Neighborhood Interventions to Reduce Violence.
Violence is a widespread problem that affects the physical, mental, and social health of individuals and communities. Violence comes with an immense economic cost to its victims and society at large. Although violence interventions have traditionally targeted individuals, changes to the built environment in places where violence occurs show promise as practical, sustainable, and high-impact preventive measures. This review examines studies that use quasi-experimental or experimental designs to compare violence outcomes for treatment and control groups before and after a change is implemented in the built environment. The most consistent evidence exists in the realm of housing and blight remediation of buildings and land. Some evidence suggests that reducing alcohol availability, improving street connectivity, and providing green housing environments can reduce violent crimes. Finally, studies suggest that neither transit changes nor school openings affect community violence.


Glycolytic controls in estivation and anoxia: a comparison of metabolic arrest in land and marine molluscs.
Facultative metabolic rate depression is the common adaptive strategy underlying various animal mechanisms for surviving harsh environmental conditions. This strategy is common among molluscs, enabling animals to survive over days or even months in the absence of oxygen or under extremely dry conditions. The large reductions in metabolic rate during estivation and anoxia can translate into considerable energy savings when dormant animals are compared to active animals. A complex metabolic coordination is required during the transition into the dormant state to maintain cellular homeostasis and involves both energy-consuming and energy-producing pathways. With regard to energy-producing pathways, several different mechanisms have been identified that participate in controlling flux. One such mechanism, enzyme phosphorylation, can have a wide-ranging effect. For example, phosphorylated enzymes exhibit altered substrate, activator, and inhibitor affinities. This effect may be magnified by changes in the concentrations of allosteric effectors, such as fructose 2,6-bisphosphate, that occur during hypometabolic states. Changes in fructose 2,6-bisphosphate are related to changes in enzyme phosphorylation through changes in the relative activity of phosphofructokinase-2. Alterations in glycolytic enzyme binding can also be brought about through changes in enzyme phosphorylation. The present review focuses on identifying hypometabolism-related changes in enzyme phosphorylation as well as characterizing the mechanisms involved in mediating these phosphorylation events.


Lichen planus occurring after influenza vaccination: report of three cases and review of the literature.
Although influenza vaccine is thought to be effective and safe, it occasionally causes systemic reactions such as toxic epidermal necrolysis, bullous pemphigoid, lichen planus (LP), etc. The period of increased risk of developing these events was different depending on the immune responses induced by the vaccination. We report 3 cases of LP which appeared after an influenza vaccination. Our cases indicate that the period of increased risk of developing vaccine-related LP was concentrated within 2 weeks after vaccination, and that the vaccine alone represents a triggering factor necessary for immune alteration sufficient for the development of LP. Because these adverse events tend to develop over a predictable time course, the time of onset may give an important clue to the diagnosis of vaccine-related diseases. We suggest that a history of recent vaccination should be sought in all patients presenting with linear LP.


Using the Technology Acceptance Model to explore community dwelling older adults' perceptions of a 3D interior design application to facilitate pre-discharge home adaptations.
In the UK occupational therapy pre-discharge home visits are routinely carried out as a means of facilitating safe transfer from the hospital to home. Whilst they are an integral part of practice, there is little evidence to demonstrate they have a positive outcome on the discharge process. Current issues for patients are around the speed of home visits and the lack of shared decision making in the process, resulting in less than 50 % of the specialist equipment installed actually being used by patients on follow-up. To improve practice there is an urgent need to examine other ways of conducting home visits to facilitate safe discharge. We believe that Computerised 3D Interior Design Applications (CIDAs) could be a means to support more efficient, effective and collaborative practice. A previous study explored practitioners perceptions of using CIDAs; however it is important to ascertain older adult's views about the usability of technology and to compare findings. This study explores the perceptions of community dwelling older adults with regards to adopting and using CIDAs as an assistive tool for the home adaptations process. Ten community dwelling older adults participated in individual interactive task-focused usability sessions with a customised CIDA, utilising the think-aloud protocol and individual semi-structured interviews. Template analysis was used to carry out both deductive and inductive analysis of the think-aloud and interview data. Initially, a deductive stance was adopted, using the three pre-determined high-level themes of the technology acceptance model (TAM): Perceived Usefulness (PU), Perceived Ease of Use (PEOU), Actual Use (AU). Inductive template analysis was then carried out on the data within these themes, from which a number of sub-thmes emerged. Regarding PU, participants believed CIDAs served as a useful visual tool and saw clear potential to facilitate shared understanding and partnership in care delivery. For PEOU, participants were able to create 3D home environments however a number of usability issues must still be addressed. The AU theme revealed the most likely usage scenario would be collaborative involving both patient and practitioner, as many participants did not feel confident or see sufficient value in using the application autonomously. This research found that older adults perceived that CIDAs were likely to serve as a valuable tool which facilitates and enhances levels of patient/practitioner collaboration and empowerment. Older adults also suggested a redesign of the interface so that less sophisticated dexterity and motor functions are required. However, older adults were not confident, or did not see sufficient value in using the application autonomously. Future research is needed to further customise the CIDA software, in line with the outcomes of this study, and to explore the potential of collaborative application patient/practitioner-based deployment.


A new zero-inflated negative binomial methodology for latent category identification.
We introduce a new statistical procedure for the identification of unobserved categories that vary between individuals and in which objects may span multiple categories. This procedure can be used to analyze data from a proposed sorting task in which individuals may simultaneously assign objects to multiple piles. The results of a synthetic example and a consumer psychology study involving categories of restaurant brands illustrate how the application of the proposed methodology to the new sorting task can account for a variety of categorization phenomena including multiple category memberships and for heterogeneity through individual differences in the saliency of latent category structures.


Effects of Ovarian Cycle on Hemodynamic Responses during Dynamic Exercise in Sedentary Women.
This study tested the hypothesis that effects of the menstrual cycle on resting blood pressure carry over to dynamic exercise. Eleven healthy females were studied during the early (EP; low estrogen, low progesterone) and late follicular (LP; high estrogen, low progesterone) menstrual phases. Stroke volume (SV), heart rate (HR), cardiac output (CO), systolic blood pressure (SBP), diastolic blood pressure (DBP), and total vascular conductance (TVC) were assessed at rest and in response to mild and moderate cycling exercise during EP and LP. During EP, compared to LP, baseline SBP (111±1 vs. 103±2 mmHg), DBP (71±2 vs. 65±2 mmHg) and mean arterial pressure (MAP) (84±2 vs. 78±1 mmHg) were higher and TVC (47.0±1.5 vs. 54.9±4.2 ml/min/mmHg) was lower (p<0.05). During exercise, absolute values of SBP (Mild: 142±4 vs. 127±5 mmHg; Moderate: 157±4 vs. 144±5 mmHg) and MAP (Mild: 100±3 vs. 91±3 mmHg; Moderate: 110±3 vs. 101±3 mmHg) were also higher, while TVC was lower (Mild: 90.9±5.1 vs. 105.4±5.2 ml/min/mmHg; Moderate: 105.4±5.3 vs. 123.9±8.1 ml/min/mmHg) during EP (p<0.05). However, exercise-induced increases in SBP, MAP and TVC at both work intensities were similar between the two menstrual phases, even though norepinephrine concentrations were higher during LP. Results indicate that blood pressure during dynamic exercise fluctuates during the menstrual cycle. It is higher during EP than LP and appears to be due to additive effects of simultaneous increases in baseline blood pressure and reductions in baseline TVC.


Preoperative and intraoperative assessment of myometrial invasion in endometrial cancer: comparison of magnetic resonance imaging and frozen sections.
To compare the diagnostic characteristics of the evaluation of myometrial invasion (MI) retrospectively between preoperative magnetic resonance imaging (MRI) and intraoperative frozen sections. A retrospective study. University hospital. 201 women diagnosed with endometrial carcinoma. All women underwent preoperative MRI and 111 of them also underwent intraoperative frozen section assessment. The final pathological evaluation was used as the definitive diagnosis. In women who underwent MRI and frozen sections (n = 111), the accuracies of detection of MI and of deep invasion (defined as ≥50% invasion) were compared. The accuracy, sensitivity, and specificity of MRI for detection of MI were 65.8, 58.8, and 88.5%, and those in frozen sections were 90.1, 90.6, and 88.5%, respectively. The accuracy and sensitivity of frozen sections were significantly higher (p < 0.001, p < 0.001), whereas the specificity of the two methods did not differ (p = 1.000). The accuracy, sensitivity, and specificity of MRI for detection of deep invasion were 83.8, 69.2, and 88.2%, and those of frozen sections were 93.7, 73.1, and 100.0%, respectively. The accuracy and specificity of frozen sections were significantly higher (p = 0.007 and p < 0.001, respectively), whereas sensitivity did not show a significant difference (p = 0.999). In assessment of MI, the accuracy of frozen sections was significantly higher than that of MRI. Since the diagnostic characteristics differ between two methods, additional intraoperative frozen sections are recommended for more accurate assessment of MI when MRI is negative for the presence of any MI or positive for the presence of deep invasion.


Monitoring the formation of PtNi nanoalloys supported on hollow graphitic spheres using in situ pair distribution function analysis.
This article aims to address the formation and the structural disordering/ordering phenomena of PtNi nanoalloys supported on hollow graphitic spheres (HGSs) using pair distribution function (PDF) analysis under ex situ/in situ data collection conditions. Starting from small nanoparticles (10-15 Å in diameter) embedded in HGSs, structural changes were monitored during stepwise heating and cooling of the sample using in situ PDF analysis. In order to evaluate the conventional synthesis route for the production of PtNi nanoalloys supported on HGSs, ex situ PDF experiments were performed before and after heat treatment in a furnace. The studies demonstrate that the local structure of the in situ synthesised PtNi nanoalloy differs from its ex situ synthesised counterpart. A partially ordered PtNi nanoalloy was obtained during the stepwise in situ cooling of the precursor, whereas the conventional ex situ synthesis route did not lead to the formation of an ordered crystal structure. In this study we could show that rapid heating and cooling results in a disordered PtNi alloy whereas slow heating and cooling leads to disorder-order transitions in PtNi.


Anisotropic particles with patchy, multicompartment and Janus architectures: preparation and application.
Anisotropic particles, such as patchy, multicompartment and Janus particles, have attracted significant attention in recent years due to their novel morphologies and diverse potential applications. The non-centrosymmetric features of these particles make them a unique class of nano- or micro-colloidal materials. Patchy particles usually have different compositional patches in the corona, whereas multicompartment particles have a multi-phasic anisotropic architecture in the core domain. In contrast, Janus particles, named after the double-faced Roman god, have a strictly biphasic geometry of distinct compositions and properties in the core and/or corona. The term Janus particles, multicompartment particles and patchy particles frequently appears in the literature, however, they are sometimes misused due to their structural similarity. Therefore, in this critical review we classify the key features of these different anisotropic colloidal particles and compare structural properties as well as discuss their preparation and application. This review brings together and highlights the significant advances in the last 2 to 3 years in the fabrication and application of these novel patchy, multicompartment and Janus particles (98 references).


Asthma and depression: a pragmatic review of the literature and recommendations for future research.
Although the association between asthma and psychosocial factors has long been recognised, it is only in the last decade that the impact of coexisting asthma and depression has become the focus of considerable research interest. However, the findings so far have been confusing and often contradictory. This paper sets out a methodical review and appraisal of the literature to date, including suggestions for future research. PubMed and PsycINFO databases were used to search for English-language articles relating to asthma and depression research. The resulting articles were then reviewed and summarised, creating a report that was used to develop research recommendations. The main findings from this review included: (a) results are mixed as to whether persons with asthma are more likely to be depressed than those without asthma; (b) asthma and depression may have an 'additive' adverse effect on the normal asthma-related quality of life reductions; (c) subjective measures of asthma severity may be more strongly related to depression than objective measures; (d) specific asthma symptoms appear to be linked to depression; (e) sadness and depression can produce respiratory effects consistent with asthma exacerbations; (f) depression appears to be negatively related to asthma treatment compliance; (g) corticosteroid use in asthma treatment has been associated with depression, though it is unclear how common this problem is in real life; (h) interventions that address the physical, psychological, and social consequences of asthma are likely to lead to the most successful treatment outcomes; (i) treating the depression of individuals with asthma is likely to minimise the negative effects of the coexistence; and (j) a number of common methodological problems were observed in the literature. There is a large amount of research yet to be undertaken to clarify issues around asthma and depression, with the overdue next step being to design integrated treatment approaches, and carry out large-scale prospective studies to determine the impact of using such approaches to treat individuals with depression and asthma. Such studies will be the only way in which some fundamental questions about the development and coexistence of these two conditions will be answered.


Neuroprotection Offered by Majun Khadar, a Traditional Unani Medicine, during Cerebral Ischemic Damage in Rats.
Stroke results in damages to many biochemical, molecular and behavioral deficits. Present study provides evidence of the protective efficacy of a Unani herbal medicine, Majun Khadar (MK), against cerebral ischemia-induced behavioral dysfunctions and neurochemical alterations in the hippocampus (HIP). Transient focal cerebral ischemia was induced for 2 h followed by reperfusion for 22 h in a rat model. Rats were divided into four groups: sham, middle cerebral artery occluded (MCAO), drug sham (MK; 0.816 g kg(-1) orally for 15 days) and MK pre-treated ischemic group (MK + MCAO). Levels of enzymatic and non-enzymatic antioxidants were estimated in HIP along with behavioral testing. MK pre-treatment significantly (P < .05-.001) restored the activities of glutathione peroxidase (GP×), glutathione reductase (GR), glutathione S-transferase (GST) and decreased the level of lipid peroxidation (LPO) and H2O2 content in HIP in the MK + MCAO group which were severely altered in the MCAO group. The content of glutathione (GSH), total thiols (TT) and ascorbic acid (AsA) was significantly depleted in the MCAO group; pretreatment with MK was able to restore its levels. Also in the MK + MCAO group, significant (P < .5-.001) recovery in behavioral testing by rota rod and open-field activities was seen as compared with the MCAO group. MK alone did not show any change neither in the status of various antioxidants nor behavioral functions over sham values. Although detailed studies are required for the evaluation of exact neuroprotective mechanism of MK against cerebral ischemia these preliminary experimental findings conclude that MK exhibits neuroprotective effect in cerebral ischemia by potentiating the antioxidant defense system of the brain.


How amino and nitro substituents direct electrophilic aromatic substitution in benzene: an explanation with Kohn-Sham molecular orbital theory and Voronoi deformation density analysis.
The substituent effect of the amino and nitro groups on the electronic system of benzene has been investigated quantum chemically using quantitative Kohn-Sham molecular orbital theory and a corresponding energy decomposition analysis (EDA). The directionality of electrophilic substitution in aniline can accurately be explained with the amount of contribution of the 2pz orbitals on the unsubstituted carbon atoms to the highest occupied π orbital. For nitrobenzene, the molecular π orbitals cannot explain the regioselectivity of electrophilic substitution as there are two almost degenerate π orbitals with nearly the same 2pz contributions on the unsubstituted carbon atoms. The Voronoi deformation density analysis has been applied to aniline and nitrobenzene to obtain an insight into the charge rearrangements due to the substituent. This analysis method identified the orbitals involved in the C-N bond formation of the π system as the cause for the π charge accumulation at the ortho and para positions in the case of the NH2 group and the largest charge depletion at these same positions for the NO2 substituent. Furthermore, we showed that it is the repulsive interaction between the πHOMO of the phenyl radical and the πHOMO of the NH2 radical that is responsible for pushing up the πHOMO of aniline and therefore activating this π orbital of the phenyl ring towards electrophilic substitution.


Development of visuo-auditory integration in space and time.
Adults integrate multisensory information optimally (e.g., Ernst and Banks, 2002) while children do not integrate multisensory visual-haptic cues until 8-10 years of age (e.g., Gori et al., 2008). Before that age strong unisensory dominance occurs for size and orientation visual-haptic judgments, possibly reflecting a process of cross-sensory calibration between modalities. It is widely recognized that audition dominates time perception, while vision dominates space perception. Within the framework of the cross-sensory calibration hypothesis, we investigate visual-auditory integration in both space and time with child-friendly spatial and temporal bisection tasks. Unimodal and bimodal (conflictual and not) audio-visual thresholds and PSEs were measured and compared with the Bayesian predictions. In the temporal domain, we found that both in children and adults, audition dominates the bimodal visuo-auditory task both in perceived time and precision thresholds. On the contrary, in the visual-auditory spatial task, children younger than 12 years of age show clear visual dominance (for PSEs), and bimodal thresholds higher than the Bayesian prediction. Only in the adult group did bimodal thresholds become optimal. In agreement with previous studies, our results suggest that also visual-auditory adult-like behavior develops late. We suggest that the visual dominance for space and the auditory dominance for time could reflect a cross-sensory comparison of vision in the spatial visuo-audio task and a cross-sensory comparison of audition in the temporal visuo-audio task.


Plasma alkylresorcinols, biomarkers of whole-grain wheat and rye intake, and incidence of colorectal cancer.
Few studies have investigated the association between whole-grain intake and colorectal cancer. Because whole-grain intake estimation might be prone to measurement errors, more objective measures (eg, biomarkers) could assist in investigating such associations. The association between alkylresorcinols, biomarkers of whole-grain rye and wheat intake, and colorectal cancer incidence were investigated using prediagnostic plasma samples from colorectal cancer case patients and matched control subjects nested within the European Prospective Investigation into Cancer and Nutrition. We included 1372 incident colorectal cancer case patients and 1372 individual matched control subjects and calculated the incidence rate ratios (IRRs) for overall and anatomical subsites of colorectal cancer using conditional logistic regression adjusted for potential confounders. Regional differences (Scandinavia, the Mediterranean, Central Europe) were also explored. High plasma total alkylresorcinol concentration was associated with lower incidence of distal colon cancer; the adjusted incidence rate ratio of distal colon cancer for the highest vs lowest quartile of plasma total alkylresorcinols was 0.48 (95% confidence interval [CI] = 0.28 to 0.83). An inverse association between plasma total alkylresorcinol concentrations and colon cancer was found for Scandinavian participants (IRR per doubling = 0.83; 95% CI = 0.70 to 0.98). However, plasma total alkylresorcinol concentrations were not associated with overall colorectal cancer, proximal colon cancer, or rectal cancer. Plasma alkylresorcinols concentrations were associated with colon and distal colon cancer only in Central Europe and Scandinavia (ie, areas where alkylresorcinol levels were higher). High concentrations of plasma alkylresorcinols were associated with a lower incidence of distal colon cancer but not with overall colorectal cancer, proximal colon cancer, and rectal cancer.


Structural basis for the cytoskeletal association of Bcr-Abl/c-Abl.
The Bcr-Abl tyrosine kinase causes different forms of leukemia in humans. Depending on its position within the cell, Bcr-Abl differentially affects cellular growth. However, no structural and molecular details for the anticipated localization determinants are available. We present the NMR structure of the F-actin binding domain (FABD) of Bcr-Abl and its cellular counterpart c-Abl. The FABD forms a compact left-handed four-helix bundle in solution. We show that the nuclear export signal (NES) previously reported in this region is part of the hydrophobic core and nonfunctional in the intact protein. In contrast, we could identify the critical residues of helix alphaIII that are responsible for F-actin binding and cytoskeletal association. We propose that these interactions represent a major determinant for both Bcr-Abl and c-Abl localization.


A New Handheld Device for the Detection of Falsified Medicines: Demonstration on Falsified Artemisinin-Based Therapies from the Field.
AbstractPoor-quality medicines are a major problem for health-care systems in resource-poor settings as identifying falsified medicines requires a complex laboratory infrastructure such as a Medicines Quality Control Laboratory. We report here an evaluation of a low-cost, handheld near-infrared spectrometer (NIRS) device by analyzing a library of artemisinin-based combination therapy (ACT) medicines to determine its usefulness as a drug-screening tool. The "SCiO" research prototype device was used to collect NIR spectra of a library of ACT and artesunate monotherapy medicine samples previously collected in Bioko Island and Equatorial Guinea and Kintampo, Ghana. The quality of these samples had been categorized as falsified, substandard, and quality assured based on the amount of stated active pharmaceutical ingredients detected using high-performance liquid chromatography photodiode array. Numerical analyses were performed on the NIR spectra to assess the usefulness of NIR to identify falsified and substandard medicines. The NIRS device was successful at detecting falsified medicines in all cases where the library contained both quality assured and falsified medicines of the same stated brand of medicines. The NIRS device was successful at identifying substandard amounts of artesunate but not amodiaquine in the ACT samples (N = 15) of artesunate-amodiaquine. This work reveals that this low-cost, portable NIRS device is promising for screening ACTs for falsified samples and could enable widespread drug screening at all points of the health system.


An epidemic of yellow fever in Central Brazil, 1972-1973. II. Ecological studies.
Results of ecological studies undertaken during the 1972-1973 epidemic of yellow fever (YF) in Goiás State, Brazil, suggest that mosquitoes of the genus Haemagogus were the only vectors infected with YF virus. Nine isolations of the agent were made from 1,688 Haemagogus spp. caught within or near forests from 27 January to 3 March 1973. Seven of these isolations cane from mosquitoes collected on the forest floor. No YF virus isolation was made from 791 Haemagogus leucocelaenus or 1,096 Sabethes chloropterus. Haemagogus were caught both in and outside houses located 500 m from the forest, although at a lower rate than in the forest. Haemagogus collection rates in a secondary growth forest were similar to or even higher than those in primary forests. YF virus was recovered from a Cebus monkey and hemagglutination-inhibition and/or neutralizing antibody to YF virus was found in seven (30.4%) of 23 primates examined. There was, however, little evidence of sick or dying monkeys. Among other wild-caught animals only a single marsupial (Caluromys) had antibodies to the virus. These data show that sylvan YF is not confined to the forest, nor always associated with conspicuous epizootics.


Kinetics and Mechanisms of Ciprofloxacin Oxidation on Hematite Surfaces.
Adsorption of antibiotics at mineral surfaces has been extensively studied over the past 20 years, yet much remains to be learned on their interfacial properties and transformation mechanisms. In this study, interactions of Ciprofloxacin (CIP), a fluoroquinolone antibiotic with two sets of synthetic nanosized hematite particles, with relatively smooth (H10, 10-20 nm in diameter) and roughened (H80, 80-90 nm in diameter) surfaces, were studied by means of liquid chromatography (LC), mass spectrometry (MS), and spectroscopy (vibration and X-ray photoelectron). Attenuated Total Reflectance Fourier Transform Infrared (ATR-FTIR) spectroscopy provides evidence for inner-sphere bidentate complex formation of CIP at hematite surfaces in 0.01 M NaCl, irrespective of pH and particle size. ATR-FTIR spectroscopy also revealed that the sorbed mother CIP molecule decayed to other surface species over a period of at least 65 h. This was supported by the detection of three daughter products in the aqueous phase by LC/MS. The appearance of NH3(+) groups during the course of these experiments, revealed by cryogenic XPS, provides further evidence that CIP oxidation proceeds through an opening of piperazine ring via N-dealkylation. Additional in vacuo FTIR experiments under temperature-programmed desorption also showed that oxidation of sorbed byproducts were effectively degraded beyond 450 °C, a result denoting considerably strong (inter)molecular bonds of both mother and daughter products. This work also showed that rougher, possibly multidomainic particles (H80) generated slower rates of CIP decomposition but occurring through more complex schemes than at smoother particle surfaces (H10). This work thus uncovered key aspects of the binding of an important antibiotic at iron oxide surfaces, and therefore provided additional constraints to our growing understanding of the fate of emerging contaminants in the environment.


Wrong-level surgery: A unique problem in spine surgery.
Even though a lot of effort has gone into preventing operating at the wrong site and wrong patient, wrong-level surgery is a unique problem in spine surgery. The current method to prevent wrong level spine surgery performed is mainly relied on intra-operative X-ray. Unfortunately, because of the unique features and anatomy of the spinal column, wrong level spine surgery still happens. There are situations that even with intraoperative X-ray, correct level still cannot be reliably identified. Examples of patient whose surgery can easily be performed on the wrong level are illustrated. A protocol to prevent wrong-level spine surgery preformed is developed. The consequence of wrong-level spine surgery not only generates another surgery of the intended level; it is usually also associated with lawsuit. Strictly following this protocol can prevent wrong-level spine surgery.


Diffraction of evanescent plane waves by a resistive half-plane.
Diffraction of evanescent plane waves by a resistive half-plane is examined. The scattering integrals are constructed with the modified theory of physical optics. These integrals are evaluated uniformly by using an unusual method. The scattered fields of evanescent waves are obtained by giving the angle of incidence a complex value. The diffracted waves are plotted numerically for different parameters of the incident field.


OmpF enhances the ability of BtuB to protect susceptible Escherichia coli cells from colicin E9 cytotoxicity.
The outer membrane (OM) vitamin B(12) receptor, BtuB, is the primary receptor for E group colicin adsorption to Escherichia coli. Cell death by this family of toxins requires the OM porin OmpF but its role remains elusive. We show that OmpF enhances the ability of purified BtuB to protect bacteria against the endonuclease colicin E9, demonstrating either that the two OM proteins form the functional receptor or that OmpF is recruited for subsequent translocation of the bacteriocin. While stable binary colicin E9-BtuB complexes could be readily shown in vitro, OmpF-containing complexes could not be detected, implying that OmpF association with the BtuB-colicin complex, while necessary, must be weak and/or transient in nature.


Demographic and clinical factors related to ostomy complications and quality of life in veterans with an ostomy.
The purpose of this study is to describe demographic, clinical, and quality-of-life variables related to ostomy complications (skin irritation, leakage, and difficulty adjusting to an ostomy) in a veteran population in the United States. The original study employed a descriptive crosssectional study using a mixed method design. This secondary analysis used the quantitative data collected. Two hundred thirty-nine veterans with intestinal ostomies from 3 Veteran's Administration hospitals participated in the study. Instruments used for this investigation included the City of Hope Quality of Life: Ostomy Instrument. Demographic and medical history data were collected from the survey, the Veteran's Administration health information system, and the Tumor Registry database. A self-administered survey questionnaire (mCOH-QOL-Ostomy) was mailed to each participant. The severity of skin irritation, problems with leakage, and difficulty adjusting were significantly related to demographic, clinical, and quality-of-life domains. Univariate analyses showed that age, income, employment, preoperative care (stoma site marking and education), having a partner, ostomy type, reason for ostomy, time since surgery, total quality-of-life scores and scores on all 4 domains of quality of life were related to the severity of these ostomy complications. Age was inversely related to severity of all 3 ostomy complications (skin irritation, leakage, and difficulty adjusting). Having an ileostomy, rather than a colostomy, was associated with higher severity of skin irritation. Having had the stoma site marked preoperatively was associated with less difficulty adjusting to an ostomy, and having had preoperative ostomy education was associated with less severe problems with skin irritation and leakage. Severity of each ostomy complication predicted total quality-of-life scores. Difficulty adjusting to the ostomy was related to all 4 quality-of-life domains (physical, psychological, social, and spiritual). This study found important relationships between demographic and clinical factors and ostomy complications. Skin problems, leakage, and difficulty adjusting predicted total quality of life scores and domains. Establishing relationships among ostomy complications and demographic, clinical factors, and quality of life can enhance identification of patients at risk for the development of complications and is an important first step in identifying the development of effective interventions to reduce the negative impact of complications for people with ostomies. Further study of predictors and outcomes of ostomy complications is needed to improve care.


Biallelic mutations in BRCA1 cause a new Fanconi anemia subtype.
Deficiency in BRCA-dependent DNA interstrand crosslink (ICL) repair is intimately connected to breast cancer susceptibility and to the rare developmental syndrome Fanconi anemia. Bona fide Fanconi anemia proteins, BRCA2 (FANCD1), PALB2 (FANCN), and BRIP1 (FANCJ), interact with BRCA1 during ICL repair. However, the lack of detailed phenotypic and cellular characterization of a patient with biallelic BRCA1 mutations has precluded assignment of BRCA1 as a definitive Fanconi anemia susceptibility gene. Here, we report the presence of biallelic BRCA1 mutations in a woman with multiple congenital anomalies consistent with a Fanconi anemia-like disorder and breast cancer at age 23. Patient cells exhibited deficiency in BRCA1 and RAD51 localization to DNA-damage sites, combined with radial chromosome formation and hypersensitivity to ICL-inducing agents. Restoration of these functions was achieved by ectopic introduction of a BRCA1 transgene. These observations provide evidence in support of BRCA1 as a new Fanconi anemia gene (FANCS). We establish that biallelic BRCA1 mutations cause a distinct FA-S, which has implications for risk counselling in families where both parents harbor BRCA1 mutations. The genetic basis of hereditary cancer susceptibility syndromes provides diagnostic information, insights into treatment strategies, and more accurate recurrence risk counseling to families.


Body mass index is not a clinically meaningful predictor of patient reported outcomes of primary hip replacement surgery: prospective cohort study.
To describe whether body mass index (BMI) is a clinically meaningful predictor of patient reported outcomes following primary total hip replacement (THR) surgery. Combined data from prospective cohort studies. We obtained information from four cohorts of patients receiving primary THR for osteoarthritis: Exeter Primary Outcomes Study (EPOS) (n = 1431); EUROHIP (n = 1327); Elective Orthopaedic Centre (n = 2832); and St. Helier (n = 787). The exposure of interest was pre-operative BMI. Confounding variables included: age, sex, SF-36 mental health, comorbidities, fixed flexion, analgesic use, college education, OA in other joints, expectation of less pain, radiographic K&L grade, ASA grade, years of hip pain. The primary outcome was the Oxford Hip Score (OHS). Regression models describe the association of BMI on outcome adjusting for all confounders. For a 5-unit increase in BMI, the attained 12-month OHS decreases by 0.78 points 95%CI (0.27-1.28), P-value 0.001. Compared to people of normal BMI (20-25), those in the obese class II (BMI 35-40) would have a 12-month OHS that is 2.34 points lower. Although statistically significant this effect is small and not clinically meaningful in contrast to the substantial change in OHS seen across all BMI groupings. In obese class II patients achieved a 22.2 point change in OHS following surgery. Patients achieved substantial change in OHS after THR across all BMI categories, which greatly outweighs the small difference in attained post-operative score. The findings suggest BMI should not present a barrier to access THR in terms of PROMs.


Digital Pathology and PD-L1 Testing in Non Small Cell Lung Cancer: A Workshop Record.
A meeting among expert pathologists was held in 2019 in Rome to verify the results of the previous harmonization efforts on the PD-L1 immunohistochemical testing by scoring a representative series of non-small cell lung cancer (NSCLC) digital slides. The current paper shows the results of this digital experimental meeting and the expertise achieved by the community of Italian pathologists. PD-L1 protein expression was determined using tumor proportion score (TPS), i.e., the percentage of viable tumor cells showing partial or complete membrane staining at any intensity. The gold standard was defined as the final PD-L1 score formulated by a panel of seven lung committed pathologists. PD-L1 status was clustered in three categories, namely negative (TPS < 1), low (TPS 1-49%), and high (TPS ≥ 50%). In 23 cases (71.9%) PD-L1 staining was performed using the companion diagnostic 22C3 pharmDx kit on Dako Autostainer, while in nine (28.1%) cases it was performed using the SP263 Ventana kit on BenchMark platform. A complete PD-L1 scoring agreement between the panel of experts and the participants was reached in 57.1% of cases, whereas a minor disagreement in 16.1% of cases was recorded. Italian pathologists performed best in strong positive cases (i.e., tumor proportion score TPS > 50%), whereas only 10.8% of disagreement with the gold standard was observed, and 55.6% regarded a single challenging case. The worst performance was achieved in the negative cases, with 32.0% disagreement. A significant difference resulted from the analysis of the data separated by the different clones used: 22.3% and 38.1% disagreement (p = 0.01) was found in the group of cases analyzed by 22C3 and SP263 antibody clones, respectively. In conclusion, this workshop record proposed the application of a digital pathology platform to share controversial cases in educational meetings as an alternative possibility for improving the interpretation and reporting of specific histological tools. Due to the crucial role of PD-L1 TPS for the selection of patients for immunotherapy, the identification of unconventional approaches as virtual slides to focus experiences and give more detailed practical verifications of the standard quality reached may be a considerable option.


Helicobacter infection is required for inflammation and colon cancer in SMAD3-deficient mice.
Accumulating evidence suggests that intestinal microbial organisms may play an important role in triggering and sustaining inflammation in individuals afflicted with inflammatory bowel disease (IBD). Moreover, individuals with IBD are at increased risk for developing colorectal cancer, suggesting that chronic inflammation may initiate genetic or epigenetic changes associated with cancer development. We tested the hypothesis that bacteria may contribute to the development of colon cancer by synergizing with defective transforming growth factor-beta (TGF-beta) signaling, a pathway commonly mutated in human colon cancer. Although others have reported that mice deficient in the TGF-beta signaling molecule SMAD3 develop colon cancer, we found that SMAD3-deficient mice maintained free of the Gram-negative enterohepatic bacteria Helicobacter spp. for up to 9 months do not develop colon cancer. Furthermore, infection of SMAD3(-/-) mice with Helicobacter triggers colon cancer in 50% to 66% of the animals. Using real-time PCR, we found that Helicobacter organisms concentrate in the cecum, the preferred site of tumor development. Mucinous adenocarcinomas develop 5 to 30 weeks after infection and are preceded by an early inflammatory phase, consisting of increased proliferation of epithelial cells; increased numbers of cyclooxygenase-2-positive cells, CD4(+) T cells, macrophages; and increased MHC class II expression. Colonic tissue revealed increased transcripts for the oncogene c-myc and the proinflammatory cytokines interleukin-1alpha (IL-1alpha), IL-1beta, IL-6, IFN-gamma, and tumor necrosis factor-alpha, some of which have been implicated in colon cancer. These results suggest that bacteria may be important in triggering colorectal cancer, notably in the context of gene mutations in the TGF-beta signaling pathway, one of the most commonly affected cellular pathways in colorectal cancer in humans.


Direct demonstration of elevated aldehyde dehydrogenase in human hematopoietic progenitor cells.
Relative levels of cytoplasmic aldehyde dehydrogenase (ALDH) were determined in selected subpopulations of normal human bone marrow cells using a flow cytometric assay that simultaneously detects a cell surface antigen (as a marker of cell lineage and developmental stage) and the level of ALDH. The intracellular level of this enzyme has been shown to be directly related to cellular resistance to activated cyclophosphamide and is believed to be important in the survival of cells capable of repopulating marrow in autologous bone marrow transplant procedures. Western blot analysis and flow cytometric analysis of four murine cell lines with known ALDH levels were used to establish the relation between ALDH content and fluorescence with an affinity-purified anti-mouse ALDH antibody. An affinity purified anti-human ALDH antibody, characterized by immunoblotting of cytosolic extracts of cell lines with known ALDH content, was used to determine relative ALDH levels in the marrow subpopulations. We found that hematopoietic progenitor cells express the highest level of ALDH, while lymphocytes express the lowest level. Immature erythroid cells express ALDH at a level intermediate between progenitor cells and lymphocytes.


Blood-based high sensitivity measurements of beta-amyloid and phosphorylated tau as biomarkers of Alzheimer's disease: a focused review on recent advances.
Discovery and development of clinically useful biomarkers for Alzheimer's disease (AD) and related dementias have been the focus of recent research efforts. While cerebrospinal fluid and positron emission tomography or MRI-based neuroimaging markers have made the in vivo detection of AD pathology and its consequences possible, the high cost and invasiveness have limited their widespread use in the clinical setting. On the other hand, advances in potentially more accessible blood-based biomarkers had been impeded by lack of sensitivity in detecting changes in markers of the hallmarks of AD, including amyloid-β (Aβ) peptides and phosphorylated tau (P-tau). More recently, however, emerging technologies with superior sensitivity and specificity for measuring Aβ and P-tau have reported high concordances with AD severity. In this focused review, we describe several emerging technologies, including immunoprecipitation-mass spectrometry (IP-MS), single molecule array and Meso Scale Discovery immunoassay platforms, and appraise the current literature arising from their use to identify plaques, tangles and other AD-associated pathology. While there is potential clinical utility in adopting these technologies, we also highlight the further studies needed to establish Aβ and P-tau as blood-based biomarkers for AD, including validation with existing large sample sets, new independent cohorts from diverse backgrounds as well as population-based longitudinal studies. In conclusion, the availability of sensitive and reliable measurements of Aβ peptides and P-tau species in blood holds promise for the diagnosis, prognosis and outcome assessments in clinical trials for AD.


Ischemia in tumors induces early and sustained phosphorylation changes in stress kinase pathways but does not affect global protein levels.
Protein abundance and phosphorylation convey important information about pathway activity and molecular pathophysiology in diseases including cancer, providing biological insight, informing drug and diagnostic development, and guiding therapeutic intervention. Analyzed tissues are usually collected without tight regulation or documentation of ischemic time. To evaluate the impact of ischemia, we collected human ovarian tumor and breast cancer xenograft tissue without vascular interruption and performed quantitative proteomics and phosphoproteomics after defined ischemic intervals. Although the global expressed proteome and most of the >25,000 quantified phosphosites were unchanged after 60 min, rapid phosphorylation changes were observed in up to 24% of the phosphoproteome, representing activation of critical cancer pathways related to stress response, transcriptional regulation, and cell death. Both pan-tumor and tissue-specific changes were observed. The demonstrated impact of pre-analytical tissue ischemia on tumor biology mandates caution in interpreting stress-pathway activation in such samples and motivates reexamination of collection protocols for phosphoprotein analysis.


Competitive Self-Assembly Kinetics as a Route To Control the Morphology of Core-Crystalline Cylindrical Micelles.
Nucleated self-assembly in selective solvents of core-crystalline block copolymers (BCPs) is a special case of living supramolecular polymerization, leading to rodlike micelles of controlled and uniform length. For the crystallization-driven self-assembly of PFS-containing BCPs (PFS = polyferrocenyldimethylsilane), the formation of block comicelles by sequential addition of different BCPs is well-established. But there are only a few examples of living copolymerization, the simultaneous addition of pairs of BCPs with different corona-forming chains. At present, relatively little is known about the competitive kinetics of different BCPs crystallizing on a common seed. Here we report a systematic study of the competitive seeded growth kinetics of pairs of linear PFS-containing BCPs and show that one can manipulate the kinetics to control the morphology of the comicelles. We found that the seeded-growth kinetics of the individual BCP unimer dominates the coassembly behavior and thus the morphology of the corona. Patchy comicelles with microphase-segregated corona chains are formed when the epitaxial growth rates of the two different BCPs on the common seed are similar. In contrast, factors that lead to dissimilar growth rates (long corona-forming blocks or introduction of charges on corona-forming chains) promote large-scale separation of the corona blocks, leading to block comicelles. Because the termini of the comicelles remain living, they can further direct the growth of unimers, resulting in hierarchical block comicelles with patchy blocks and single-component (homo) blocks. Furthermore, the patchy comicelles can be loaded with either gold or platinum nanoparticles, generating organic-inorganic hybrid materials with potential application in catalysis.


Peer victimization during adolescence: concurrent and prospective impact on symptoms of depression and anxiety.
Peer victimization is ubiquitous across schools and cultures, and has the potential for long-lasting effects on the well-being of victims. To date, research has focused on the consequences of peer victimization during childhood but neglected adolescence. Peer relationships and approval become increasingly important during adolescence; thus, peer victimization at this age may have a damaging psychological impact. Participants were 5030 adolescents aged 11-16 recruited from secondary schools in the UK. Self-report measures of victimization and symptoms of anxiety and depression were administered on three occasions over a 12-month period. Latent growth models examined concurrent and prospective victimization-related elevations in anxiety and depression symptoms above individual-specific growth trajectories. Peer victimization was associated with a concurrent elevation of 0.64 and 0.56 standard deviations in depression and anxiety scores, respectively. There was an independent delayed effect, with additional elevations in depression and anxiety (0.28 and 0.25 standard deviations) six months later. These concurrent and prospective associations were independent of expected symptom trajectories informed by individual risk factors. Adolescent peer victimization was associated with immediate and delayed elevations in anxiety and depression. Early intervention aimed at identifying and supporting victimized adolescents may prevent the development of these disorders.


Molecular replication using covalent base-pairs with traceless linkers.
A unique feature of kinetically inert covalent base-pairing is that the nature of the chemical information that is transferred can be modulated by changing the chemical connectivity between the two bases. Formation of esters between phenols and benzoic acids has been used as a base-pairing strategy for sequence information transfer in template-directed synthesis of linear oligomers, but the copy strand produced by this process has the complementary sequence to the template strand. It is possible to form a base-pair between two benzoic acids by using a hydroquinone linker, which is eliminated when the product duplex is hydrolysed. Using this approach, covalent template-directed synthesis was carried out using a benzoic acid 3-mer template to produce an identical copy. This direct replication process was used in iterative rounds of replication leading to an increase of the population of the copied oligomer.


Predictive genomics DNA profiling for athletic performance.
Genes control biological processes such as muscle, cartilage and bone formation, muscle energy production and metabolism (mitochondriogenesis, lactic acid removal), blood and tissue oxygenation (erythropoiesis, angiogenesis, vasodilatation), all essential in sport and athletic performance. DNA sequence variations in such genes confer genetic advantages that can be exploited, or genetic 'barriers' that could be overcome to achieve optimal athletic performance. Predictive Genomic DNA Profiling for athletic performance reveals genetic variations that may be associated with better suitability for endurance, strength and speed sports, vulnerability to sports-related injuries and individualized nutritional requirements. Knowledge of genetic 'suitability' in respect to endurance capacity or strength and speed would lead to appropriate sport and athletic activity selection. Knowledge of genetic advantages and barriers would 'direct' an individualized training program, nutritional plan and nutritional supplementation to achieving optimal performance, overcoming 'barriers' that results from intense exercise and pressure under competition with minimum waste of time and energy and avoidance of health risks (hypertension, cardiovascular disease, inflammation, and musculoskeletal injuries) related to exercise, training and competition. Predictive Genomics DNA profiling for Athletics and Sports performance is developing into a tool for athletic activity and sport selection and for the formulation of individualized and personalized training and nutritional programs to optimize health and performance for the athlete. Human DNA sequences are patentable in some countries, while in others DNA testing methodologies [unless proprietary], are non patentable. On the other hand, gene and variant selection, genotype interpretation and the risk and suitability assigning algorithms based on the specific Genomic variants used are amenable to patent protection.


Translation and cultural adaptation into Spanish of the Low Vision Quality of Life Questionnaire.
The purpose of the present study was to provide a translation into Spanish, as well as a cross-cultural adaptation, of the English version of the Low Vision Quality of Life Questionnaire (LVQOL). There are currently some questionnaires designed to assess vision related quality of life in Spanish, although none of them specifically examines the quality of life of patients with visual disability. The LVQOL consists of 25 items and examines 4 different dimensions: distance vision; mobility and ilumination; adaptation, reading and precision work, and daily life activities. The process of translation and cross-cultural adaptation was conducted following the recommendations of the International Society for Pharmacoeconomics and Outcomes. This included, amongst other variables, a direct translation, a back-translation, and a cognitive debriefing with a small sample of patients with visual impairment. Work was supervised by an expert committee consisting of an ophthalmologist, a psychologist with expertise in Patient Reported Outcomes, and an optician-optometrist with experience in the field of low vision. A total of 46 phrases were considered for translation of which, 41 (89.1%) had excellent equivalence, 3 (6.5%) moderate equivalence, and 2 poor equivalence. The cognitive debriefing phase showed a high degree of acceptance of the questionnaire by the sample of participants with visual impairment. The results obtained suggest that the Spanish version of this tool is understandable for patients with visual impairment. Its properties as a measuring tool will be evaluated in a later study to determine its validity, reliability, and sensitivity to changes.


Long-term health care utilisation and costs after spinal fusion in elderly patients.
Spinal fusion surgery rates in the elderly are increasing. Cost effectiveness analyses with relatively short-length follow-up have been performed. But the long-term effects in terms of health care use are largely unknown. The aim of the present study was to describe the long-term consequences of spinal fusion surgery in elderly patients on health care use and costs using a health care system perspective. 194 patients undergoing spinal fusion between 2001 and 2005 (70 men, 124 women) with a mean age of 70 years (range 59-88) at surgery were included. Average length of follow-up was 6.2 years (range 0.3-9.0 years). Data on resource utilisation and costs were obtained from national registers providing complete coverage of all reimbursed contacts with primary- and secondary health care providers. Data were available from 3 years prior fusion surgery until the end of 2009. Use of hospital-based health care increased in the year prior to and the first year following surgery. Hereafter it normalised to the level of the background population and was mainly composed of diseases unrelated to the spine. In contrast, the use of primary health care appeared to increase immediately after surgery and continued to increase to a level that significantly exceeded that of the background population. It could be demonstrated that the increase was mainly due to an increasing number of general practitioner consultations. Spinal fusion surgery in older patients does not generate excess hospital-based health care use in the longer term as compared with the background population, but primary care use increases.


Comparison of phototherapy (UV-B) and photochemotherapy (PUVA) for clearing and maintenance therapy of psoriasis.
One hundred eighty-three patients with psoriasis were treated with UV-B irradiation or oral methoxsalen plus longwave UV light (PUVA). Patients treated with PUVA, in the initial and maintenance period, achieved in general a higher therapeutic score (95% to 100% clearance) than those receiving UV-B therapy. However, taking 80% to 100% improvement as criterion, no difference was found between initial UV-B and PUVA therapy, if less than 50% of the skin surface was affected by psoriasis. If more than 50% of the skin was involved, PUVA was better than UV-B therapy. The maintenance treatment frequency for the UV-B-treated patients for more than a year seemed to be higher than for PUVA-treated patients. A positive correlation was found between response to sunbathing (questionnaire survey) and the response to UV-B phototherapy. An extra UV-B treatment to the leg lesions appeared useless.


Correlation between histidine operon expression and guanosine 5'-diphosphate-3'-diphosphate levels during amino acid downshift in stringent and relaxed strains of Salmonella typhimurium.
We have analyzed the correlation of attenuator-independent expression of the Salmonella typhimurium histidine operon in vivo with levels of the "alarmone" guanosine 5'-diphosphate 3'-diphosphate. Amino acid downshift caused by serine hydroxamate addition increased his expression in a relA+ strain and decreased his expression in a relA mutant, whereas levels of guanosine 5'-diphosphate-3'-diphosphate varied in parallel with the changes in his expression in the two strains. In several experiments, overall variations in his expression ranged from 20- to 60-fold after downshift. The mild downshift allowed growth of the cultures to continue at near-preshift rates. Serine hydroxamate addition was also used to analyze the effect of amino acid downshift on induced expression of wild-type and mutant lac promoters. There was a 12-fold difference in lac expression when a relA+-relA1 pair was subjected to mild starvation but only a 3-fold difference when the strains carried the lacZpL8UV5 promoter mutation. These results suggest that guanosine 5'-diphosphate-3'-diphosphate stimulates gene expression in vivo at the level of transcription initiation.


Hearing loss in stranded odontocete dolphins and whales.
The causes of dolphin and whale stranding can often be difficult to determine. Because toothed whales rely on echolocation for orientation and feeding, hearing deficits could lead to stranding. We report on the results of auditory evoked potential measurements from eight species of odontocete cetaceans that were found stranded or severely entangled in fishing gear during the period 2004 through 2009. Approximately 57% of the bottlenose dolphins and 36% of the rough-toothed dolphins had significant hearing deficits with a reduction in sensitivity equivalent to severe (70-90 dB) or profound (>90 dB) hearing loss in humans. The only stranded short-finned pilot whale examined had profound hearing loss. No impairments were detected in seven Risso's dolphins from three different stranding events, two pygmy killer whales, one Atlantic spotted dolphin, one spinner dolphin, or a juvenile Gervais' beaked whale. Hearing impairment could play a significant role in some cetacean stranding events, and the hearing of all cetaceans in rehabilitation should be tested.


Aortic Hemostasis and Resuscitation: Preliminary Experiments Using Selective Aortic Arch Perfusion With Oxygenated Blood and Intra-aortic Calcium Coadministration in a Model of Hemorrhage-induced Traumatic Cardiac Arrest.
Selective aortic arch perfusion (SAAP) uses a thoracic aortic balloon occlusion catheter for heart and brain perfusion in cardiac arrest to achieve return of spontaneous circulation (ROSC). SAAP with oxygenated stored blood was studied in a model of hemorrhage-induced cardiac arrest. The study hypothesis was that intra-aortic calcium coadministration would be required to maintain normal aortic arch blood ionized calcium during SAAP and to achieve ROSC. Twelve anesthetized, domestic swine underwent severe hemorrhage and liver injury resulting in cardiac arrest. Whole blood and packed red blood cells (RBCs) stored in citrate anticoagulant served as perfusates for SAAP. Experiments were performed with four combinations of SAAP with oxygenated stored blood and intra-aortic calcium gluconate infusion: 1) whole blood without calcium, 2) whole blood with calcium, 3) lactated Ringers-diluted packed RBCs with calcium, and 4) normal saline-diluted packed RBCs with calcium. Aortic arch blood ionized calcium was monitored. Occurrence of ventricular dysrhythmias, success rate for ROSC, and the need for simultaneous intra-aortic calcium infusion were assessed. Selective aortic arch perfusion using whole blood without intra-aortic calcium (n = 2) resulted in severe aortic blood ionized hypocalcemia, refractory ventricular fibrillation, and no ROSC. SAAP using whole blood with intra-aortic calcium (n = 4) resulted in ROSC in all four animals. Two of four developed ventricular fibrillation that was successfully defibrillated. SAAP using packed RBCs with intra-aortic calcium resulted in ROSC in all six animals, but the intra-aortic calcium dose needed to maintain normal aortic arch blood ionized calcium levels was one-third of that needed for SAAP with whole blood. Dilution of packed RBCs with lactated Ringers (n = 2) resulted in formation of small clots in the perfusion circuit which were not seen with packed RBCs diluted with normal saline (n = 4). Selective aortic arch perfusion with stored whole blood or packed RBCs requires simultaneous intra-aortic calcium infusion to overcome citrate anticoagulant calcium binding, avoid refractory ventricular fibrillation, and allow for ROSC.


Mechanism of inhibition of DNA (cytosine C5)-methyltransferases by oligodeoxyribonucleotides containing 5,6-dihydro-5-azacytosine.
A key step in the predicted mechanism of enzymatic transfer of methyl groups from S-adenosyl-l-methionine (AdoMet) to cytosine residues in DNA is the transient formation of a dihydrocytosine intermediate covalently linked to cysteine in the active site of a DNA (cytosine C5)-methyltransferase (DNA C5-MTase). Crystallographic analysis of complexes formed by HhaI methyltransferase (M.HhaI), AdoMet and a target oligodeoxyribonucleotide containing 5-fluorocytosine confirmed the existence of this dihydrocytosine intermediate. Based on the premise that 5,6-dihydro-5-azacytosine (DZCyt), a cytosine analog with an sp3-hybridized carbon (CH2) at position 6 and an NH group at position 5, could mimic the non-aromatic character of the cytosine ring in this transition state, we synthesized a series of synthetic substrates for DNA C5-MTase containing DZCyt. Substitution of DZCyt for target cytosines in C-G dinucleotides of single-stranded or double-stranded oligodeoxyribonucleotide substrates led to complete inhibition of methylation by murine DNA C5-MTase. Substitution of DZCyt for the target cytosine in G-C-G-C sites in double-stranded oligodeoxyribonucleotides had a similar effect on methylation by M. HhaI. Oligodeoxyribonucleotides containing DZCyt formed a tight but reversible complex with M.HhaI, and were consistently more potent as inhibitors of DNA methylation than oligodeoxyribonucleotides identical in sequence containing 5-fluorocytosine. Crystallographic analysis of a ternary complex involving M.HhaI, S-adenosyl-l-homocysteine and a double-stranded 13-mer oligodeoxyribonucleotide containing DZCyt at the target position showed that the analog is flipped out of the DNA helix in the same manner as cytosine, 5-methylcytosine, and 5-fluorocytosine. However, no formation of a covalent bond was detected between the sulfur atom of the catalytic site nucleophile, cysteine 81, and the pyrimidine C6 carbon. These results indicate that DZCyt can occupy the active site of M.HhaI as a transition state mimic and, because of the high degree of affinity of its interaction with the enzyme, it can act as a potent inhibitor of methylation.


Towards Distributed Recycling with Additive Manufacturing of PET Flake Feedstocks.
This study explores the potential to reach a circular economy for post-consumer Recycled Polyethylene Terephthalate (rPET) packaging and bottles by using it as a Distributed Recycling for Additive Manufacturing (DRAM) feedstock. Specifically, for the first time, rPET water bottle flake is processed using only an open source toolchain with Fused Particle Fabrication (FPF) or Fused Granular Fabrication (FGF) processing rather than first converting it to filament. In this study, first the impact of granulation, sifting, and heating (and their sequential combination) is quantified on the shape and size distribution of the rPET flakes. Then 3D printing tests were performed on the rPET flake with two different feed systems: an external feeder and feed tube augmented with a motorized auger screw, and an extruder-mounted hopper that enables direct 3D printing. Two Gigabot X machines were used, each with the different feed systems, and one without and the latter with extended part cooling. 3D print settings were optimized based on thermal characterization, and both systems were shown to 3D print rPET directly from shredded water bottles. Mechanical testing showed the importance of isolating rPET from moisture and that geometry was important for uniform extrusion. The mechanical strength of 3D-printed parts with FPF and inconsistent flow is lower than optimized fused filament, but adequate for a wide range of applications. Future work is needed to improve consistency and enable water bottles to be used as a widespread DRAM feedstock.


Use of the Gail model and breast cancer preventive therapy among three primary care specialties.
Breast cancer is an issue of serious concern among women of all ages. The extent to which providers across primary care specialties assess breast cancer risk and discuss chemoprevention is unknown. Cross-sectional web-based survey completed by 316 physicians in internal medicine (IM), family medicine (FM), and gynecology (GYN) from February to April of 2012. Survey items assessed respondents' frequency of use of the Gail model and chemoprevention, and their attitudes behind practice patterns. Descriptive statistics were used to generate response distributions, and chi-squared tests were used to compare responses among specialties. The response rate was 55.0 % (316/575). Only 40% of providers report having used the Gail model (37% IM, 33% FM, 60% GYN) and 13% report having recommended or prescribed chemoprevention (9% IM, 8% FM, 30% GYN). Among providers who use the Gail model, a minority use it regularly in patients who may be at increased breast cancer risk. Among providers who have prescribed chemoprevention, most have done so five times or fewer. Lack of both time and familiarity were commonly cited barriers to use of the Gail score and chemoprevention. An overall minority of providers, most notably in FM and IM, use the Gail model to assess, and chemoprevention to decrease, breast cancer risk. Until providers are more consistent in their use of the Gail model (or other breast cancer risk calculator) and chemoprevention, opportunities to intervene in women at increased risk will likely continue to be missed.


Activity in the paracingulate and cingulate sulci during word generation: an fMRI study of functional anatomy.
The supracallosal medial frontal cortex can be divided into three functional domains: a ventral region with connections to the limbic system, an anterior dorsal region with connections to lateral prefrontal systems, and a posterior dorsal region with connections to lateral motor systems. Lesion and functional imaging studies implicate this medial frontal cortex in speech and language generation. The current functional magnetic resonance imaging (fMRI) study of word generation was designed to determine which of these three functional domains was substantially involved by mapping individual subjects' functional activity onto structural images of their left medial frontal cortex. Of 28 neurologically normal right-handed participants, 21 demonstrated a prominent paracingu- late sulcus (PCS), which lies in the anterior dorsal region with connections to lateral prefrontal systems. Activity increases for word generation centered in the PCS in 18 of these 21 cases. The posterior dorsal region also demonstrated significant activity in a majority of participants (16/28 cases). Activity rarely extended into the cingulate sulcus (CS) (3/21 cases) when there was a prominent PCS. If there was no prominent PCS, however, activity did extend into the CS (6/7 cases). In no case was activity present on the crest of the cingulate gyrus, which is heavily connected to the limbic system. Thus, current findings suggest that medial frontal activity during word generation reflects cognitive and motor rather than limbic system participation. The current study demonstrates that suitably designed fMRI studies can be used to determine the functional significance of anatomic variants in human cortex.


Short-term responses to warming vary between native vs. exotic species and with latitude in an early successional plant community.
Climate change is expected to favor exotic plant species over native species, because exotics tend to have wider climatic tolerances and greater phenological plasticity, and also because climate change may intensify enemy release. Here, we examine direct effects of warming (+ 1.8 °C above ambient) on plant abundance and phenology, as well as indirect effects of warming propagated through herbivores, in two heavily invaded plant communities in Michigan, USA, separated by approximately three degrees latitude. At the northern site, warming increased exotic plant abundance by 19% but decreased native plant abundance by 31%, indicating that exotic species may be favored in a warmer world. Warming also resulted in earlier spring green-up (1.65 ± 0.77 days), earlier flowering (2.18 ± 0.92 days), and greater damage by herbivores (twofold increase), affecting exotic and native species equally. Contrary to expectations, native and exotic plants experienced similar amounts of herbivory. Warming did not have strong ecological effects at the southern site, only resulting in a delay of flowering time by 2.42 ± 0.83 days for both native and exotic species. Consistent with the enemy release hypothesis, exotic plants experienced less herbivory than native plants at the southern site. Herbivory was lower under warming for both exotic and native species at the southern site. Thus, climate warming may favor exotic over native plant species, but the response is likely to depend on additional environmental and individual species' traits.


Prolonged sleep duration as a marker of early neurodegeneration predicting incident dementia.
To evaluate the association between sleep duration and the risk of incident dementia and brain aging. Self-reported total hours of sleep were examined in the Framingham Heart Study (n = 2,457, mean age 72 ± 6 years, 57% women) as a 3-level variable: <6 hours (short), 6-9 hours (reference), and >9 hours (long), and was related to the risk of incident dementia over 10 years, and cross-sectionally to total cerebral brain volume (TCBV) and cognitive performance. We observed 234 cases of all-cause dementia over 10 years of follow-up. In multivariable analyses, prolonged sleep duration was associated with an increased risk of incident dementia (hazard ratio [HR] 2.01; 95% confidence interval [CI] 1.24-3.26). These findings were driven by persons with baseline mild cognitive impairment (HR 2.83; 95% CI 1.06-7.55) and persons without a high school degree (HR 6.05; 95% CI 3.00-12.18). Transitioning to sleeping >9 hours over a mean period of 13 years before baseline was associated with an increased risk of all-cause dementia (HR 2.43; 95% CI 1.44-4.11) and clinical Alzheimer disease (HR 2.20; 95% CI 1.17-4.13). Relative to sleeping 6-9 hours, long sleep duration was also associated cross-sectionally with smaller TCBV (β ± SE, -1.08 ± 0.41 mean units of TCBV difference) and poorer executive function (β ± SE, -0.41 ± 0.13 SD units of Trail Making Test B minus A score difference). Prolonged sleep duration may be a marker of early neurodegeneration and hence a useful clinical tool to identify those at a higher risk of progressing to clinical dementia within 10 years.


Application of Multiscale Entropy in Assessing Plantar Skin Blood Flow Dynamics in Diabetics with Peripheral Neuropathy.
Diabetic foot ulcer (DFU) is a common complication of diabetes mellitus, while tissue ischemia caused by impaired vasodilatory response to plantar pressure is thought to be a major factor of the development of DFUs, which has been assessed using various measures of skin blood flow (SBF) in the time or frequency domain. These measures, however, are incapable of characterizing nonlinear dynamics of SBF, which is an indicator of pathologic alterations of microcirculation in the diabetic foot. This study recruited 18 type 2 diabetics with peripheral neuropathy and eight healthy controls. SBF at the first metatarsal head in response to locally applied pressure and heating was measured using laser Doppler flowmetry. A multiscale entropy algorithm was utilized to quantify the regularity degree of the SBF responses. The results showed that during reactive hyperemia and thermally induced biphasic response, the regularity degree of SBF in diabetics underwent only small changes compared to baseline and significantly differed from that in controls at multiple scales (p < 0.05). On the other hand, the transition of regularity degree of SBF in diabetics distinctively differed from that in controls (p < 0.05). These findings indicated that multiscale entropy could provide a more comprehensive assessment of impaired microvascular reactivity in the diabetic foot compared to other entropy measures based on only a single scale, which strengthens the use of plantar SBF dynamics to assess the risk for DFU.


A standard protocol for single nucleotide primer extension in the human genome using matrix-assisted laser desorption/ionization time-of-flight mass spectrometry.
Analysis of single nucleotide polymorphisms (SNPs) has become an increasingly important area of research, with numerous applications in medical genetics, population genetics, forensic science, and agricultural biotechnology. Large-scale SNP analyses require the development of methodologies that are economical, flexible, accurate and capable of automation. Primer extension in conjunction with matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOFMS) is currently emerging as a potential method for high-throughput SNP genotyping. We have evaluated a number of published primer extension methods and refined a simple and robust protocol to analyze human autosomal disease-causing mutations and population genetic markers on the Y-chromosome. Twelve different variant sites were examined, and homozygotes, heterozygotes and hemizygotes were accurately typed. A 100% concordance was observed between SNP genotypes obtained using the MALDI-TOFMS technique and alternative genotyping methods, such as restriction fragment length polymorphism (RFLP) assays and denaturing high-performance liquid chromatography (DHPLC). Since multiple polymorphisms can be detected in single reactions, the method provides a cost-effective approach for SNP analysis. The protocol is also extremely flexible (able to accommodate new markers) and can be adapted to a number of platforms without the use of commercial kits.


Pretargeting in nuclear imaging and radionuclide therapy: Improving efficacy of theranostics and nanomedicines.
Pretargeted nuclear imaging and radiotherapy have recently attracted increasing attention for diagnosis and treatment of cancer with nanomedicines. This is because it conceptually offers better imaging contrast and therapeutic efficiency while reducing the dose to radiosensitive tissues compared to conventional strategies. In conventional imaging and radiotherapy, a directly radiolabeled nano-sized vector is administered and allowed to accumulate in the tumor, typically on a timescale of several days. In contrast, pretargeting is based on a two-step approach. First, a tumor-accumulating vector carrying a tag is administered followed by injection of a fast clearing radiolabeled agent that rapidly recognizes the tag of the tumor-bound vector in vivo. Therefore, pretargeting circumvents the use of long-lived radionuclides that is a necessity for sufficient tumor accumulation and target-to-background ratios using conventional approaches. In this review, we give an overview of recent advances in pretargeted imaging strategies. We will critically reflect on the advantages and disadvantages of current state-of-the-art conventional imaging approaches and compare them to pretargeted strategies. We will discuss the pretargeted imaging concept and the involved chemistry. Finally, we will discuss the steps forward in respect to clinical translation, and how pretargeted strategies could be applied to improve state-of-the-art radiotherapeutic approaches.


Separate adaptive mechanisms for controlling trajectory and final position in reaching.
We examined control of the hand's trajectory (direction and shape) and final equilibrium position in horizontal planar arm movements by quantifying transfer of learned visuomotor rotations between two tasks that required aiming the hand to the same spatial targets. In a trajectory-reversal task ("slicing"), the hand reversed direction within the target and returned to the origin. In a positioning task ("reaching"), subjects moved the hand to the target and held it there; cursor feedback was provided only after movement ended to isolate learning of final position from trajectory direction. We asked whether learning acquired in one task would transfer to the other. Transfer would suggest that the hand's entire trajectory, including its endpoint, was controlled using a common spatial plan. Instead we found minimal transfer, suggesting that the brain used different representations of target position to specify the hand's initial trajectory and its final stabilized position. We also observed asymmetrical practice effects on hand trajectory, including systematic curvature of reaches made after rotation training and hypermetria of untrained slice reversals after reach training. These are difficult to explain with a unified control model, but were replicated in computer simulations that specified the hand's initial trajectory and its final equilibrium position. Our results suggest that the brain uses different mechanisms to plan the hand's initial trajectory and final position in point-to-point movements, that it implements these control actions sequentially, and that trajectory planning does not account for specific impedance values to be implemented about the final stabilized posture.


rCUR: an R package for CUR matrix decomposition.
Many methods for dimensionality reduction of large data sets such as those generated in microarray studies boil down to the Singular Value Decomposition (SVD). Although singular vectors associated with the largest singular values have strong optimality properties and can often be quite useful as a tool to summarize the data, they are linear combinations of up to all of the data points, and thus it is typically quite hard to interpret those vectors in terms of the application domain from which the data are drawn. Recently, an alternative dimensionality reduction paradigm, CUR matrix decompositions, has been proposed to address this problem and has been applied to genetic and internet data. CUR decompositions are low-rank matrix decompositions that are explicitly expressed in terms of a small number of actual columns and/or actual rows of the data matrix. Since they are constructed from actual data elements, CUR decompositions are interpretable by practitioners of the field from which the data are drawn. We present an implementation to perform CUR matrix decompositions, in the form of a freely available, open source R-package called rCUR. This package will help users to perform CUR-based analysis on large-scale data, such as those obtained from different high-throughput technologies, in an interactive and exploratory manner. We show two examples that illustrate how CUR-based techniques make it possible to reduce significantly the number of probes, while at the same time maintaining major trends in data and keeping the same classification accuracy. The package rCUR provides functions for the users to perform CUR-based matrix decompositions in the R environment. In gene expression studies, it gives an additional way of analysis of differential expression and discriminant gene selection based on the use of statistical leverage scores. These scores, which have been used historically in diagnostic regression analysis to identify outliers, can be used by rCUR to identify the most informative data points with respect to which to express the remaining data points.


Efficacy of manual and powered toothbrushes (I). Effect on clinical parameters.
The purpose of the present investigation was to compare manual (Crest Complete) and powered toothbrushing (Braun Oral-B 3D Plaque Remover) for their ability to affect clinical parameters of periodontal diseases. 48 periodontal maintenance subjects completed this single-blind 6-month longitudinal study. Subjects had a minimum of 20 natural teeth excluding third molars and >10% of sites (approximately 17 sites) with pocket depth > or =4 mm and/or >10% sites with attachment level >4 mm. At baseline, subjects received full mouth clinical measurements (168 sites) to determine mean Plaque Index, Gingival Index, pocket depth and attachment level and % of sites exhibiting BOP. Subjects were then randomly assigned to one of two groups. The control group (N=26) used a manual toothbrush while the test group (N=22) used a powered toothbrush. Subjects received instruction in oral hygiene and used their assigned toothbrush twice daily according to instruction. Follow-up clinical assessments were performed at 3 and 6 months. Significance of differences in clinical measures over time was determined using the Quade test and between brushing groups at each time point using the Mann-Whitney test. Mean pocket depth, mean plaque index and % of sites exhibiting BOP showed significant reductions from baseline to 3 and 6 months in both groups. Mean probing attachment level and mean Gingival Index were significantly reduced in the powered brushing group only. There was a significant positive correlation between plaque reduction and reduction in other clinical parameters in both brushing groups. The majority of subjects showed improvements in clinical parameters at 6 months, although a greater proportion of subjects in the powered group showed a reduction in Plaque Index (77% versus 65%) and in % sites exhibiting BOP (82% versus 69%). Mean pocket depth and mean attachment level showed significantly greater reductions between baseline and 6 months in lingual and mandibular areas in the powered group. Both manual and powered toothbrushes reduced pocket depth, plaque index and BOP. The powered toothbrush significantly reduced mean gingival index and probing attachment level. The greatest benefit of the powered brush was at mandibular and lingual surfaces.


[Surgical treatment for Parkinson's disease].
In the past years there has been an increasing interest in the surgical therapies for Parkinson's disease. This renewed interest is related to differents factors. First, pharmacological treatments are still unable to alter substantially the progression of the disease and after a few years they generally cause motor complications and dyskinesias. Secondly, the great advances in the surgical techniques, especially with the improvement of stereotactic surgery, have decreased morbidity in recent years. Finally, the introduction of deep brain stimulation, now allows surgical treatment without damaging brain structures. In this review, different surgical treatments are summarized. Ablative surgery, deep brain stimulation and reinervation therapies are described.


Evaluating the Effect of Surgical Skill on Outcomes for Laparoscopic Sleeve Gastrectomy: A Video-based Study.
Prior studies have demonstrated a correlation between surgical skill and complication rates after laparoscopic Roux-en-Y gastric bypass. However, the impact of surgical skill on a similar but less technically challenging procedure such as sleeve gastrectomy (SG) is unknown. Practicing bariatric surgeons (n = 25) participating in a statewide quality improvement collaborative submitted an unedited deidentified video of a representative laparoscopic SG. Videos were obtained between 2015 and 2016 and were rated by bariatric surgeons in a blinded fashion using a validated instrument that assesses surgical skill. Overall scores were based on a 5-point Likert scale with 5 representing a "master surgeon" and 1 representing a "surgeon-in-training." Risk-adjusted 30-day complication rates, 1-year weight loss among cases performed during the study period, and operative technique were compared between surgeons rated in the top and bottom quartiles according to skill. Surgeon ratings for skill varied between 2.73 and 4.60. Ratings for skill did not correlate with overall 30-day risk-adjusted complication rates (Pearson correlation coefficient, 0.213, P = 0.303). However, surgeons with higher skill ratings had lower rates of specific surgical complications, including postoperative obstruction (0.13% vs 0.3%, P = 0.017), hemorrhage (0.85% vs 1.27%, P = 0.005), and reoperation (0.24% vs 0.92%, P < 0.0001). Surgeons ranked in the top quartile for skill had faster operating times for SG (59.0 vs 82.1 min, P < 0.0001) and higher annual case volumes for both SG and any bariatric procedure (224.3 cases/yr vs 73.4 cases/yr, P = 0.009 and 244.9 cases/yr and 93.9 cases/yr, P = 0.009) when compared with surgeons in the bottom quartile. When comparing operative technique, top rated surgeons were noted to have a higher likelihood of using buttressing (83.3% vs 0%, P = 0.0041) and intraoperative endoscopy (83.3% vs 0%, P = 0.0041). Peer ratings for surgical skill varied for laparoscopic sleeve gastrectomy but did not have a significant impact on overall complication rates. Top rated surgeons had lower rates of obstruction, hemorrhage, and reoperation; however, severe morbidity remained extremely low among all surgeons.


Assessment of Patients with Intracerebral Hemorrhage or Hemorrhagic Transformation in the VENOST Study.
Cerebral venous and sinus thrombosis (CVST) may lead to cerebral edema and increased intracranial pressure; besides, ischemic or hemorrhagic lesions may develop. Intracerebral hemorrhages occur in approximately one-third of CVST patients. We assessed and compared the findings of the cerebral hemorrhage (CH) group and the CVST group. In the VENOST study, medical records of 1,193 patients with CVST, aged over 18 years, were obtained from 35 national stroke centers. Demographic characteristics, clinical symptoms, signs at the admission, radiological findings, etiologic factors, acute and maintenance treatment, and outcome results were reported. The number of involved sinuses or veins, localizations of thrombus, and lesions on CT and MRI scans were recorded. CH was detected in the brain imaging of 241 (21.1%) patients, as hemorrhagic infarction in 198 patients and intracerebral hemorrhage in 43 patients. Gynecologic causes comprised the largest percentage (41.7%) of etiology and risk factors in the CVST group. In the CH group, headache associated with other neurological symptoms was more frequent. These neurological symptoms were epileptic seizures (46.9%), nausea and/or vomiting (36.5%), altered consciousness (36.5%), and focal neurological deficits (33.6%). mRS was ≥3 in 23.1% of the patients in the CH group. CVST, an important cause of stroke in the young, should be monitored closely if the patients have additional symptoms of headache, multiple sinus involvement, and CH. Older age and parenchymal lesion, either hemorrhagic infarction or intracerebral hemorrhage, imply poor outcome.


Pattern and outcome of vascular involvement of Omani patients with Behcet's disease.
The objective of the study is to study the pattern, frequency and outcome of vascular events in Omani patients with Behcet's disease (BD). Forty BD patients were recruited. Clinical data parameters were recorded, including age at onset, disease duration, current disease activity, and the vascular manifestations of the disease (current and past events). Disease activity was assessed by ESR, CRP and also clinically. For venous and arterial thrombotic events, imaging studies, such as Doppler ultrasonography, angiography, MRI, CT, and echocardiography were performed. Nine patients had vascular events (23%). The mean age of these patients at diagnosis of the vascular event was 24 years (range 15-37) and the mean disease duration at onset of the vascular event was 3.8 years (range 3-5); this was significant when compared with patients without thrombosis (P=0.001, Mann-Whitney test). In these patients with vascular involvement, two patients (22%) had venous lesions, three (33%) patients had arterial lesions and four patients (44%) had mixed lesions. Two patients (22%) had pulmonary artery aneurysm (PAA) and concomitant intracardiac thrombus, and further one patient also had PAA. Immunosuppressive therapy resulted in the resolution of PAA and intracardiac thrombous. In conclusion, the frequency of vascular complications of BD in our patients is similar to those reported around the world. We found younger male patients with short disease duration are at a greater risk of developing thrombosis. Medical treatment with immunosuppressive therapy without anticoagulation seems successful in treating PAA and intracardiac thrombus.


Reviving informed consent: using risk perception in clinical trials.
The current doctrine of informed consent falls far short of its potential to serve as a valuable safeguard for human research subjects. Instead of providing a channel of communication between physician and subject, informed consent is a lifeless entity responsible for a large portion of the misunderstanding existing between these parties. Acknowledging risk perception principles may help transform the informed consent process into an effective communication of health risks.


Blood oxygenation level dependent contrast resting state networks are relevant to functional activity in the neocortical sensorimotor system.
The relevance of correlations between blood oxygenation level dependent (BOLD) signal changes across the brain acquired at rest (resting state networks, or RSN) to functional networks was tested using two quantitative criteria: (1) the localisation of major RSN correlation clusters and the task-related maxima defined in BOLD fMRI signal changes from the same subjects; and (2) the relative hemispheric lateralisation (LI) of BOLD fMRI signal changes in sensorimotor cortex. RSN were defined on the basis of signal changes correlated with that of a "seed" voxel in the primary sensorimotor cortex. We found a generally close spatial correspondence between clusters of correlated BOLD signal change in RSN and activation maxima associated with hand movement. Conventional BOLD fMRI during active hand movement showed the expected wide variation in relative hemispheric lateralisation of LI for sensorimotor cortex across the subjects. There was a good correlation between LIs for the active hand movement task and the RSN (r=0.74, p<0.001). The RSN thus define anatomically relevant regions of motor cortex and change with functionally relevant variations in hemispheric lateralisation of sensorimotor cortical interactions with hand movement.


Adenosine 5'-triphosphate-sensitive potassium channels.
This review has focused on the properties of the ATP-sensitive K-channel found in cardiac and skeletal muscle, and in pancreatic beta-cells. It is conceivable that this channel will be found in other cell types. In particular, it would be worthwhile looking for its presence in those cells in which electrical activity is linked to metabolism, glucose concentration, or oxygen levels. Obvious examples are the glucoreceptor neurons of mammalian brain and chemoreceptors such as those of the carotid body. While ATP-sensitive K-channels in cardiac and skeletal muscle membranes are rather similar, there are a few significant differences between these channels and that found in the beta-cell. Most notably, the latter is more sensitive to inhibition by ATP and sulphonylureas. It remains to be seen whether they also differ in the ability of nucleotides to activate the channel. Considerable confusion also still surrounds the physiological regulation of the ATP-sensitive K-channel in intact cells. Although the general consensus seems to be that [ATP]i modulates channel activity, the role of other nucleotides and ions as well as the way in which their concentrations alter with metabolism requires further elucidation. A combined electrophysiological and biochemical approach is likely to prove most successful in establishing which second messenger systems contribute to the physiological regulation of the ATP-sensitive K-channel. Finally, the close correlation between cell metabolism and the activity of the ATP-sensitive K-channel raises the intriguing possibility that disorders of cell metabolism might produce alterations in channel activity and consequent changes in cell function.


Comparison of pulmonary artery and transpulmonary thermodilution cardiac output measurements in unsedated newborn calves.
To compare the agreement, repeatability and trending ability of transpulmonary thermodilution (TPTD) and pulmonary artery thermodilution (PATD) cardiac output (Q˙t) measurements in unsedated newborn calves. Prospective experimental trial. Eight newborn calves weighing a median (range) of 53 (46-59) kg. Pulmonary and femoral artery thermodilution catheters were placed under local anaesthesia. A total of 382 PATD and TPTD Q˙t measurements were performed simultaneously. Cardiac output was influenced by intravenous doxapram and theophylline in a randomized crossover fashion. Bland-Altman analysis for multiple comparisons, concordance and polar plots were used to assess TPTD against PATD. Median (range) cardiac index values measured with PATD and TPTD were 197 mL kg(-1) minute(-1) (74-335 mL kg(-1) minute(-1)) and 196 mL kg(-1) minute(-1) (59-395 mL kg(-1) minute(-1)), respec-tively. A small mean bias of -3 mL kg(-1) minute(-1) with limits of agreement (LOA) of -64 to 58 mL kg(-1) minute(-1) and a percentage error of 31% were found. Eighty-two mean values were calculated. This reduced the LOA to -50 to 41 mL kg(-1) minute(-1) with a similar small bias and a percentage error of 23%. Mean TPTD tracked changes in Q˙t compared with mean PATD with 90% concordance, a mean polar angle of 6° and radial LOA of 43°, indicating marginal trending ability. Keeping the femoral artery catheter patent and obtaining acceptable measurements were very challenging because the calves were not used to being restrained. Calf movement had less influence on PATD. We recommend that PATD remains the reference method to measure Q˙t in unsedated newborn calves. However, the robust results of the evaluation of the less invasive TPTD technique warrants further evaluation taking into account the difficulties reported in this study.


Dynamic light scattering microscopy. A novel optical technique to image submicroscopic motions. II: Experimental applications.
An experimental verification of an optical microscope technique to create spatial map images of dynamically scattered light fluctuation decay rates is presented. The dynamic light scattering microscopy technique is demonstrated on polystyrene beads and living macrophage cells. With a slow progressive scan charge-coupled device camera employed in a streak-like mode, rapid intensity fluctuations with timescales the order of milliseconds can be recorded from these samples. From such streak images, the autocorrelation function of these fluctuations can be computed at each location in the sample. The characteristic decay times of the autocorrelation functions report the rates of motion of scattering centers. These rates show reasonable agreement to theoretically expected values for known samples with good signal/noise ratio. The rates can be used to construct an image-like spatial map of the rapidity of submicroscopic motions of scattering centers.


Nanoimprinted diffraction gratings for crystalline silicon solar cells: implementation, characterization and simulation.
Light trapping is becoming of increasing importance in crystalline silicon solar cells as thinner wafers are used to reduce costs. In this work, we report on light trapping by rear-side diffraction gratings produced by nano-imprint lithography using interference lithography as the mastering technology. Gratings fabricated on crystalline silicon wafers are shown to provide significant absorption enhancements. Through a combination of optical measurement and simulation, it is shown that the crossed grating provides better absorption enhancement than the linear grating, and that the parasitic reflector absorption is reduced by planarizing the rear reflector, leading to an increase in the useful absorption in the silicon. Finally, electro-optical simulations are performed of solar cells employing the fabricated grating structures to estimate efficiency enhancement potential.


Terahertz spectroscopy studies on epitaxial vanadium dioxide thin films across the metal-insulator transition.
We present results on terahertz (THz) spectroscopy on epitaxial vanadium dioxide (VO(2)) films grown on sapphire across the metal-insulator transition. X-ray diffraction indicates the VO(2) film is highly oriented with the crystallographic relationship: (002)(film)//(0006)(sub) and [010](film)//[2 ̅1 ̅10](sub). THz studies measuring the change in transmission as a function of temperature demonstrate an 85% reduction in transmission as the thin film completes its phase transition to the conducting phase, which is much greater than the previous observation on polycrystalline films. This indicates the crucial role of microstructure and phase homogeneity in influencing THz properties.