching data with and without external element addition, the total leachable mass and adsorption constant of the target element can be determined simultaneously. The total leachable mass is in agreement with experimental data from 50mM EDTA extraction.


Experimental cerebral vasospasm arterial wall mechanics and connective tissue composition.
The elastic properties of the basilar artery were studied in control and treated dogs in which 3 ml of blood was injected intracisternally. Vascular specimens were resected transclivally as cylindrical segments and their external diameters were measured in vitro in the pressure range from 0 mm Hg to 250 mm Hg in the active condition of smooth muscle in Krebs-Ringer solution and in the passive condition in saline solution. The development of cerebral vasospasm was confirmed comparing the diameter difference between these two conditions. The experimental data indicated that vasospasm was most prominent on the 7th day after the treatment of blood injection. In the passive condition no significant dimensional change (i.e. radius and wall thickness) was observed between the control and the treated arteries at various pressure levels. These results imply that the luminal narrowing under vasospasm is not attributable to an irreversible organic change in the wall but to the constriction of vascular smooth muscle. The treated arteries are more distensible and have lower elastic moduli than the control arteries, possibly due to a change in the content of their connective tissues. These changes of the passive elastic properties of arterial walls after blood injection might be one of the factors affecting the development of cerebral vasospasm.


Eating problems and overlap with ADHD and autism spectrum disorders in a nationwide twin study of 9- and 12-year-old children.
AIM. To establish the prevalence of restrictive eating problems, the overlap and association with attention-deficit/hyperactivity disorder (ADHD), and autism spectrum disorders (ASD) and to estimate the heritability of eating problems in a general population sample of twins aged 9 and 12. METHODS. Parents of all Swedish 9- and 12-year-old twin pairs born between 1993 and 1998 (n = 12,366) were interviewed regarding symptoms of ADHD, ASD, and eating problems (EAT-P). Intraclass correlations and structural equation modelling were used for evaluating the influence of genetic and environmental factors. Cross-twin, cross-trait correlations were used to indicate a possible overlap between conditions. RESULTS. The prevalence of eating problems was 0.6% in the study population and was significantly higher in children with ADHD and/or ASD. Among children with eating problems, 40% were screened positive for ADHD and/or ASD. Social interaction problems were strongly associated with EAT-P in girls, and impulsivity and activity problems with EAT-P in boys. The cross-twin, cross-trait correlations suggested low correlations between EAT-P and ADHD or EAT-P and ASD. Genetic effects accounted for 44% of the variation in liability for eating problems. CONCLUSIONS. In the group with eating problems, there was a clear overrepresentation of individuals with ADHD and/or ASD symptoms.


Human induced pluripotent stem cell models for the study and treatment of Duchenne and Becker muscular dystrophies.
Duchenne and Becker muscular dystrophies are the most common muscle diseases and are both currently incurable. They are caused by mutations in the dystrophin gene, which lead to the absence or reduction/truncation of the encoded protein, with progressive muscle degeneration that clinically manifests in muscle weakness, cardiac and respiratory involvement and early death. The limits of animal models to exactly reproduce human muscle disease and to predict clinically relevant treatment effects has prompted the development of more accurate in vitro skeletal muscle models. However, the challenge of effectively obtaining mature skeletal muscle cells or satellite stem cells as primary cultures has hampered the development of in vitro models. Here, we discuss the recently developed technologies that enable the differentiation of skeletal muscle from human induced pluripotent stem cells (iPSCs) of Duchenne and Becker patients. These systems recapitulate key disease features including inflammation and scarce regenerative myogenic capacity that are partially rescued by genetic and pharmacological therapies and can provide a useful platform to study and realize future therapeutic treatments. Implementation of this model also takes advantage of the developing genome editing field, which is a promising approach not only for correcting dystrophin, but also for modulating the underlying mechanisms of skeletal muscle development, regeneration and disease. These data prove the possibility of creating an accurate Duchenne and Becker in vitro model starting from iPSCs, to be used for pathogenetic studies and for drug screening to identify strategies capable of stopping or reversing muscular dystrophinopathies and other muscle diseases.


Diverse endogenous antigens for mouse NKT cells: self-antigens that are not glycosphingolipids.
NKT cells with an invariant Ag receptor (iNKT cells) represent a highly conserved and unique subset of T lymphocytes having properties of innate and adaptive immune cells. They have been reported to regulate a variety of immune responses, including the response to cancers and the development of autoimmunity. The development and activation of iNKT cells is dependent on self-Ags presented by the CD1d Ag-presenting molecule. It is widely believed that these self-Ags are glycosphingolipids (GSLs), molecules that contain ceramide as the lipid backbone. In this study, we used a variety of methods to show that mammalian Ags for mouse iNKT cells need not be GSLs, including the use of cell lines deficient in GSL biosynthesis and an inhibitor of GSL biosynthesis. Presentation of these Ags required the expression of CD1d molecules that could traffic to late endosomes, the site where self-Ag is acquired. Extracts of APCs contain a self-Ag that could stimulate iNKT cells when added to plates coated with soluble, rCD1d molecules. The Ag(s) in these extracts are resistant to sphingolipid-specific hydrolase digestion, consistent with the results using live APCs. Lyosphosphatidylcholine, a potential self-Ag that activated human iNKT cell lines, did not activate mouse iNKT cell hybridomas. Our data indicate that there may be more than one type of self-Ag for iNKT cells, that the self-Ags comparing mouse and human may not be conserved, and that the search to identify these molecules should not be confined to GSLs.


Quick change versus double pump while changing the infusion of inotropes: an experimental study.
Quick change (QC) and double pumping (DP) are common methods of substituting the infusion of inotropes given through intravenous pump. The aim of the study was to compare two methods in respect with the variation in mean arterial pressure (MAP). The hypothesis was that the DP method could be the most effective in achieving haemodynamic stability. The study is a randomized research in an open randomized clinical trial. The study took place at the Paediatric Intensive Care Unit of Padua Hospital. It considered patients of 0-36 months, not premature, treated with inotropic infusion with monitoring of blood pressure. The research obtained the approval of the Hospital Research Ethics committee and parents signed informed consent. Comparison of the two groups made use of the Wilcoxon test for the continuous variables and the Fisher's exact test for the comparison of frequencies, at significance value of 5%. The data were registered in an Excel spreadsheet and analysed with SAS. The sample comprised 30 patients of age between 1 and 27 months, of whom 13 (43%) were male. They were all affected by cardiac, respiratory or infective pathology, all of them intubated and on artificial respiratory support, sedated and infused with dopamine. The characteristics of the patients of the two groups did not differ significantly. The percentage variation of the baseline value of MAP after 30 min from starting the treatment between the two methods was not statistically significant (p = 0.85). The 95% confidence interval for the difference in the percentage variation of MAP between the two groups was (-3.1, +3.7). From a clinical perspective, the methods are to be considered equivalent. The study was conducted on a limited sample; no statistically significant differences were detected; QC is the quickest and more cost-effective method.


Contribution of hand and foot force to take-off velocity for the kick-start in competitive swimming.
This study examines the hand and foot reaction force recorded independently while performing the kick-start technique. Eleven male competitive swimmers performed three trials for the kick-start with maximum effort. Three force platforms (main block, backplate and handgrip) were used to measure reaction forces during starting motion. Force impulses from the hands, front foot and rearfoot were calculated via time integration. During the kick-start, the vertical impulse from the front foot was significantly higher than that from the rearfoot and the horizontal impulse from the rearfoot was significantly higher than that from the front foot. The force impulse from the front foot was dominant for generating vertical take-off velocity and the force impulse from the rearfoot was dominant for horizontal take-off velocity. The kick-start's shorter block time in comparison to prior measurements of the grab start was explained by the development of horizontal reaction force from the hands and the rearfoot at the beginning of the starting motion.


Performance of Plusoptix A09 Photo Screener in Refractive Error Screening in School Children Aged between 5 and 15 Years in the Southern Part of India.
To evaluate the performance of Plusoptix A09 in detecting ametropia, warranted against frequently-used technique of retinoscopy in children attending school (5-15 years) and its probability as a screening tool. This study was the subset of a larger epidemiological study visual acuity refractive error squint conducted in schools to determine the prevalence of ocular morbidity among the 5-15 years' school children population. Every 7th student in the class (each school had mean value of 100 students) was randomly selected for this study after ascertaining their eligibility as per the inclusion criteria. A cohort of a total of 150 children within the age group of 5-15 (mean, 10.21 ± 2.83) years were recruited from 11 schools of Udupi district. Students with best corrected visual acuity of 20/20, refractive error within ±5.00 diopter (D), without any eccentric fixation, and no history of ocular pathology or seizures were recruited. Refractive error was tested by Plusoptix photorefractor followed by non-cycloplegic and cycloplegic retinoscopic techniques. The examiners performing these tests were masked and unware of the findings. Bland Altman plotted the agreement between the techniques, followed by the receiver operating characteristic curve (ROC), and sensitivity of Plusoptix. One-way analysis of variance calculated statistical differences among Plusoptix, objective retinoscopy, and cycloplegic retinoscopy for mean spherical value (1.12 ± 1.16 D, 0.65 ± 0.69 D, and 0.8 ± 0.82 D), cylindrical value (-0.83 D ± 1.27, -0.32 D ± 0.86, and -0.34 D ± -0.93), and spherical equivalent value (0.71 D ± 1.06, 0.45 D ± 0.7, and 0.61 D ± 0.81), with P = 0.0001, 0.0001, and 0.097, respectively. Bland Altman plots showed good agreement for spherical equivalent values of Plusoptix and objective retinoscopy. However, the area under the ROC curve (0.386) suggests that lower diagnostic ability of this device in this age group population in comparison to retinoscopy (0.575) with the sensitivity and specificity of Plusoptix was 69.2% and 84.8%. This study fails to report ideal sensitivity mandated for a screening tool, although good specificity and agreement are observed. Along with retinoscopy, this tool will be effective in screening a children's population aged between the age group of 5 and 15 years.


Anomalous thickness-dependence of photocurrent explained for state-of-the-art planar nano-heterojunction organic solar cells.
Due to their simple geometry and design, planar heterojunction (PHJ) solar cells have advantages both as potential photovoltaics with more efficient charge extraction than their bulk heterojunction (BHJ) counterparts, and as idealized interfaces to study basic device operation. The main reason for creating BHJs was the limited exciton diffusion length in the active materials of the PHJ: if an exciton is generated at a distance greater than its diffusion length from the hetero-interface of the PHJ, it would be very unlikely to be able to contribute to the photocurrent. Based on this argument one expects a maximum in the photocurrent of PHJs for a thickness of the active layer equal to the exciton diffusion length (~10 nm). However, in two recently developed PHJs that have appeared in the literature, a maximum photocurrent is observed for 60-65 nm of poly(3-hexylthiophene) (P3HT). In this work, we explore this anomaly by combining both an optical T-matrix and a kinetic Monte Carlo simulation that tracks the exciton behavior in the PHJs. The two systems considered are a P3HT/single walled carbon nanotube (SWNT) device, and a P3HT/phenyl-C61-butyric acid methyl ester (PCBM) device. The model demonstrates how a bulk exciton sink can explain the shifted maximum in the P3HT/SWNT case, whereas in the P3HT/PCBM case the maximum is mainly determined by PCBM molecules interdiffusing in the P3HT upon annealing. Based upon the results of this model it will be possible to more intelligently design nanostructured photovoltaics and optimize them toward higher efficiencies.


Predictors of Recurrent Stroke in Patients with Ischemic Stroke: Comparison Study between Transesophageal Echocardiography and Cardiac CT.
To investigate cardiac computed tomographic (CT) findings predictive of recurrent stroke in patients with ischemic stroke and determine the incremental risk stratification benefit of cardiac CT findings compared with transesophageal echocardiography (TEE) findings in patients with ischemic stroke. This single-center prospective study protocol was approved by the institutional review boards, and written informed consent was obtained from all patients. Among 548 consecutive patients, 374 patients with ischemic stroke (254 men and 120 women, with a mean age of 63.1 years) who underwent TEE and cardiac CT were prospectively enrolled in this study. TEE and cardiac CT images were assessed for cardioembolic sources, including thrombus, tumor, spontaneous echo contrast, valvular vegetation, atrial septal aneurysm, patent foramen ovale, and aortic plaque. The primary end point was stroke recurrence. Prognostic factors were assessed with Cox univariate and multivariate analysis. The integrated area under the receiver operating characteristic curve was calculated to compare the prognostic abilities of CT and TEE parameters. During a median follow-up period of 433 days, there were a total of 28 recurrent stroke events. The TEE parameter of plaque complexity (hazard ratio, 13.512; 95% confidence interval: 3.668, 49.778; P < .001) and CT parameter of plaque complexity (hazard ratio, 32.538; 95% confidence interval: 7.544, 140.347; P < .001) were predictors of recurrent stroke. The time-dependent receiver operating characteristic curve analysis demonstrated no significant differences in prediction of recurrent stroke between TEE and CT parameters (integrated area under the receiver operating characteristic curve, 0.812 vs 0.840, respectively). Complex aortic plaque evaluated with cardiac CT and TEE was associated with an increased risk of stroke recurrence in patients with ischemic stroke.


Interpreting hemoglobin and water concentration, oxygen saturation, and scattering measured in vivo by near-infrared breast tomography.
Near-infrared spectroscopic tomography was used to measure the properties of 24 mammographically normal breasts to quantify whole-breast absorption and scattering spectra and to evaluate which tissue composition characteristics can be determined from these spectra. The absorption spectrum of breast tissue allows quantification of (i) total hemoglobin concentration, (ii) hemoglobin oxygen saturation, and (iii) water concentration, whereas the scattering spectrum provides information about the size and number density of cellular components and structural matrix elements. These property data were tested for correlation to demographic information, including subject age, body mass index, breast size, and radiographic density. Total hemoglobin concentration correlated inversely to body mass index, likely because lower body mass indicates proportionately less fat and more glandular tissue, and glandular tissue contains greater vascularity, hence, more total hemoglobin. Optical scattering was correlated to breast diameter, subject age, and radiographic density. In the radiographic density, fatty breasts had low scattering power and extremely dense breasts had higher values. This observation is consistent with low attenuation of conventional x-rays with fat and higher attenuation in glandular tissues. Optically, fatty tissues have large scatterers leading to a low scattering power, whereas glandular or fibrous tissues have more cellular and collagen-based structures that lead to high scattering power. The study presents correlative data supporting the hypothesis that optical measurements of absorption and scattering can provide physiologically relevant information about breast tissue composition. These breast constituents vary significantly between individuals and can be altered because of changes in breast physiology or pathological state.


Cerebrovascular hemodynamics in arteriovenous malformation complicated by normal perfusion pressure breakthrough.
Catastrophic hyperemic states are known complications after the treatment of certain types of intracranial arteriovenous malformations (AVMs). A case is presented in which a large AVM was preoperatively embolized and later resected. There was clear intra- and postoperative evidence of edema and hemorrhage, which resulted in a fatal outcome. Regional cerebral blood flow (rCBF) data from this patient obtained with single photon emission computed tomography (SPECT) both before and after embolization were compared with data from four patients with similar size supratentorial AVMs treated and studied in a similar protocol who did not develop perfusion breakthrough. Pretreatment hemispheric rCBF was significantly reduced in this patient's ipsilateral hemisphere (50 ml/100 g/min) compared to the control group mean (83 +/- 9.5 ml/100 g/min). A similar relative depression was found in the contralateral hemisphere. After therapeutic embolization, the ipsilateral rCBF increased by 33 ml/100 g/min and the contralateral hemispheric rCBF increased by 30 ml/100 g/min; this embolization-induced increase in rCBF was significantly higher than in the control group. Acetazolamide, known to increase rCBF in normal tissue by 35 +/- 3%, resulted in a 56% augmentation of ipsilateral hemispheric flow before embolization in the reported patient vs. a 22 +/- 10% increase for the control group. Postembolization, this hyperresponsiveness to acetazolamide remained unchanged. It is possible that these hemodynamic derangements may indicate a dissociation between the vasoconstrictive and vasodilatory reactivity in chronically hypoperfused territories adjacent to AVMs such that pharmacological or metabolic stimuli may induce further vasodilation, but sudden redistribution of large volumes of flow will not promote protective vasoconstriction.


The location of the active-site histidine residue in the primary sequence of papain.
Papain that had been irreversibly inhibited with 1,3-dibromo[2-(14)C]acetone was reduced with sodium borohydride and carboxymethylated with iodoacetic acid. After digestion with trypsin and alpha-chymotrypsin the radioactive peptides were purified chromatographically. Their amino acid composition indicated that cysteine-25 and histidine-106 were cross-linked. Since cysteine-25 is known to be the active-site cysteine residue, histidine-106 must be the active-site histidine residue.


Effects of a combined physical training and nutrition intervention on physical performance and health-related quality of life in prefrail older women living in the community: a randomized controlled trial.
The purpose of this study was to examine whether a 12-week combined physical exercise training and nutritional intervention improves physical performance and enhances health-related quality of life (HRQOL) among prefrail elderly women living in the community. This was a randomized controlled trial in which participants were recruited and randomly assigned to the exercise and nutrition group (EN, n = 30), exercise only group (E, n = 28), and control group (C, n = 31). Group training classes were held at a research center in Itabashi Ward, Tokyo, Japan. Eighty-nine prefrail women aged 70 years or older. The EN group participated in an exercise training and nutritional program (cooking class) once a week, and the E group participated in the exercise training program only. Outcome measures that included physical performance (handgrip strength, balance, walking speed) and HRQOL (Medical Outcomes Study 36-Item Short Form Health Survey) were obtained at entry, the end of the 12-week intervention, and 6 months after completion of the intervention program. At the end of the 12-week intervention, significant improvements in the physical component summary score and 3 (role physical, bodily pain, role emotional) of the 8 domains of the Medical Outcomes Study 36-Item Short Form Health Survey were observed in the EN group. The E group exhibited a significantly increased handgrip strength at postintervention. The positive effects, however, were not maintained at 6-month follow-up, but were reduced. The combined physical exercise training and nutritional intervention program has beneficial effects on several domains of HRQOL and handgrip strength in prefrail elderly women living in the community. However, further studies are needed to examine approaches that facilitate maintenance of the improved outcomes by combined exercise training and nutritional intervention.


Resource footprints and their ecosystem consequences.
A meaningful environmental impact analysis should go beyond the accounting of pressures from resource use and actually assess how resource demand affects ecosystems. The various currently available footprints of nations report the environmental pressures e.g. water use or pollutant emissions, driven by consumption. However, there have been limited attempts to assess the environmental consequences of these pressures. Ultimately, consequences, not pressures, should guide environmental policymaking. The newly released LC-Impact method demonstrates progress on the path to providing this missing link. Here we present "ecosystem impact footprints" in terms of the consequences for biodiversity and assess the differences in impact footprint results from MRIO-based pressure footprints. The new perspective reveals major changes in the relative contribution of nations to global footprints. Wealthy countries have high pressure footprints in lower-income countries but their impact footprints often have their origin in higher-income countries. This shift in perspective provides a different insight on where to focus policy responses to preserve biodiversity.


Longitudinal study of human papillomavirus persistence and cervical intraepithelial neoplasia grade 2/3: critical role of duration of infection.
The natural history of human papillomavirus (HPV) infections in older women is critical for preventive strategies, including vaccination and screening intervals, but is poorly understood. In a 7-year population-based cohort study in Guanacaste, Costa Rica, we examined whether women's age and the duration of carcinogenic HPV infections influenced subsequent persistence of infection and risk of cervical intraepithelial neoplasia grade 2 (CIN 2) or worse disease. At enrollment, of the 9466 participants eligible for pelvic examination, 9175 were screened for cervical neoplasia using multiple methods; those with CIN 2 or worse disease were censored and treated. Participants at low risk of CIN 2 or worse (n = 6029) were rescreened at 5-7 years (passively followed), whereas higher-risk participants (n = 2115) and subsets of low-risk women (n = 540) and initially sexually inactive women (n = 410) were rescreened annually or semiannually (actively followed) for up to 7 years. HPV testing was done using a polymerase chain reaction-based method. We determined, by four age groups (18-25, 26-33, 34-41, and > or =42 years), the proportion of prevalent infections (found at baseline) and newly detected infections (first found during follow-up) that persisted at successive 1-year time points and calculated absolute risks of CIN 2 and CIN grade 3 (CIN 3) or worse during follow-up. P values are two-sided. Regardless of the woman's age, newly detected infections were associated with very low absolute risks of persistence, CIN 2, or worse disease. For newly detected infections, the rate of progression to CIN 2+ (or CIN 3+), after 3 years of follow-up, was not higher for women aged 34 years and older than for younger women. Moreover, rates of newly detected infections declined sharply with age (in the actively followed group, at ages 18-25, 26-33, 34-41, and > or =42 years, rates were 35.9%, 30.6%, 18.1%, and 13.5%, respectively; P < .001). Among prevalent infections, persistent infections among older women (> or =42 years) was higher than that among younger age groups or new infections at any age (P < .01 for comparison of eight groups). Most (66 of 85) CIN 2 or worse detected during follow-up was associated with prevalent infections. Only a small subset (25 of 1128) of prevalent infections persisted throughout follow-up without apparent CIN 2 or worse. The rate of new infections declines with age, and new infections typically do not progress to CIN 2 or worse disease in older women; thus, overall potential benefit of prophylactic vaccination or frequent HPV screening to prevent or detect new carcinogenic HPV infections at older ages is low.


The SOS-framework (Systems of Sedentary behaviours): an international transdisciplinary consensus framework for the study of determinants, research priorities and policy on sedentary behaviour across the life course: a DEDIPAC-study.
Ecological models are currently the most used approaches to classify and conceptualise determinants of sedentary behaviour, but these approaches are limited in their ability to capture the complexity of and interplay between determinants. The aim of the project described here was to develop a transdisciplinary dynamic framework, grounded in a system-based approach, for research on determinants of sedentary behaviour across the life span and intervention and policy planning and evaluation. A comprehensive concept mapping approach was used to develop the Systems Of Sedentary behaviours (SOS) framework, involving four main phases: (1) preparation, (2) generation of statements, (3) structuring (sorting and ranking), and (4) analysis and interpretation. The first two phases were undertaken between December 2013 and February 2015 by the DEDIPAC KH team (DEterminants of DIet and Physical Activity Knowledge Hub). The last two phases were completed during a two-day consensus meeting in June 2015. During the first phase, 550 factors regarding sedentary behaviour were listed across three age groups (i.e., youths, adults and older adults), which were reduced to a final list of 190 life course factors in phase 2 used during the consensus meeting. In total, 69 international delegates, seven invited experts and one concept mapping consultant attended the consensus meeting. The final framework obtained during that meeting consisted of six clusters of determinants: Physical Health and Wellbeing (71% consensus), Social and Cultural Context (59% consensus), Built and Natural Environment (65% consensus), Psychology and Behaviour (80% consensus), Politics and Economics (78% consensus), and Institutional and Home Settings (78% consensus). Conducting studies on Institutional Settings was ranked as the first research priority. The view that this framework captures a system-based map of determinants of sedentary behaviour was expressed by 89% of the participants. Through an international transdisciplinary consensus process, the SOS framework was developed for the determinants of sedentary behaviour through the life course. Investigating the influence of Institutional and Home Settings was deemed to be the most important area of research to focus on at present and potentially the most modifiable. The SOS framework can be used as an important tool to prioritise future research and to develop policies to reduce sedentary time.


Minimally invasive oesophagectomy: current status and future direction.
Oesophagectomy is one of the most challenging surgeries. Potential for morbidity and mortality is high. Minimally invasive techniques have been introduced in an attempt to reduce postoperative complications and recovery times. Debate continues over whether these techniques are beneficial to morbidity and whether oncological resection is compromised. This review article will analyse the different techniques employed in minimally invasive oesophagectomy (MIO) and critically evaluate commonly reported outcome measures from the available literature. Medline, Embase, Science Citation Index, Current Contents, and PubMed databases were used to search English language articles published on MIO. Thirty-one articles underwent thorough analysis and the data were tabulated where appropriate. To date, only level III evidence exists. Where appropriate, comparisons are made with a meta-analysis on open oesophagectomy. Positive aspects of MIO include at least comparable postoperative recovery data and oncological resection measures to open surgery. Intensive care unit requirements are lower, as is duration of inpatient stay. Respiratory morbidity varies. Negative aspects include increased technical skill of the surgeon and increased equipment requirements, increased operative time and limitation with respect to local advancement of cancer. With increasing individual experience, improvements in outcome measures and the amenability of this approach to increasing neoplastic advancement has been shown. MIO has outcome measures at least as comparable to open oesophagectomy in the setting of benign and nonlocally advanced cancer. Transthoracic oesophagectomy provides superior exposure to the thoracic oesophagus compared to the transhiatal approach and is currently preferred. No multicentre randomised controlled trials exist or are likely to come into fruition. As with all surgery, careful patient selection is required for optimal results from MIO.


Coffee consumption and risk of stroke: a dose-response meta-analysis of prospective studies.
Coffee consumption has been inconsistently associated with risk of stroke. The authors conducted a meta-analysis of prospective studies to quantitatively assess the association between coffee consumption and stroke risk. Pertinent studies were identified by searching PubMed and Embase from January 1966 through May 2011 and by reviewing the reference lists of retrieved articles. Prospective studies in which investigators reported relative risks of stroke for 3 or more categories of coffee consumption were eligible. Results from individual studies were pooled using a random-effects model. Eleven prospective studies, with 10,003 cases of stroke and 479,689 participants, met the inclusion criteria. There was some evidence of a nonlinear association between coffee consumption and risk of stroke (P for nonlinearity = 0.005). Compared with no coffee consumption, the relative risks of stroke were 0.86 (95% confidence interval (95% CI): 0.78, 0.94) for 2 cups of coffee per day, 0.83 (95% CI: 0.74, 0.92) for 3-4 cups/day, 0.87 (95% CI: 0.77, 0.97) for 6 cups/day, and 0.93 (95% CI: 0.79, 1.08) for 8 cups/day. There was marginal between-study heterogeneity among study-specific trends (I₂ = 12% and I₂ = 20% for the first and second spline transformations, respectively). Findings from this meta-analysis indicate that moderate coffee consumption may be weakly inversely associated with risk of stroke.


The Effect of Continuous Enteral Nutrition on Nutrition Indices, Compared to the Intermittent and Combination Enteral Nutrition in Traumatic Brain Injury Patients.
Nutrition support is one of the most common care, which is undertaken for patients who suffered from Traumatic Brain Injury (TBI) and are admitted in intensive care units. Literature indicates some controversies regarding the appropriate method of nutrition support in these patients. This study was conducted for determining the effect of continuous enteral nutrition on nutrition indices, compared to the intermittent enteral and combination nutrition in TBI patients. In a randomized clinical trial, 60 TBI patients who were admitted to critical care units of Taleghani Hospital of Kermanshah-Iran in 2010 recruited to the study. The samples were allocated to three groups of continuous enteral nutrition, intermittent enteral nutrition and combination nutrition supports by random sampling. The tool was a researcher-made checklist. The three methods of nutrition support were performed to the participants, then nutrition indices of patients were measured before and during three weeks. Data were analysed using SPSS software, descriptive, and inferential statistics. The mean of received energy in the combination group (53.1± 18.3%) was higher than continuous (38.5±19.7%) and intermittent (32.2±14.7%) groups, significantly (p<0.001). The received protein was also greater in combination method (67.7±16.9%) than continuous (31.8±15.1%) and intermittent groups (17.2±10.1%), (p=0.001). The mean of nitrogen balance was improved in continuous method from -4.7± -1.6 to 7.2±5.2, (p<0.001) significantly. In this study, received energy of patients was not enough by three methods. However, the continuous method, having a positive effect on nitrogen balance, reducing hypercatabolism and maintaining the total body protein, was preferred to brain injury patients compared with intermittent enteral and parenteral methods that demand more studies.


Epidemiology of incident heart failure in a contemporary elderly cohort: the health, aging, and body composition study.
The race- and sex-specific epidemiology of incident heart failure (HF) among a contemporary elderly cohort are not well described. We studied 2934 participants without HF enrolled in the Health, Aging, and Body Composition Study (mean [SD] age, 73.6 [2.9] years; 47.9% men; 58.6% white; and 41.4% black) and assessed the incidence of HF, population-attributable risk (PAR) of independent risk factors for HF, and outcomes of incident HF. During a median follow-up of 7.1 years, 258 participants (8.8%) developed HF (13.6 cases per 1000 person-years; 95% confidence interval, 12.1-15.4). Men and black participants were more likely to develop HF. No significant sex-based differences were observed in risk factors. Coronary heart disease (PAR, 23.9% for white participants and 29.5% for black participants) and uncontrolled blood pressure (PAR, 21.3% for white participants and 30.1% for black participants) carried the highest PAR in both races. Among black participants, 6 of 8 risk factors assessed (smoking, increased heart rate, coronary heart disease, left ventricular hypertrophy, uncontrolled blood pressure, and reduced glomerular filtration rate) had more than 5% higher PAR compared with that among white participants, leading to a higher overall proportion of HF attributable to modifiable risk factors in black participants vs white participants (67.8% vs 48.9%). Participants who developed HF had higher annual mortality (18.0% vs 2.7%). No racial difference in survival after HF was noted; however, rehospitalization rates were higher among black participants (62.1 vs 30.3 hospitalizations per 100 person-years, P < .001). Incident HF is common in older persons; a large proportion of HF risk is attributed to modifiable risk factors. Racial differences in risk factors for HF and in hospitalization rates after HF need to be considered in prevention and treatment efforts.


Elemental analysis mirrors epidermal differentiation.
Using a scanning nuclear microprobe, the distribution of elements and trace elements of skin cross sections of normal skin, non-lesional psoriatic skin and in dry atopic skin have been mapped. In non-lesional psoriatic skin and in dry atopic skin the epidermal Ca-gradient is higher than that of normal skin. In addition, abnormally high Fe and Zn levels were recorded in the stratum granulosum and corneum regions in the pathological skin. It is suggested that these findings correlate to an increased cell turnover in the basal cell layer of the psoriatic and atopic skins. The ratio of Ca/Zn in stratum corneum of paralesional psoriatic skin is approximately 8:1 compared to 12: 1 in normal skin and 15: 1 in atopic skin. This suggests that the differentiation process in paralesional psoriatic skin may actually be an example of disturbed programmed cell death.


Resting Energy Expenditure Measured by Indirect Calorimetry in Infants and Young Children with Chronic Lung Disease.
To determine resting energy expenditure (REE) by indirect calorimetry and to compare measured resting energy expenditure (mREE) by indirect calorimetry with prediction equations (pREE). Infants and young children with chronic lung diseases from King Chulalongkorn Memorial Hospital were enrolled and assessed for nutritional status and severity of chronic lung diseases. For mREE, indirect calorimetry was performed by custom-made airtight canopy with O2 and CO2 sensors, with the patients were in a resting state. Prediction equations were Food and Agriculture/World Health Organization/United Nations University (FAO/WHO/UNU), Schofield-Weight, Schofield-Weight/Height, Harris Benedict, and Harris Benedict-Infant equations. Agreement between mREE and pREE was assessed by Bland-Altman method. Eighteen patients (median age 6 months, range 1 to 26 months) were recruited. Sixteen children had weight for age Z-score below -2 SD. Median weight for age Z-score, length for age Z-score and weight for length Z-score were -3.0, -3.1, and -1.9, respectively. Median mREE was 53.8 kcal/kg/day (interquartile range 47.5 to 72.6 kcal/kg/day). The Schofield-Weight/Height equation showed the lowest mean of difference at 0.94 kcal/kg/day with 95% confidence interval for the bias -44.4 to 46.3 kcal/kg/day. To ensure optimal nutritional support, REE should be measured by indirect calorimetry in pediatric patients with chronic lung diseases. Based on our finding, the Schofield-Weight/Height equation was the most accurate equation for predicting REE in this group of patients.


A pilot study of core body temperatures in healthcare workers wearing personal protective equipment in a high-level isolation unit.
Personal protective equipment used by healthcare workers to mitigate disease transmission risks while caring for patients with high-consequence infectious diseases can impair normal body cooling mechanisms and exacerbate physiological strain. Symptoms of heat strain (e.g., cognitive impairment, confusion, muscle cramping) are especially harmful in the high-risk environment of high-consequence infectious disease care. In this pilot study, the core body temperatures of healthcare workers were assessed using an ingestible, wireless-transmission thermometer while performing patient care tasks common to a high-level isolation unit setting in powered air purifying respirator (PAPR)-level. The objective was to determine the potential for occupational health hazard due to heat stress in an environmentally controlled unit. Maximum core temperatures of the six participants ranged from 37.4 °C (99.3 °F) to 39.9 °C (103.8°F) during the 4-hr shift; core temperatures of half (n = 3) of the participants exceeded 38.5 °C (101.3 °F), the upper core temperature limit. Future investigations are needed to identify other heat stress risks both in and outside of controlled units. The ongoing COVID-19 pandemic offers unique opportunities for field-based research on risks of heat stress related to personal protective equipment in healthcare workers that can lead to both short- and long-term innovations in this field.


Three-dimensional imaging of direct-written photonic structures.
Third-harmonic generation microscopy has been used to analyze the morphology of photonic structures created using the femtosecond laser direct-write technique. Three-dimensional waveguide arrays and waveguide-Bragg gratings written in fused-silica and doped phosphate glass were investigated. A sensorless adaptive-optical system was used to correct the optical aberrations occurring in the sample and microscope system, which had a lateral resolution of less than 500 nm. This nondestructive testing method creates volume reconstructions of photonic devices and reveals details invisible to other linear microscopy and index profilometry techniques.


Bone marrow dendritic cells internalize live RF-81 bovine rotavirus and rotavirus-like particles (RF 2/6-GFP-VLP and RF 8*2/6/7-VLP) but are only activated by live bovine rotavirus.
Dendritic cells (DC) represent the link between innate and adaptive immunity. They are classified as antigen-presenting cells (APC) and can initiate and modulate the immune response. To investigate the interaction with DCs, live RF-81 bovine rotavirus strain (RFV) and rotavirus-like particles (rota-VLP), RF 2/6-GFP-VLP and rota RF 8*2/6/7-VLP, were added in vitro to murine bone marrow-derived DCs (bmDCs). Live RFV, RF 2/6-GFP-VLP and RF 8*2/6/7-VLP all bound to bmDC and were internalized but only live RFV stimulated phenotypic maturation of the bmDCs as shown by the upregulation of the co-stimulatory molecule CD86. Even though bmDCs internalized RF 2/6-GFP-VLP and RF 8*2/6/7-VLP as efficiently as live RFV, these rota-VLP were not able to activate the cells. Supernatants derived from bmDC cultures treated with live RFV, RF 2/6-GFP-VLP or RF 8*2/6/7-VLP were examined for TNF-alpha production. At 6, 18 and 24 h post-infection, TNF-alpha concentrations were significantly increased in cultures treated with live RFV and rota-VLP compared with untreated cultures. In conclusion, this study showed that live RF-81 bovine rotavirus strain was internalized and induced bmDCs activation, whereas both RF 2/6-GFP-VLP and RF 8*2/6/7-VLP were internalized by bmDCs without triggering their activation.


Radioguided parathyroidectomy for recurrent hyperparathyroidism caused by forearm graft hyperplasia.
One of the surgical options for symptomatic secondary hyperparathyroidism is a total parathyroidectomy with forearm implantation. Recurrence can occur and is most likely caused by hyperplasia of the small fragments of parathyroid tissue implanted in the forearm muscle. Forearm graft hyperplasia can be detected using Tc-99m sestamibi scanning of the forearm, which can show abnormal enhancement at the former graft site. In this report, we present the case of a 49-year-old gentleman with recurrent hyperparathyroidism caused by hyperplasia of forearm graft fragments. Unfortunately, no sutures or clips were placed at his initial surgery to identify the location of the parathyroid tissue in the forearm. Thus, we describe the first reported use of radioguided techniques using Tc-99m sestamibi injection and intraoperative gamma probe to localize parathyroid fragments in the forearm muscle. During our initial exploration, we found that injection of the tracer in the operative arm leads to prohibitively high levels of background activity. During a second exploration, the tracer was injected in the lower extremity, minimizing the background in the forearm and allowing the gamma probe to clearly identify two areas of abnormal parathyroid tissue. The intraoperative radioprobe allowed quick identification and removal of the abnormal parathyroid tissue in a case that was made particularly challenging by the absence of marking sutures.


Lameness Prevalence and Risk Factors in Large Dairy Farms in Upstate New York. Model Development for the Prediction of Claw Horn Disruption Lesions.
The main objectives of this prospective cohort study were a) to describe lameness prevalence at drying off in large high producing New York State herds based on visual locomotion score (VLS) and identify potential cow and herd level risk factors, and b) to develop a model that will predict the probability of a cow developing claw horn disruption lesions (CHDL) in the subsequent lactation using cow level variables collected at drying off and/or available from farm management software. Data were collected from 23 large commercial dairy farms located in upstate New York. A total of 7,687 dry cows, that were less than 265 days in gestation, were enrolled in the study. Farms were visited between May 2012 and March 2013, and cows were assessed for body condition score (BCS) and VLS. Data on the CHDL events recorded by the farm employees were extracted from the Dairy-Comp 305 database, as well as information regarding the studied cows' health events, milk production, and reproductive records throughout the previous and subsequent lactation period. Univariable analyses and mixed multivariable logistic regression models were used to analyse the data at the cow level. The overall average prevalence of lameness (VLS > 2) at drying off was 14%. Lactation group, previous CHDL, mature equivalent 305-d milk yield (ME305), season, BCS at drying off and sire PTA for strength were all significantly associated with lameness at the drying off (cow-level). Lameness at drying off was associated with CHDL incidence in the subsequent lactation, as well as lactation group, previous CHDL and ME305. These risk factors for CHDL in the subsequent lactation were included in our predictive model and adjusted predicted probabilities for CHDL were calculated for all studied cows. ROC analysis identified an optimum cut-off point for these probabilities and using this cut-off point we could predict CHDL incidence in the subsequent lactation with an overall specificity of 75% and sensitivity of 59%. Using this approach, we would have detected 33% of the studied population as being at risk, eventually identifying 59% of future CHDL cases. Our predictive model could help dairy producers focusing their efforts on CHDL reduction by implementing aggressive preventive measures for high risk cows.


Interprofessional Education and Collaboration in Healthcare: An Exploratory Study of the Perspectives of Medical Students in the United States.
Qualified and competent healthcare professionals working in a collaborative team environment is a prerequisite for high quality patient care. In order to be successful in the healthcare working environment, medical students need to be exposed to interprofessional learning early in their education. A single stage online survey was administered to medical students to evaluate their attitudes and perceptions of interprofessional education (IPE) and whether prior exposure to IPE increased their appreciation for interprofessional collaboration. The results suggest that irrespective of prior exposure to IPE, medical students appreciated the importance of interprofessional education and collaboration. Medical students showed a strong interest in attending interprofessional courses in other disciplines. Time constraints, scheduling conflicts, and communication emerged as barriers to IPE. Medical students embraced IPE and welcomed the opportunity to learn with other disciplines. Clinical case studies and simulations were identified as potential methods to integrate with other healthcare disciplines. The positive attitude and perceptions of the medical students toward interprofessional education and collaboration warrants the inclusion of related courses in medical curricula, as this may further increase students' potentials in becoming effective healthcare providers.


THE BICARBONATE RESERVE AND THE DISSOCIATION CURVE OF OXYHEMOGLOBIN IN FEBRILE CONDITIONS.
From Fig. 1 it may be seen that the effect of elevated temperature during the pyrexial period upon 1/K and therefore on the dissociation curve of oxyhemoglobin was, on the average, greater than would have been expected from experiments on normal blood in vitro, and greater than would be expected in view of the alkalosis occurring See PDF for Structure during fever. Temperature rise, and excess hydroxyl ion acting in vitro in the opposite directions, seemed to indicate a more stable state of affairs than was found. Apparently other factors have come into play, as, for example, alterations in the proportions and concentrations of the various electrolytes. In pneumonia, for instance, there is a retention of chloride during the febrile period with excessive loss of phosphates. The variations were not due to variations in the hemoglobin molecule itself since from the work of Adair, Barcroft, and Bock (18) hemoglobin must apparently be reckoned as having identical properties in normal individuals of the same species. If Barcroft's (19) hypothesis be right, namely that the C(H) within the corpuscle is higher than that of the plasma, the observed variations of 1/K may not be so surprising. In view of the fact that the hemoglobin inside the corpuscle is enclosed within a semipermeable membrane, the possibility arises of the setting up of membrane equilibria which will protect the respiratory pigment from excessive changes of reaction that may occur in the plasma, and thus the optimum conditions for the carriage of oxygen to the tissues may be maintained. Krogh and Leitch (10) in 1919 also drew attention to the protected situation of hemoglobin inside the corpuscle. In Case 6 it seems as if the alkalosis consequent on the febrile state had gained the upper hand and had extinguished the normal temperature reaction. This is rather confirmed by the fact that clinically the case showed one of the earlier signs of an alkalosis; namely, twitching of the facial muscles. Case 10, who had been on salicylate, also showed an analogous effect, when 6 days after the first observation the temperature shift was practically nil. The relationship between pH, 1/K, and the febrile temperature still awaits investigation. The extent of the shift of the dissociation curve was not by any means uniform; in neither Fig. 1 nor Fig. 2 is the highest value of 1/K at the highest temperature recorded. Fig. 2 shows the effect of temperature rise upon 1/K after cessation of the pyrexia; the effect is not so marked. Some cases, however, showed a variation in excess of the normal as if there was not yet complete return to normal. See PDF for Structure Biologically these changes are of importance in that this shifting of the dissociation curve to the right in fever means that there is more oxygen available for the tissues than normally, more especially at higher pressures. The tension of unloading is raised. This, in addition to the accelerated circulation and the probable increased velocity o[ reaction, means that even in a localized area of inflammation, if there is increased temperature, the tissues are placed in a better position for resisting infection as a result of their better oxygenation. That there is increased metabolism during fever has been conclusively shown by Du Bois (20) and others using large bed calorimeters. Du Bois has shown that the increase in metabolism obeys van't Hoff's law, increasing 13 per cent for each 1 degrees C. rise. This shifting of the curve then falls into line with these observations as an adaptive response to the febrile condition, and the febrile temperature, if not too great, would seem to be a purposive attempt to aid the combating of infection. This shifting of the curve probably explains Uyeno's (21) observation on the effect of increased temperature on the circulation in the cat; namely, increased coefficient of utilization, and increased fall in the saturation of the mixed venous blood. Turning now to Table II, we find that, if the CO(2) dissociation curve of Haldane (12) is accepted as normal, the bicarbonate reserve of five of the cases was above normal, of one normal, and of the rest below normal. Gastric secretion was not the cause of the varying curves, since the time of drawing the blood in all cases was during intestinal digestion. No observations having been made on the blood pH or the alveolar CO(2), we cannot be absolutely certain as to the actual reactions, more especially in the last cases; Case 6, however, was probably one showing a partially compensated CO(2) deficit in view of the absolute lowering of the total bicarbonate and evidence clinically of a tendency to alkalosis. Case 3, which had a lowered reserve, was probably similar. Koehler (22) gives a series of blood pH determinations in acute fevers in which ten out of twelve cases showed an uncompensated alkalosis when the temperature was 103 degrees F. (39.4 degrees C.) or over. Pemberton and Crouter (23) in a study on the response to the therapeutic application of external heat also observed a tendency for the reaction to shift to the alkaline side as shown by the alteration in the pH of the sweat. Hill and Flack (24) and Bazett and Haldane (25) observed that in thermal fever there was an excessive loss of CO(2) comparable to the effect of hyperpnea. These facts are of importance in view of the above results regarding the bicarbonate reserve. That there was a definite alkalosis in some of the cases is at least shown by the value of 1/K at 37.0 degrees C. during the pyrexial period in Cases 1, 2, and 7. The upper limits of 1/K at 37.0 degrees C. both during pyrexia and after were similar. Of other factors that might be considered, reference may be made to the work of Barbour and his associates (26-29), who showed that in hyperthermia and fever there is an alteration in the concentration of the blood. But the changes were hardly of such magnitude as to cause the variations above detailed.


Computerized tomography guided sacroplasty: a practical treatment for sacral insufficiency fracture: case report.
Small case series projecting widespread therapeutic implications. To promote sacroplasty as a feasible treatment for sacral insufficiency fractures. Osteoporosis, a major cause of vertebral and sacral insufficiency fractures, is an increasingly serious problem in the elderly population. Painful sacral fractures often cause patients to be immobile, and at increased risk for comorbidities and osteoporosis progression. Currently, there is no therapy available for the treatment of these fractures. Vertebroplasty has evolved as a standard of care for treating fractures as a result of malignant and nonmalignant spinal pathology. Sacroplasty represents a reasonable adaptation of this interventional technique. Computerized tomography (CT) guidance was used to monitor percutaneous polymethylmethacrylate injection into sacral insufficiency fractures. We report 2 cases of elderly patients with posttraumatic sacral insufficiency fractures, whose symptoms were completely relieved following CT-guided internal fixation by percutaneous polymethylmethacrylate injection. Under CT guidance, sacroplasty is a safe, practical, and effective solution to this underdiagnosed problem, with potential for comorbidities resulting in prolonged, costly hospital admissions for the elderly.


Correction of anisoplanatic phase errors in digital holography.
The quality of coherent images computed from digital holography or heterodyne array data is sensitive to phase errors of the reference and/or object beams. A number of algorithms exist for correcting phase errors in or very near the hologram plane. In the case of phase errors introduced a nonnegligible distance away from hologram plane, the resulting imagery exhibits anisoplanatism. A feature of coherent imaging is that such phase errors may be corrected by simply propagating the aberrated fields (from the object) from the hologram plane to the plane where the phase errors were introduced and applying the phase-error correction algorithms to the fields in that plane. We present experimental results that demonstrate correction of such anisoplanatic phase errors.


Palliative Care and Parkinson's Disease: Caregiver Perspectives.
Palliative care for Parkinson's disease (PD) is an emerging area of interest for clinicians, patients and families. Identifying the palliative care needs of caregivers is central to developing and implementing palliative services for families affected by PD. The objective of this paper was to elicit PD caregiver needs, salient concerns, and preferences for care using a palliative care framework. 11 PD caregivers and one non-overlapping focus group (n = 4) recruited from an academic medical center and community support groups participated in qualitative semi-structured interviews. Interviews and focus group discussion were digitally recorded, transcribed and entered into ATLAS.ti for coding and analysis. We used inductive qualitative data analysis techniques to interpret responses. Caregivers desired access to emotional support and education regarding the course of PD, how to handle emergent situations (e.g. falls and psychosis) and medications. Participants discussed the immediate impact of motor and non-motor symptoms as well as concerns about the future, including: finances, living situation, and caretaking challenges in advanced disease. Caregivers commented on the impact of PD on their social life and communication issues between themselves and patient. All participants expressed interest and openness to multidisciplinary approaches for addressing these needs. Caregivers of PD patients have considerable needs that may be met through a palliative care approach. Caregivers were receptive to the idea of multidisciplinary care in order to meet these needs. Future research efforts are needed to develop and test the clinical and cost effectiveness of palliative services for PD caregivers.


Local cerebral blood volume response to carbon dioxide in man.
We used an emission tomographic brain scanner to investigate the relationship between local cerebral blood volume (LCBV) and arterial blood carbon dioxide tension (PaCO2) in normal awake man. Measurements were made separately in three dimensions in various regions of grey and white matter, and the resting LCBV as well as the difference in sensitivity among these regions were compared. Over the range of PaCO2 studied (20-42 torr), the response of both the grey matter and the white matter to carbon dioxide was linear. The LCBV sensitivity of the grey matter to changes in PaCO2 was 0.053 ml/100 g per torr PaCO2 and in the white matter this sensitivity was 0.046 ml/100 g per torr PaCO2. These sensitivities were found not to be significantly different, yielding a slope of 0.049 ml/100 g per torr PaCO2 for the LCBV-PaCO2 curve for the entire brain. This is in excellent agreement with the other data for the whole brain. The resting cerebral blood volume of the grey matter at a PaCO2 of 34.4 torr, which was the average resting arterial carbon dioxide tension of the subjects, was 5.0 ml/100 g and was significantly higher than for white matter, which was 3.6 ml/100 g. At the local level, the cerebral blood volume of the frontal cortex is significantly less than that of the thalamus, whereas the frontoparietal cortex in the region of the sylvian fissure has a local cerebral blood volume significantly greater than that of the thalamus.


Simplified antiviral prophylaxis with or and without artificial feeding to reduce mother-to-child transmission of HIV in low and middle income countries: modelling positive and negative impact on child survival.
Antiviral prophylaxis is recommended for HIV positive mothers to prevent mother-to-child transmission of HIV. To date UNAIDS and WHO policy has been based on a study in Thailand which showed a reduction in transmission by half with short course AZT (Zidovudine) treatment together with artificial feeding. We modelled the possible positive and negative effects on child deaths in low and middle resource developing country settings of two interventions to reduce mother to child transmission (MTCT) of HIV: antenatal testing, short-course antivirals (zidovudine or nevirapine), firstly with and then without artificial feeding. Estimates are made of child lives likely to be saved by the programme by age ten years, balanced against increases in deaths due to more uninfected mothers choosing to use artificial feeds where these are part of the intervention. Mid-point values for variables affecting the balance of mortality gains and losses are taken from recent published data for low and middle income developing countries and a sensitivity analysis is undertaken. In low income settings the use of antivirals alone would result in an estimated gain in child survival of around 0.36%, representing 360 deaths avoided from a birth cohort of 100,000 by age 10 years. Adding artificial feeding could reduce the gain to 0.03% (30 deaths avoided). In middle income settings the gain from antivirals alone would be 0.26% but as 'spill-over' of artificial feeding to uninfected women was more likely it could result in a net increase of child deaths of up to 1.08% (1,080 additional deaths). A sensitivity analysis emphasised this potential for regimens using artificial feeding if progamme participation was low, and under most circumstances in middle income settings. HIV testing and use of antivirals by infected mothers, if well implemented, will be effective at a population level in reducing MTCT. However the addition of artificial feeding is potentially be a high risk strategy, especially in middle income countries.


An update on the Application of Nanotechnology in Bone Tissue Engineering.
Natural bone is a complex and hierarchical structure. Bone possesses an extracellular matrix that has a precise nano-sized environment to encourage osteoblasts to lay down bone by directing them through physical and chemical cues. For bone tissue regeneration, it is crucial for the scaffolds to mimic the native bone structure. Nanomaterials, with features on the nanoscale have shown the ability to provide the appropriate matrix environment to guide cell adhesion, migration and differentiation. This review summarises the new developments in bone tissue engineering using nanobiomaterials. The design and selection of fabrication methods and biomaterial types for bone tissue engineering will be reviewed. The interactions of cells with different nanostructured scaffolds will be discussed including nanocomposites, nanofibres and nanoparticles. Several composite nanomaterials have been able to mimic the architecture of natural bone. Bioceramics biomaterials have shown to be very useful biomaterials for bone tissue engineering as they have osteoconductive and osteoinductive properties. Nanofibrous scaffolds have the ability to provide the appropriate matrix environment as they can mimic the extracellular matrix structure of bone. Nanoparticles have been used to deliver bioactive molecules and label and track stem cells. Future studies to improve the application of nanomaterials for bone tissue engineering are needed.


Naloxone Distribution and Training for Patients with High-Risk Opioid Use in a Veterans Affairs Community-Based Primary Care Clinic.
Naloxone distribution has historically been implemented in a community-based, expanded public health model; however, there is now a need to further explore primary care clinic-based naloxone delivery to effectively address the nationwide opioid epidemic. To create a general medicine infrastructure to identify patients with high-risk opioid use and provide 25% of this population with naloxone autoinjector prescription and training within a 6-month period. The quality improvement study was conducted at an outpatient clinic serving 1238 marginally housed veterans with high rates of comorbid substance use and mental health disorders. Patients at high risk of opioid-related adverse events were identified using the Stratification Tool for Opioid Risk Management and were contacted to participate in a one-on-one, 15-minute, hands-on naloxone training led by nursing staff. The number of patients identified at high risk and rates of naloxone training/distribution. There were 67 patients identified as having high-risk opioid use. None of these patients had been prescribed naloxone at baseline. At the end of the intervention, 61 patients (91%) had been trained in the use of naloxone. Naloxone was primarily distributed by licensed vocational nurses (42/61, 69%). This study demonstrates the feasibility of high-risk patient identification and of a primary care-based and nursing-championed naloxone distribution model. This delivery model has the potential to provide access to naloxone to a population of patients with opioid use who may not be engaged in mental health or specialty care.


Pneumococcal meningitis in a young adult female with common variable immunodeficiency.
Female, 22 FINAL DIAGNOSIS: Pneumococcal meningitis Symptoms: Fever • headache • neck stiffness • nuchal rigidity • photophobia Ceftriaxone Clinical Procedure: - Specialty: Neurology. Rare disease. Common variable immunodeficiency (CVID) is a primary immunodeficiency associated with hypogammaglobulinemia and other various clinical manifestations. It is a rare disease with a prevalence of CVID is approximately 1: 50,000-200,000. Clinical manifestations of CVID include recurrent bacterial infections, autoimmune, gastrointestinal, lymphoproliferative, granulomatous, and malignancy. Twenty-two year-old Hispanic female presented with a throbbing headache, nuchal rigidity, photophobia and a high grade fever. Lumbar puncture with CSF assessment revealed a turbid fluid with WBC of 6937 per uL, polymorphnuclear cells of 81%, protein 248 mg/dL, glucose <3 mg/Dl. CSF antigens were positive for Streptococcus pneumonia and CSF culture grew pansensitive Strepococcus pneumonia. Immunoglobin (Ig) levels of IgA, IgE, IgG and IgM were all decreased. Absolute cell counts of CD3, CD4 and CD8 were all low. Bone marrow biopsy was normocellular. Excisional lymph node biopsy revealed lymph nodes with reactive follicular hyperplasia. Common variable immunodeficiency disease (CVID) was diagnosed based on exclusion. IVIG therapy was given and patient received a two-week course of ceftriaxone. THE DIAGNOSIS OF CVID IS MADE BASED ON THE FOLLOWING CRITERIA: 1) Marked decrease of IgG and at least one of the IgM or IgA isotypes. 2) The onset of immunodeficiency at greater than 2 years old. 3) Absence of isohemagglutinins and/or poor response to vaccines 4) Exclusion of other defined causes of hypogammaglobulinemia. A definite diagnosis is often late because it is wrongly assumed that primary immunodeficiencies are extremely rare, hence many patients are already seriously ill at the time of presentation.


High prevalence of neurocysticercosis among patients with epilepsy in a tertiary care hospital of Assam, India.
Neurocysticercosis (NCC) is a parasitic disease of the central nervous system, which is caused by the metacestode of the pork tapeworm, Taenia solium. The present unicentric, hospital-based, cross-sectional study was undertaken to assess the contribution of NCC as a cause of active epilepsy among patients attending a tertiary health care center in Assam, India. Over a period of 2 years, 152 active epilepsy patients were investigated based on clinical, epidemiological, neuroimaging (contrast-enhanced computerized tomography), and immunological techniques to establish the diagnosis of NCC. A precoded questionnaire was administered to patients and/or guardians to collect detailed medical history. Ninety-three cases (61.2%) fulfilled either definitive or probable diagnostic criteria for NCC. Anti-cysticercus immunoglobulin G antibodies were detected by ELISA and enzyme electro-immune transfer blot in 69 (45.4%) active epilepsy patients. Seroprevalence was higher in males, 46.6% (54/116); than in females, 41.7% (15/36), and increased significantly with age; peaking in the 20-39 years age group (36/76; χ2 = 5.64; P = 0.02). Among the seropositive cases, 54 (78.3%) were diagnosed with NCC. A significantly higher number of seropositive individuals were diagnosed with NCC in the 20-39 years age group as compared to the 40 years and above age group (χ2 = 6.28; P = 0.01). The association between seropositivity for NCC, and the number of lesions in the brain was statistically significant (χ2 = -8.33; P = 0.003). This study indicates that NCC is a major cause of active epilepsy in Assam. A high prevalence of pediatric NCC is also a major concern.


Reporting of Sepsis Cases for Performance Measurement Versus for Reimbursement in New York State.
Under "Rory's Regulations," New York State Article 28 acute care hospitals were mandated to implement sepsis protocols and report patient-level data. This study sought to determine how well cases reported under state mandate align with discharge records in a statewide administrative database. Observational cohort study. First 27 months of mandated sepsis reporting (April 1, 2014, to June 30, 2016). Hospitalizations with sepsis at New York State Article 28 acute care hospitals. Sepsis regulations with mandated reporting. We compared cases reported to the New York State Department of Health Sepsis Clinical Database with discharge records in the Statewide Planning and Research Cooperative System database. We classified discharges as 1) "coded sepsis discharges"-a diagnosis code for severe sepsis or septic shock and 2) "possible sepsis discharges," using Dombrovskiy and Angus criteria. Of 111,816 sepsis cases reported to the New York State Department of Health Sepsis Clinical Database, 105,722 (94.5%) were matched to discharge records in Statewide Planning and Research Cooperative System. The percentage of coded sepsis discharges reported increased from 67.5% in the first quarter to 81.3% in the final quarter of the study period (mean, 77.7%). Accounting for unmatched cases, as many as 82.7% of coded sepsis discharges were potentially reported, whereas at least 17.3% were unreported. Compared with unreported discharges, reported discharges had higher rates of acute organ dysfunction (e.g., cardiovascular dysfunction 63.0% vs 51.8%; p < 0.001) and higher in-hospital mortality (30.2% vs 26.1%; p < 0.001). Hospital characteristics (e.g., number of beds, teaching status, volume of sepsis cases) were similar between hospitals with a higher versus lower percent of discharges reported, p values greater than 0.05 for all. Hospitals' percent of discharges reported was not correlated with risk-adjusted mortality of their submitted cases (Pearson correlation coefficient 0.11; p = 0.17). Approximately four of five discharges with a diagnosis code of severe sepsis or septic shock in the Statewide Planning and Research Cooperative System data were reported in the New York State Department of Health Sepsis Clinical Database. Incomplete reporting appears to be driven more by underrecognition than attempts to game the system, with minimal bias to risk-adjusted hospital performance measurement.


How genetically engineered mouse tumor models provide insights into human cancers.
Genetically engineered mouse models (GEMMs) of human cancer were first created nearly 30 years ago. These early transgenic models demonstrated that mouse cells could be transformed in vivo by expression of an oncogene. A new field emerged, dedicated to generating and using mouse models of human cancer to address a wide variety of questions in cancer biology. The aim of this review is to highlight the contributions of mouse models to the diagnosis and treatment of human cancers. Because of the breadth of the topic, we have selected representative examples of how GEMMs are clinically relevant rather than provided an exhaustive list of experiments. Today, as detailed here, sophisticated mouse models are being created to study many aspects of cancer biology, including but not limited to mechanisms of sensitivity and resistance to drug treatment, oncogene cooperation, early detection, and metastasis. Alternatives to GEMMs, such as chemically induced or spontaneous tumor models, are not discussed in this review.


Infectious disease mortality in two Outer Hebridean islands: 1. measles, pertussis and influenza.
The purpose of the study was to examine changes in mortality from measles, pertussis (whooping cough) and influenza (all epidemic diseases) in Harris and Barra, two Outer Hebridean islands, from 1855 to 1990, and to compare the findings with those from Scotland as a whole over the same period. It was also intended to relate changes in mortality to those in social and economic factors. Ages and causes of death in Harris and Barra were ascertained from copies of death certificates held at the General Register Office, Edinburgh, and for Scotland as a whole from the Annual Reports of the Registrars General for Scotland. Data were standardized by calculating the Proportionate Mortality Ratio (PMR), the proportion of deaths due to a particular cause to all deaths over a given period. Spectral analysis was employed to examine the durations of epidemic cycles. Ages at death increased slightly over the period of the study. For measles and pertussis, other than for the former in Harris, there were significant relationships between numbers of deaths per decade, and numbers of new susceptibles, estimated as the numbers of births. Epidemics of measles and pertussis in the islands occurred at intervals, usually separated by years of no mortality. The highest PMRs were generally during the later decades of the 19th and first decade of the 20th centuries; this may have been related to the economic problems of agriculture and fishing, and to increasing population density. Influenza epidemics were more frequent than those of the other two diseases. For all three diseases in both islands, there were significant negative power relationships between epidemic size and frequency of occurrence; those in Harris were the stronger. The relationships between length and frequency were significant only in Harris. Generally, epidemic lengths seemed less variable than sizes, possibly because of the rather 'coarse' units of length (quarters) employed. Spectral analysis of the 'detrended' data for the period before the introduction of specific immunoprophylaxis revealed that for measles the main epidemic cycle in all three populations was between 7.3 and 7.8 years' duration. Barra and Scotland had additional 2.5- and 2-year cycles, respectively. For pertussis, Harris and Barra had main cycles of 7.4 years. Harris had an additional cycle of 3.2 years. Scotland had cycles of 4 and 2 years. For influenza, Harris had a main cycle length of 7.4 years, and a less-defined one of about 2.6 years. Barra had a main cycle of 6.9 years, and a subsidiary one of 2 years. Scotland has a single cycle of 8 years. Cubic regressions of the spectral densities on cycle frequencies showed large coefficients for Harris and Barra, but small ones for Scotland. Measles coefficients were closely similar in the two islands, but not those for pertussis. The findings demonstrate the episodic occurrence of epidemics of these three diseases in the two islands, as against their continual presence in the much larger population of Scotland. They reveal also the decreasing importance of these causes of death in all three populations. The data from Harris and Barra suggest that measles is a more epidemiologically 'stable' disease than pertussis. Both islands appear to obey Hamer's law of 'mass action'. The relatively long intervals between epidemics in the islands may be due partly to their isolation, and partly to the slow accumulation of sufficient numbers of susceptibles to enable an epidemic to occur.


[Reducing the burden of disease caused by alcohol use in Peru: evidence- based approaches].
Alcohol use is one the most important risk factors for illness and early death in Peru. Measures aimed at decreasing or controlling the great impact caused by alcohol in the Peruvian society are urgently needed. This article identifies and promotes the implementation of public health measures supported by sound scientific evidence of effectiveness or, in some cases, cost-effectiveness. The 10 evidence-based public health measures identified and described here represent a set if measures with high probability of success if implemented, as they are supported by scientific evidence. We recommend that governments, at the national or local levels, apply these measures not individually, but in combination, arranging them into a plan or roadmap, where the framework in which they will be applied must be established according to each context. Considering the available resources, some of these measures could be implemented in the short and medium term while the others can be set in the long-term.


Genomic variation landscape of the human gut microbiome.
Whereas large-scale efforts have rapidly advanced the understanding and practical impact of human genomic variation, the practical impact of variation is largely unexplored in the human microbiome. We therefore developed a framework for metagenomic variation analysis and applied it to 252 faecal metagenomes of 207 individuals from Europe and North America. Using 7.4 billion reads aligned to 101 reference species, we detected 10.3 million single nucleotide polymorphisms (SNPs), 107,991 short insertions/deletions, and 1,051 structural variants. The average ratio of non-synonymous to synonymous polymorphism rates of 0.11 was more variable between gut microbial species than across human hosts. Subjects sampled at varying time intervals exhibited individuality and temporal stability of SNP variation patterns, despite considerable composition changes of their gut microbiota. This indicates that individual-specific strains are not easily replaced and that an individual might have a unique metagenomic genotype, which may be exploitable for personalized diet or drug intake.


[Deaths by homicide in Mexico: trends, socio-geographical variations and associated factors].
This study seeks to analyze the trend of homicide rates (total and by firearm) in Mexico between 1990 and 2009 and identify the variables that best explain the geographical variations of these rates in the 2008-2009 two-year period. Homicide rates, adjusted for age, were calculated for both sexes between 1990 and 2009 and for each state in 2008-2009. Factors associated with the interstate variations in the homicide rates were identified using multiple linear regression analysis. Results show that the homicide rate in Mexico decreased between 1990 and 2007, but doubled over the last two years (from 7.6 to 16.6 per 100,000). In 2009, the male homicide rate was almost 9 times higher than the female rate and about two-thirds of homicides involved firearms. Multivariate analysis reveals that impunity, drug trafficking, alcohol and drug consumption and school dropout in basic education - in that order - are key factors for understanding the geographical variations in homicide rates in Mexico in 2008-2009. Findings suggest that to reduce the number of homicide victims and spatial variations in the rate, it is necessary not only to fight the drug cartels, but above all to implement structural reforms in the criminal justice system and reduce the socioeconomic disparities among states.