Exploring the Career Motivations, Strengths, and Challenges of Autistic and Non-autistic University Students: Insights From a Participatory Study.
Supports for the growing number of autistic university students often focus on helping them succeed in university. However, even educated autistic people experience discrimination and other challenges which can make it very difficult for them to obtain meaningful jobs. Little remains known about how universities can better support their autistic students and alumni in overcoming barriers to meaningful employment. In this participatory study, a team of autistic and non-autistic researchers asked autistic (n = 92) and non-autistic (n = 774) university students about their career aspirations, strengths they believe will help them succeed in their "dream jobs," and obstacles they expect to encounter. Autistic participants' top goal in attending college was to improve their career prospects. However, relatively few autistic students reported learning career-specific skills at university. Autistic students were more likely to seek an academic job and less likely to seek a career in healthcare than non-autistic students. Autistic students highlighted writing skills and detail orientation as strengths that could help them succeed in their dream jobs more often than non-autistic students. However, they were also more likely to expect discrimination, social, and psychological difficulties to stand in the way of their dream jobs. These findings suggest that universities should prioritize experiential learning opportunities to help autistic (and non-autistic) students develop employment-related skills while providing mental health supports. Universities should demonstrate their commitment to supporting diverse learners by seeking out and hiring autistic professionals and by teaching their own staff and employers how to appreciate and support autistic colleagues.


Planning of ballistic movement following stroke: insights from the startle reflex.
Following stroke, reaching movements are slow, segmented, and variable. It is unclear if these deficits result from a poorly constructed movement plan or an inability to voluntarily execute an appropriate plan. The acoustic startle reflex provides a means to initiate a motor plan involuntarily. In the presence of a movement plan, startling acoustic stimulus triggers non-voluntary early execution of planned movement, a phenomenon known as the startReact response. In unimpaired individuals, the startReact response is identical to a voluntarily initiated movement, except that it is elicited 30-40 ms. As the startReact response is thought to be mediated by brainstem pathways, we hypothesized that the startReact response is intact in stroke subjects. If startReact is intact, it may be possible to elicit more task-appropriate patterns of muscle activation than can be elicited voluntarily. We found that startReact responses were intact following stroke. Responses were initiated as rapidly as those in unimpaired subjects, and with muscle coordination patterns resembling those seen during unimpaired volitional movements. Results were striking for elbow flexion movements, which demonstrated no significant differences between the startReact responses elicited in our stroke and unimpaired subject groups. The results during planned extension movements were less straightforward for stroke subjects, since the startReact response exhibited task inappropriate activity in the flexors. This inappropriate activity diminished over time. This adaptation suggests that the inappropriate activity was transient in nature and not related to the underlying movement plan. We hypothesize that the task-inappropriate flexor activity during extension results from an inability to suppress the classic startle reflex, which primarily influences flexor muscles and adapts rapidly with successive stimuli. These results indicate that stroke subjects are capable of planning ballistic elbow movements, and that when these planned movements are involuntarily executed they can be as rapid and appropriate as those in unimpaired individuals.


Evidence-based chronic heart failure management programs: reality or myth?
Chronic heart failure management programmes (CHF-MPs) have become part of standard care for patients with chronic heart failure (CHF). To investigate whether programmes had applied evidence-based expert clinical guidelines to optimise patient outcomes. Prospective cross-sectional survey was used to conduct a national audit. Community setting of CHF-MPs for patients after discharge. All CHF-MPs operating during 2005-2006 (n = 55). 10-50 consecutive patients from 48 programmes were also recruited (n = 1157). (1) Characteristics and interventions used within each CHF-MP and (2) characteristics of patients enrolled into these programmes. Overall, there was a disproportionate distribution of CHF-MPs across Australia. Only 6.3% of hospitals nationally provided a CHF-MP. A total of 8000 post-discharge CHF patients (median, 126; IQR, 26-260) were managed via CHF-MPs representing only 20% of the potential national case load. Significantly, 16% of the case load comprised patients in functional New York Heart Association class I with no evidence of these patients having had previous echocardiography to confirm a diagnosis of CHF. Heterogeneity of CHF-MPs in applied models of care was evident with 70% of CHF-MPs offering a hybrid model (a combination of heart failure outpatient clinics and home visits), 20% conducting home visits and 16% an extended rehabilitation model of care. Less than half (44%) allowed heart failure nurses to titrate medications. The main medications that were titrated in these programmes were diuretics (n = 23, 96%), beta-blockers (n = 17, 71%), ACE inhibitors (n = 14, 58%) and spironolactone (n = 9, 38%). CHF-MPs are being implemented rapidly throughout Australia. However, many of these programmes do not adhere to expert clinical guidelines for the management of patients with CHF. This poor translation of evidence into practice highlights the inconsistency and questions the quality of health-related outcomes for these patients.


Emergence of a global science-business initiative for ocean stewardship.
The ocean represents a fundamental source of micronutrients and protein for a growing world population. Seafood is a highly traded and sought after commodity on international markets, and is critically dependent on healthy marine ecosystems. A global trend of wild stocks being overfished and in decline, as well as multiple sustainability challenges associated with a rapid growth of aquaculture, represent key concerns in relation to the United Nations Sustainable Development Goals. Existing efforts aimed to improve the sustainability of seafood production have generated important progress, primarily at the local and national levels, but have yet to effectively address the global challenges associated with the ocean. This study highlights the importance of transnational corporations in enabling transformative change, and thereby contributes to advancing the limited understanding of large-scale private actors within the sustainability science literature. We describe how we engaged with large seafood producers to coproduce a global science-business initiative for ocean stewardship. We suggest that this initiative is improving the prospects for transformative change by providing novel links between science and business, between wild-capture fisheries and aquaculture, and across geographical space. We argue that scientists can play an important role in facilitating change by connecting knowledge to action among global actors, while recognizing risks associated with such engagement. The methods developed through this case study contribute to identifying key competences in sustainability science and hold promises for other sectors as well.


Computational investigation of metal organic frameworks for storage and delivery of anticancer drugs.
Metal organic frameworks (MOFs) have been recently used in biomedical applications such as drug storage and drug delivery due to their large surface areas, high pore volumes, and tunable physical and chemical characteristics. In this study, we investigated MOF-74 materials for efficient storage and delivery of two anticancer drug molecules, methotrexate (MTX) and 5-fluorouracil (5-FU). We initially compared the results of our molecular simulations with the available experimental data for the MTX and 5-FU uptakes of various MOFs. Motivated by the good agreement between experiments and simulations, we computed MTX and 5-FU uptakes in 10 different MOF-74 materials having various physical and chemical properties. At low fugacity, MTX adsorption is favored over 5-FU since MTX has stronger interactions with the MOFs whereas at high fugacity, 5-FU adsorption is favored over MTX due to the entropic effects. Our results showed that MOF-74 materials outperform the MTX and 5-FU storage capacities of traditional materials such as polymeric nanoparticles and two dimensional layered nanomaterials. We also examined the diffusion of drug molecules in MOFs considering both single-component and mixture transport for the first time in the literature. Both drug molecules diffuse slowly in MOFs suggesting that MOF-74 materials are strong alternatives to traditional porous materials for delivery of MTX and 5-FU. This computational study will be useful to effectively identify the most promising MOFs for target drug delivery applications prior to experiments. Our results will also guide the experiments for the design and development of MOFs as anticancer drug carrier systems.


FANCJ is a structure-specific DNA helicase associated with the maintenance of genomic G/C tracts.
Fanconi anemia (FA) is a heritable human cancer-susceptibility disorder, delineating a genetically heterogenous pathway for the repair of replication-blocking lesions such as interstrand DNA cross-links. Here we demonstrate that one component of this pathway, FANCJ, is a structure-specific DNA helicase that dissociates guanine quadruplex DNA (G4 DNA) in vitro. Moreover, in contrast with previously identified G4 DNA helicases, such as the Bloom's helicase (BLM), FANCJ unwinds G4 substrates with 5'-3' polarity. In the FA-J human patient cell line EUFA0030 the loss of FANCJ G4 unwinding function correlates with the accumulation of large genomic deletions in the vicinity of sequences, which match the G4 DNA signature. Together these findings support a role for FANCJ in the maintenance of potentially unstable genomic G/C tracts during replication.


Parasitism of epidermal Langerhans cells in experimental cutaneous leishmaniasis with Leishmania major.
Murine epidermal Langerhans cells (LC) have been demonstrated to stimulate a vigorous T cell response to Leishmania major, a cause of human cutaneous leishmaniasis. It was therefore of interest to analyze whether LC can take up viable parasites. Epidermal cells were obtained from mouse ear skin for incubation with L. major and subsequent detection of intracellular parasites by cytochemistry. Freshly isolated LC, but not cultured LC, phagocytosed L. major and the uptake was inhibited by antibodies to the complement receptor type 3. Electron microscopic studies revealed the presence of viable amastigotes within LC. Moreover, with double-labeling techniques, L. major-containing LC could also be detected in infected skin. The results demonstrate that LC can internalize L. major. Since the number of organisms per infected LC remained consistently low, the prime task of LC may not be the promotion of parasite spreading but the presentation of L. major antigen to T cells and, thus, the regulation of the cellular immunity during cutaneous leishmaniasis.


Neuronal acetylcholine receptors: fate of surface and internal pools in cell culture.
Chick ciliary ganglion neurons have nicotinic ACh receptors that mediate synaptic input to the cells. Ultrastructural studies with a monoclonal antibody that recognizes the neuronal ACh receptor have previously shown that, in addition to a predominantly synaptic location for the receptors on the neuron surface in vivo, substantial amounts of intracellular receptor are present as well. Here we report that intracellular receptor and smaller receptor-related components make up at least two-thirds of the total antibody binding sites associated with the ciliary ganglion neurons in cell culture. The intracellular sites for the most part represent integral membrane components that bind to concanavalin A when solubilized, indicating that the components are glycosylated. Sucrose gradient analysis shows that the intracellular material includes a 10 S component, likely to represent assembled receptor, along with species sedimenting in the 5-9 S range. Blocking the surface sites with unlabeled antibody and measuring the appearance of the new receptor on the cell surface with radiolabeled antibody indicates that the receptors are inserted into the plasma membrane at a rate equivalent to about 4% of the total surface receptor per hour. The transit time for newly synthesized receptor to reach the cell surface appears to be 2-3 hr. These observations suggest that about 5% of the intracellular receptors are transported to the cell surface in culture. The half-life of ACh receptors in the plasma membrane was estimated by 2 different approaches to be about 22 hr. Surface and internal sites respond in a qualitatively similar way to external agents that specifically modulate cholinergic receptors.(ABSTRACT TRUNCATED AT 250 WORDS)


Variation in implementation and use of computerized clinical reminders in an integrated healthcare system.
To identify patterns of use of computerized clinical reminders (CCRs) across an integrated healthcare system and describe institutional factors associated with their implementation. Cross-sectional study. At a national electronic health record (EHR) meeting, we surveyed 261 participants from 104 Veterans Health Administration (VHA) healthcare facilities regarding the number and types of CCRs available at each facility. Potential explanatory measures included perceived utility and ease of use of CCRs, training and personnel support for computer use, EHR functionalities, and performance data feedback to providers at each facility. The number of conditions with CCRs in use at a facility ranged from 1 to 15; most reported implementation of reminders for 10 of the 15 conditions surveyed. The most commonly implemented CCRs, used in more than 85% of facilities, were for conditions with VHA national performance measures (eg, tobacco cessation, immunizations, diabetes mellitus). The least commonly implemented CCRs were for post-deployment health evaluation and management, medically unexplained symptoms, and erectile dysfunction. Facilities that had implemented greater numbers of clinical reminders had providers who reported greater ease of use and utility of the reminders (P= .01). VHA facilities vary markedly in their implementation of CCRs. This effect may be partly explained by greater incorporation of clinical reminders for conditions with performance measures. Further study is needed to determine how to best implement clinical reminders and the institutional factors important in their use.


Acetaminophen combinations protect against iron-induced cardiac damage in gerbils.
This study tested if acetaminophen, N-methyl-D-glucamine dithiocarbamate (NMGDTC), deferoxamine, and combinations of these agents reduce excess iron content, prevent iron-induced pathology, reduce cardiac arrhythmias, and reduce mortality in iron-overloaded gerbils. Eight groups of 16 gerbils received iron dextran injections (ferric hydroxide dextran complex, 120 mg/kg, ip) or saline solution (controls) twice/wk for 8 wk. The 8 groups were treated every Monday, Wednesday, and Friday with one of the following: saline control, acetaminophen, 150 mg/kg, ip), acetaminophen (150 mg/kg, po), deferoxamine, 83 mg/kg, ip), NMGDTC (200 mg/kg, ip), or combinations of acetaminophen (75 mg/kg) with deferoxamine (42 mg/kg, each ip, separately) or acetaminophen (75 mg/kg) with NMGDTC (100 mg/kg, each ip, separately). The treatments were given 4 hr after each iron injection on days when both iron administration and treatment occurred during iron overloading (8 wk) and were continued 4 wk thereafter. Echocardiography (ECHO) was used to evaluate iron-induced cardiac changes and detect arrhythmias. Acetaminophen and NMGDTC, or combinations thereof, reduced cardiac and hepatic excess iron content as measured by inductively coupled plasma atomic emission spectrometry (ICP-AES). Acetaminophen was effective whether administered po or ip. Acetaminophen treatment had a positive inotropic effect on cardiac function. Acetaminophen-deferoxamine combination conferred equal cardioprotection as acetaminophen or deferoxamine alone, was equally able to remove hepatic iron, and was superior to either acetaminophen or deferoxamine in removing cardiac iron from iron-overloaded gerbils. Acetaminophen-NMGDTC combination was also effective in removing cardiac and hepatic iron and protecting against iron-induced cardiac damage. ECHO evaluation of iron-overloaded, untreated gerbils demonstrated a high incidence of cardiac arrhythmias, usually PVCs (10/16 = 63%), and mortality prior to completion of the experiment (4/16 = 25%). All treatments except deferoxamine, alone, reduced the incidence of cardiac arrhythmias and deaths. All treatments reduced iron-induced increases in hepatic and cardiac weights. This study demonstrates injection alternates that are equally or more effective than deferoxamine injections and shows oral acetaminophen to be effective in treatment of iron-overload and associated cardiac complications.


Retrieval of wave aberration from point spread function or optical transfer function data.
This paper describes the digital retrieval method of the wave aberration of an optical system from the point spread function or the optical transfer function data of the system. The Gerchberg-Saxton algorithm is used as the iterative retrieval technique of the wave aberration with additional information about the type of aberration. The usefulness of the proposed method is confirmed by computer simulations. Several problems associated with the retrieval procedure are indicated by elementary experiments with a computer generated hologram as well as by computer simulations.


The effect of long-term intraocular pressure reduction on the differential light sensitivity in glaucoma suspects.
This study was undertaken to observe the effect on the differential light sensitivity in glaucoma suspects produced by a long-term reduction in intraocular pressure (IOP) with timolol maleate. The results are taken from an ongoing 6 year follow-up study of glaucoma suspects randomly selected for treatment and nontreatment. We present fine-grid meridional data, recorded every 4 months by automated perimetry, of all 46 patients (24 treated and 22 untreated) who completed the 6 year follow-up without developing localized visual field defects, acquired optic disc changes and whose IOP was not judged clinically dangerous during the follow-up. Methods of analyzing the profile sensitivity, the profile slope and the sensitivity of specific locations over the follow-up are described. The results show that the long-term fluctuation in differential light sensitivity in the two groups was not significantly different (P = 0.395) and that the sensitivity at most of the locations remained stable. The number of stable locations was not significantly different in the two groups (P = 0.412) and there was also no difference in the number of locations where the sensitivity appeared to decrease (P = 0.193) or increase (P = 0.540). Analysis of covariance showed no group difference in the profile sensitivity or the profile slope and that these variables remained stable in both groups over the 6 year period. Although the treated group maintained a consistently lower IOP than the untreated controls, our results showed that long-term pressure reduction with timolol in glaucoma suspects appeared not to influence the differential light sensitivity in the tested meridian.


Elevated levels of circulating microRNA-200 family members correlate with serous epithelial ovarian cancer.
There is a critical need for improved diagnostic markers for high grade serous epithelial ovarian cancer (SEOC). MicroRNAs are stable in the circulation and may have utility as biomarkers of malignancy. We investigated whether levels of serum microRNA could discriminate women with high-grade SEOC from age matched healthy volunteers. To identify microRNA of interest, microRNA expression profiling was performed on 4 SEOC cell lines and normal human ovarian surface epithelial cells. Total RNA was extracted from 500 μL aliquots of serum collected from patients with SEOC (n = 28) and age-matched healthy donors (n = 28). Serum microRNA levels were assessed by quantitative RT-PCR following preamplification. microRNA (miR)-182, miR-200a, miR-200b and miR-200c were highly overexpressed in the SEOC cell lines relative to normal human ovarian surface epithelial cells and were assessed in RNA extracted from serum as candidate biomarkers. miR-103, miR-92a and miR -638 had relatively invariant expression across all ovarian cell lines, and with small-nucleolar C/D box 48 (RNU48) were assessed in RNA extracted from serum as candidate endogenous normalizers. No correlation between serum levels and age were observed (age range 30-79 years) for any of these microRNA or RNU48. Individually, miR-200a, miR-200b and miR-200c normalized to serum volume and miR-103 were significantly higher in serum of the SEOC cohort (P < 0.05; 0.05; 0.0005 respectively) and in combination, miR-200b + miR-200c normalized to serum volume and miR-103 was the best predictive classifier of SEOC (ROC-AUC = 0.784). This predictive model (miR-200b + miR-200c) was further confirmed by leave one out cross validation (AUC = 0.784). We identified serum microRNAs able to discriminate patients with high grade SEOC from age-matched healthy controls. The addition of these microRNAs to current testing regimes may improve diagnosis for women with SEOC.


Uniform Partitioning of Data Grid for Association Detection.
Inferring appropriate information from large datasets has become important. In particular, identifying relationships among variables in these datasets has far-reaching impacts. In this article, we introduce the uniform information coefficient (UIC), which measures the amount of dependence between two multidimensional variables and is able to detect both linear and non-linear associations. Our proposed UIC is inspired by the maximal information coefficient (MIC) [1].; however, the MIC was originally designed to measure dependence between two one-dimensional variables. Unlike the MIC calculation that depends on the type of association between two variables, we show that the UIC calculation is less computationally expensive and more robust to the type of association between two variables. The UIC achieves this by replacing the dynamic programming step in the MIC calculation with a simpler technique based on the uniform partitioning of the data grid. This computational efficiency comes at the cost of not maximizing the information coefficient as done by the MIC algorithm. We present theoretical guarantees for the performance of the UIC and a variety of experiments to demonstrate its quality in detecting associations.


Experimental and theoretical analysis for improved microscope design of optical projection tomographic microscopy.
We present theoretical and experimental results of axial displacement of objects relative to a fixed condenser focal plane (FP) in optical projection tomographic microscopy (OPTM). OPTM produces three-dimensional, reconstructed images of single cells from two-dimensional projections. The cell rotates in a microcapillary to acquire projections from different perspectives where the objective FP is scanned through the cell while the condenser FP remains fixed at the center of the microcapillary. This work uses a combination of experimental and theoretical methods to improve the OPTM instrument design.


Toward the sustainability of health interventions implemented in sub-Saharan Africa: a systematic review and conceptual framework.
Sub-Saharan Africa (SSA) is facing a double burden of disease with a rising prevalence of non-communicable diseases (NCDs) while the burden of communicable diseases (CDs) remains high. Despite these challenges, there remains a significant need to understand how or under what conditions health interventions implemented in sub-Saharan Africa are sustained. The purpose of this study was to conduct a systematic review of empirical literature to explore how health interventions implemented in SSA are sustained. We searched MEDLINE, Biological Abstracts, CINAHL, Embase, PsycInfo, SCIELO, Web of Science, and Google Scholar for available research investigating the sustainability of health interventions implemented in sub-Saharan Africa. We also used narrative synthesis to examine factors whether positive or negative that may influence the sustainability of health interventions in the region. The search identified 1819 citations, and following removal of duplicates and our inclusion/exclusion criteria, only 41 papers were eligible for inclusion in the review. Twenty-six countries were represented in this review, with Kenya and Nigeria having the most representation of available studies examining sustainability. Study dates ranged from 1996 to 2015. Of note, majority of these studies (30 %) were published in 2014. The most common framework utilized was the sustainability framework, which was discussed in four of the studies. Nineteen out of 41 studies (46 %) reported sustainability outcomes focused on communicable diseases, with HIV and AIDS represented in majority of the studies, followed by malaria. Only 21 out of 41 studies had clear definitions of sustainability. Community ownership and mobilization were recognized by many of the reviewed studies as crucial facilitators for intervention sustainability, both early on and after intervention implementation, while social and ecological conditions as well as societal upheavals were barriers that influenced the sustainment of interventions in sub-Saharan Africa. The sustainability of health interventions implemented in sub-Saharan Africa is inevitable given the double burden of diseases, health care worker shortage, weak health systems, and limited resources. We propose a conceptual framework that draws attention to sustainability as a core component of the overall life cycle of interventions implemented in the region.


Effect of online hemodiafiltration on all-cause mortality and cardiovascular outcomes.
In patients with ESRD, the effects of online hemodiafiltration on all-cause mortality and cardiovascular events are unclear. In this prospective study, we randomly assigned 714 chronic hemodialysis patients to online postdilution hemodiafiltration (n=358) or to continue low-flux hemodialysis (n=356). The primary outcome measure was all-cause mortality. The main secondary endpoint was a composite of major cardiovascular events, including death from cardiovascular causes, nonfatal myocardial infarction, nonfatal stroke, therapeutic coronary intervention, therapeutic carotid intervention, vascular intervention, or amputation. After a mean 3.0 years of follow-up (range, 0.4-6.6 years), we did not detect a significant difference between treatment groups with regard to all-cause mortality (121 versus 127 deaths per 1000 person-years in the online hemodiafiltration and low-flux hemodialysis groups, respectively; hazard ratio, 0.95; 95% confidence interval, 0.75-1.20). The incidences of cardiovascular events were 127 and 116 per 1000 person-years, respectively (hazard ratio, 1.07; 95% confidence interval, 0.83-1.39). Receiving high-volume hemodiafiltration during the trial associated with lower all-cause mortality, a finding that persisted after adjusting for potential confounders and dialysis facility. In conclusion, this trial did not detect a beneficial effect of hemodiafiltration on all-cause mortality and cardiovascular events compared with low-flux hemodialysis. On-treatment analysis suggests the possibility of a survival benefit among patients who receive high-volume hemodiafiltration, although this subgroup finding requires confirmation.


Deep brain stimulation of the nucleus basalis of Meynert in Alzheimer's dementia.
Cholinergic neurons of the medial forebrain are considered important contributors to brain plasticity and neuromodulation. A reduction of cholinergic innervation can lead to pathophysiological changes of neurotransmission and is observed in Alzheimer's disease. Here we report on six patients with mild to moderate Alzheimer's disease (AD) treated with bilateral low-frequency deep brain stimulation (DBS) of the nucleus basalis of Meynert (NBM). During a four-week double-blind sham-controlled phase and a subsequent 11-month follow-up open label period, clinical outcome was assessed by neuropsychological examination using the Alzheimer's Disease Assessment Scale-cognitive subscale as the primary outcome measure. Electroencephalography and [(18)F]-fluoro-desoxyglucose positron emission tomography were, besides others, secondary endpoints. On the basis of stable or improved primary outcome parameters twelve months after surgery, four of the six patients were considered responders. No severe or non-transitional side effects related to the stimulation were observed. Taking into account all limitations of a pilot study, we conclude that DBS of the NBM is both technically feasible and well tolerated.


The AfaR small RNA controls expression of the AfaD-VIII invasin in pathogenic Escherichia coli strains.
Pathogenic Escherichia coli strains carrying the afa-8 gene cluster are frequently associated with extra-intestinal infections in humans and animals. The afa-8 A to E genes determine the formation of an afimbrial adhesive sheath consisting of the AfaD-VIII invasin and the AfaE-VIII adhesin at the bacterial cell surface. This structure is thought to be required for host colonization. We characterized a new gene encoding the small RNA AfaR, which is transcribed in cis from the complementary strand of the 3' untranslated region of the afaD messenger RNA, within the afaD-afaE intercistronic region. AfaR is a trans-acting Hfq-dependent antisense small RNA that binds the 5' untranslated region of the afaD messenger RNA, initiating several ribonuclease E-dependent cleavages, thereby downregulating production of the AfaD-VIII invasin. AfaR transcription is dependent on σ(E), a member of the stress response family of extracytoplasmic alternative sigma factors. We found that the AfaR-dependent regulatory pathway was controlled by temperature, allowing the production of the AfaD-VIII invasin at temperatures above 37 °C. Our findings suggest that the entry of afa-8-positive pathogenic E. coli strains into epithelial cells is tightly regulated by the AfaR small RNA.


Frames of reference for mapping tactile stimuli in brain-damaged patients.
Twelve normal controls, twelve left-brain-damaged patients, and thirty-six right-brain-damaged patients with or without tactile extinction or tactile neglect were asked to report light touches delivered to the left or the right hand or simultaneously to both hands. The hands could be in anatomic position or one hand could cross over the other. Moreover, the two hands could be in the left or the right hemispace or across the corporeal midline. Controls and nontactile-extinction groups performed better when the hands were in anatomical than in crossed position. By contrast, patients with tactile extinction detected contralesional stimuli with higher accuracy in crossed than in anatomical position. This result suggests that, in these patients, impairments in detecting contralesional stimuli can be due not only to sensory but also to spatial factors contingent upon the position of the hands. There was no interaction between the effect of crossing the hands and the hemispace where the crossing took place. This suggests that coding the position of a hand as left or right does not necessarily occur in relation to the bodily midline, but it may arise from the computation of the position of the other hand.


[Intestinal pneumatosis in pediatrics. Report of 72 cases].
We analyzed 72 cases of pneumatosis intestinalis at the Hospital Infantil de México during a 32 years period. We found the higehst incidence in children under 6 months of age. In the new-born period, the entity is associated with necrotizing entrocolitis and in the older children group, this alteration is associated with gastroenteritis. The diagnosis was made by radiology in 93% of the cases and in 7%, it was made at the surgical event. We propose 3 mechanisms in the pathophysiology of the entity having all of them disruption of the integrity of the intestinal mucosa and higher pressure of the intraluminal gas. The mortality rate was high because we included cases from the initiation of the hospital's activities (1943). The conclusion is: 1) The prognosis is based on an early diagnosis. 2) It is imperative to take proper care of the complication. 3) It is also very important to give a rest for variable period of time to the injured intestine with parenteral feeding and eventually, elemental feeding.


The effects of acid etching on the pulpodentin complex.
Acid etching of dentin is used by many bonding systems to remove the smear layer and permit bonding directly to the dentin matrix. Although early animal studies indicated that acid etching caused moderate to severe pulpal reactions, there is a high probability that the pulpal irritation may have been due to microleakage of bacteria and their products. As these reactions are not seen following acid etching of dentin using newer dentin bonding systems, it is clear that one can acid etch dentin if, and only if, one can seal the dentin with subsequently placed bonding systems. Because acid etching increases dentin permeability and dentin wetness, successful bonding of adhesive resins to acid-etched dentin requires the use of hydrophilic resins that bond equally well to both peritubular and intratubular dentin. Future trends seem to be toward lowering both the concentration of acids and the time of etching of dentin. While all bonding systems should be carefully scrutinized prior to marketing, the future looks very promising for the use of adhesive resins on acid-etched dentin.


Safety and efficacy of percutaneous intramyocardial bone marrow cell injection for chronic myocardial ischemia: Long-term results.
Intramyocardial injection of bone marrow cells (BMC) in refractory angina patients with chronic myocardial ischemia has shown to be safe and improve clinical status during short-term follow-up. However, scarce data are available on long-term (>12 months) safety and efficacy. Therefore, the occurrence of clinical events and the long-term clinical effects of intramyocardial BMC injection were evaluated in patients with chronic myocardial ischemia up to 10 years after treatment. Patients (n = 100, age 64 ± 9 years, male 88%) with chronic myocardial ischemia who underwent intramyocardial BMC injection between 2004 and 2010 were evaluated. During yearly outpatient clinic visits, the occurrence of clinical events was documented. In addition, clinical status was assessed according to the Canadian Cardiovascular Society (CCS) score and quality of life was measured using the Seattle Angina Questionnaire. These parameters were evaluated at baseline and during the first year, followed by cross-sectional long-term follow-up which was performed in 2011 and 2014. No adverse events considered related to the procedure occurred during 10 years of follow-up. Observed annual mortality rate and annual myocardial infarction rate were 3.8% and 1.9% per year, respectively. When compared to baseline, CCS class and quality of life remained significantly better during 5-year follow-up after BMC treatment (both P < 0.05). The present long-term follow-up study shows that intramyocardial BMC injection in patients with chronic myocardial ischemia is safe and improves both angina complaints and quality of life up to 5 years after BMC treatment.


Prosthetic Manhood in the Soviet Union at the End of World War II.
Millions of Soviet soldiers were disabled as a direct consequence of their service in the Second World War. Yet despite its expressions of gratitude for their sacrifices, the state evinced a great deal of discomfort regarding their damaged bodies. The countless armless and legless veterans were a constant reminder of the destruction suffered by the country as a whole, an association increasingly incompatible with the postwar agenda of wholesale reconstruction. This article focuses on a key strategy for erasing the scars of war, one with ostensibly unambiguous benefit for the disabled themselves: the development of prostheses. In addition to fostering independence from others and ultimately from the state, artificial limbs would facilitate the veterans' return to the kinds of socially useful labor by which the country defined itself. In so doing, this strategy engendered the establishment of a new model of masculinity: a prosthetic manhood.


Mechanisms of recovery from aphasia: evidence from serial xenon 133 cerebral blood flow studies.
In 21 patients who suffered aphasia resulting from left hemisphere ischemic infarction, the xenon 133 inhalation cerebral blood flow technique was used to measure cerebral blood flow within 3 months and 5 to 12 months after stroke. In addition to baseline measurements, cerebral blood flow measurements were also carried out while the patients were performing purposeful listening. In patients with incomplete recovery of comprehension and left posterior temporal-inferior parietal lesions, greater cerebral blood flow occurred with listening in the right inferior frontal region in the late studies than in the early studies. In patients with nearly complete recovery of comprehension and without left posterior temporal-inferior parietal lesions, early listening studies showed diffuse right hemisphere increases in cerebral blood flow. Later listening studies in this latter patient group showed greater cerebral blood flow in the left posterior temporal-inferior parietal region. The study provides evidence for participation of the right hemisphere in language comprehension in recovering aphasics, and for later return of function in left hemisphere regions that may have been functionally impaired early during recovery.


Asymmetric hydration structure around calcium ion restricted in micropores fabricated in activated carbons.
The adsorbed phase and hydration structure of an aqueous solution of Ca(NO3)2 restricted in micropores fabricated in activated carbons (ACs) having different average pore widths (0.63 and 1.1 nm) were investigated with the analysis of adsorption isotherms and x-ray absorption fine structure (XAFS) spectra on Ca K-edge. The adsorbed density of Ca(2+) per unit micropore volume in the narrower pore was higher than in the wider pore, while the adsorbed amount per unit mass of carbon with the narrower pore was half of the amount of ACs with the larger pore. On the other hand, variations in the bands assigned to double-electron (KM I) and 1s → 3d excitations in XAFS spectra demonstrate the formation of a distorted hydration cluster around Ca(2+) in the micropore, although the structural parameters of hydrated Ca(2+) in the micropores were almost consistent with the bulk aqueous solution, as revealed by the analysis of extended XAFS (EXAFS) spectra. In contrast to the hydration structure of monovalent ions such as Rb(+), which generally presents a dehydrated structure in smaller than 1 nm micropores in ACs, the present study clearly explains that the non-spherically-symmetric structure of hydrated Ca(2+) restricted in carbon micropores whose sizes are around 1 nm is experimentally revealed where any dehydration phenomena from the first hydration shell around Ca(2+) could not be observed.


Robust Distributed Predictive Control of Waterborne AGVs-A Cooperative and Cost-Effective Approach.
Waterborne autonomous guided vessels (waterborne AGVs) moving over open waters experience environmental uncertainties. This paper proposes a novel cost-effective robust distributed control approach for waterborne AGVs. The overall system is uncertain and has independent subsystem dynamics but coupling objectives and state constraints. Waterborne AGVs determine their actions in a parallel way, while still minimizing an overall cost function and respecting coupling constraints robustly by communicating within a neighborhood. Our first contribution is the proposal of the system robustness level for the cost-effective robust distributed model predictive control (RDMPC) for waterborne AGVs. Cost-effective RDMPC models the price of robustness by explicitly considering uncertainty and system characteristics in a tube-based robust control framework. The second contribution is an efficient integrated branch & bound (B&B) and the alternating direction method of multipliers (ADMMs) algorithm for solving the cost-effective RDMPC problem. The algorithm exploits special ordered variable sets and combining branching criteria with intermediate ADMM results conducting smart search in B&B. Simulation results demonstrate the effectiveness of the proposed approach for cooperative distributed waterborne AGVs with cost-effective robustness.


Evaluation of chemopreventive effects of Acanthus ilicifolius against azoxymethane-induced aberrant Crypt Foci in the rat colon.
Acanthus ilicifolius, a mangrove medicinal plant, is traditionally used to treat a variety of diseases. The aim of this research is to assess the chemoprotective outcomes of A. ilicifolius ethanolic extract against azoxymethane (AOM) induced colonic aberrant crypt foci (ACF) in rats. In our study, rats were arranged in to five groups. Rats in the normal control group were given subcutaneous injections of normal saline once weekly for 2 weeks. The AOM control, reference and treatment groups were given subcutaneous injection of AOM, 15 mg/kg body weight, once weekly for 2 weeks each. The reference group was treated with 35 mg/kg 5-Fluorouracil via intraperitoneal injection once weekly for 8 weeks, and the treatment groups were administered by gavage with 250 and 500 mg/kg A. ilicifolius extract daily for 8 weeks. Both normal and AOM control groups received the vehicle; 10% Tween-20 only. Rats treated with 250 mg/kg and 500 mg/kg of A. ilicifolius extracts showed a decrease in the mean number of ACF by 65% and 53%, respectively. Those fed with A. ilicifolius showed significantly decreased multiplicity of ACF formations when compared with the results from the AOM control group. The 250 mg/kg A. ilicifolius treatment group showed significant decreases in lipid peroxidation MDA levels when compared with the AOM control group. In immunohistochemistry staining, the proliferating nuclear cell antigen (PCNA)-positive cells were significantly higher in the AOM control group than in the A. ilicifolius-treated groups. RT-PCR showed that A. ilicifolius caused a change in the regulation of apoptosis-related genes expression. The results of the current study show that AOM-treated rats receiving oral exposure to A. ilicifolius demonstrated a significant decrease in the number of ACF in the colon when compared to AOM-treated rats receiving vehicle only. A ilicifolius may be an effective herbal approach for the prevention of AOM-induced ACF in the rat colon.


Hip fracture as the tracer condition.
Hip fractures represent the most severe complication of osteoporosis from the perspectives of the patient, carer, health care system and society. Given the strong association with age, numbers are set to rise significantly in the next few decades despite evidence that the age adjusted rates in some countries are either plateauing or falling. Given the almost invariable need for inpatient admission, hospital administrative data for hip fractures remain a robust measure of number of hip fractures in the community and can be extrapolated to determine the total expected number of clinical fragility fractures from the same population. Both process and outcome standards have now been developed to benchmark clinical quality in the care of patients with hip fractures and fragility fractures at other sites.


Influence of nonlinear absorption on Raman amplification in Silicon waveguides.
We model the TPA-induced free carrier absorption effect in silicon Raman amplifiers and quantify the conditions under which net gain may be obtained. The achievable Raman gain strongly depends on the free carrier lifetime, propagation loss, and on the effective Raman gain coefficient, through pump-induced broadening.


The effect of transcranial alternating current stimulation (tACS) on cognitive function in older adults with dementia.
Recent studies have shown a positive effect of transcranial alternating current stimulation (tACS), a noninvasive brain stimulation technique, on cognitive function of healthy individuals [1]. However, investigation into the effects of tACS on individuals with dementia or mild cognitive impairment (MCI) is lacking. In this pilot study, we investigated the hypothesis that following a regular schedule of challenging brain exercises combined with simultaneous tACS application would improve the working memory and cognitive function of older adults with memory impairments. Further, we explored whether pairing brain exercises with tACS would result in longer-lasting positive effects on cognitive function than brain exercises alone. A total of 17 older adults (12 males, 5 females, 70 ± 7 years), each with a diagnosis of mild to moderate dementia were enrolled in the study. All participants completed brain exercises in the lab on the following schedule: two 30-minute sessions per day, 5 days/week for 4 weeks consecutively. Eleven of the participants received brain exercises paired with tACS application at 40Hz. We evaluated cognitive function of the participants at baseline, post-intervention and 1-month followup using the Wechsler Memory Scale (WMS-IV) as an independent assessment of our brain exercises. Both the non-tACS and tACS groups significantly improved their WMS scores from baseline to post-intervention assessments. Comparison of the post-intervention and 1-month follow-up assessments indicated that the tACS group maintained their improvement significantly better than the non-tACS group.


Endogenous α-calcitonin-gene-related peptide promotes exercise-induced, physiological heart hypertrophy in mice.
It is unknown how the heart distinguishes various overloads, such as exercise or hypertension, causing either physiological or pathological hypertrophy. We hypothesize that alpha-calcitonin-gene-related peptide (αCGRP), known to be released from contracting skeletal muscles, is key at this remodelling. The hypertrophic effect of αCGRP was measured in vitro (cultured cardiac myocytes) and in vivo (magnetic resonance imaging) in mice. Exercise performance was assessed by determination of maximum oxygen consumption and time to exhaustion. Cardiac phenotype was defined by transcriptional analysis, cardiac histology and morphometry. Finally, we measured spontaneous activity, body fat content, blood volume, haemoglobin mass and skeletal muscle capillarization and fibre composition. While αCGRP exposure yielded larger cultured cardiac myocytes, exercise-induced heart hypertrophy was completely abrogated by treatment with the peptide antagonist CGRP(8-37). Exercise performance was attenuated in αCGRP(-/-) mice or CGRP(8-37) treated wild-type mice but improved in animals with higher density of cardiac CGRP receptors (CLR-tg). Spontaneous activity, body fat content, blood volume, haemoglobin mass, muscle capillarization and fibre composition were unaffected, whereas heart index and ventricular myocyte volume were reduced in αCGRP(-/-) mice and elevated in CLR-tg. Transcriptional changes seen in αCGRP(-/-) (but not CLR-tg) hearts resembled maladaptive cardiac phenotype. Alpha-calcitonin-gene-related peptide released by skeletal muscles during exercise is a hitherto unrecognized effector directing the strained heart into physiological instead of pathological adaptation. Thus, αCGRP agonists might be beneficial in heart failure patients.


Ability of a bacterial chromosome segment to invert is dictated by included material rather than flanking sequence.
Homologous recombination between sequences present in inverse order within the same chromosome can result in inversion formation. We have previously shown that inverse order sequences at some sites (permissive) recombine to generate the expected inversion; no inversions are found when the same inverse order sequences flank other (nonpermissive) regions of the chromosome. In hopes of defining how permissive and nonpermissive intervals are determined, we have constructed a strain that carries a large chromosomal inversion. Using this inversion mutant as the parent strain, we have determined the "permissivity" of a series of chromosomal sites for secondary inversions. For the set of intervals tested, permissivity seems to be dictated by the nature of the genetic material present within the chromosomal interval being tested rather than the flanking sequences or orientation of this material in the chromosome. Almost all permissive intervals include the origin or terminus of replication. We suggest that the rules for recovery of inversions reflect mechanistic restrictions on the occurrence of inversions rather than lethal consequences of the completed rearrangement.


Advances in electronic-nose technologies developed for biomedical applications.
The research and development of new electronic-nose applications in the biomedical field has accelerated at a phenomenal rate over the past 25 years. Many innovative e-nose technologies have provided solutions and applications to a wide variety of complex biomedical and healthcare problems. The purposes of this review are to present a comprehensive analysis of past and recent biomedical research findings and developments of electronic-nose sensor technologies, and to identify current and future potential e-nose applications that will continue to advance the effectiveness and efficiency of biomedical treatments and healthcare services for many years. An abundance of electronic-nose applications has been developed for a variety of healthcare sectors including diagnostics, immunology, pathology, patient recovery, pharmacology, physical therapy, physiology, preventative medicine, remote healthcare, and wound and graft healing. Specific biomedical e-nose applications range from uses in biochemical testing, blood-compatibility evaluations, disease diagnoses, and drug delivery to monitoring of metabolic levels, organ dysfunctions, and patient conditions through telemedicine. This paper summarizes the major electronic-nose technologies developed for healthcare and biomedical applications since the late 1980s when electronic aroma detection technologies were first recognized to be potentially useful in providing effective solutions to problems in the healthcare industry.


N-3 Hydroxylation of Pyrimidine-2,4-diones Yields Dual Inhibitors of HIV Reverse Transcriptase and Integrase.
A new molecular scaffold featuring an N-hydroxyimide functionality and capable of inhibiting both reverse transcriptase (RT) and integrase (IN) of Human Immunodeficiency Virus (HIV) was rationally designed based on 1-[(2-hydroxyethoxy) methyl]-6-(phenylthio)-thymine (HEPT) non-nucleoside RT inhibitors (NNRTIs). The design involves a minimal 3-N hydroxylation of the pyrimidine ring of HEPT compound to yield a chelating triad which, along with the existing benzyl group, appeared to satisfy major structural requirements for IN binding. In the mean time, this chemical modification did not severely compromise the compound's ability to inhibit RT. A preliminary structure-activity-relationship (SAR) study reveals that this N-3 OH is essential for IN inhibition and that the benzyl group on N-1 side chain is more important for IN binding than the one on C-6.


Antitumor activity of a Rhodococcus sp. Lut0910 isolated from polluted soil.
The actinomycetes strain, lut0910, was isolated from polluted soil and identified as the Rhodococcus species with 99% similarity based on the sequence analysis of 16S recombinant DNA. The extract of this strain demonstrated in vivo and in vitro antitumor activity. The treatment of two human cancer cell lines, hepatocellular carcinoma HepG2 and cervical carcinoma Hela cells, with the lut0910 extract caused the delay in cell propagation in a dose-dependent manner with an IC50 of 73.39 and 33.09 µg/mL, respectively. Also, the oral administration of lut0910 extract to the mice with a solid tumor resulted in the inhibition of tumor growth in comparison with a placebo group. The thymus and spleen indexes were significantly increased in mice groups treated with the lut0910 extract. The histopathological changes of the tumor tissues showed that there were massive necrotic areas in the tumor tissues after treatment with different doses of the lut0910 extract. Our result would provide a new way and potent source for development of new anticancer agent from the polluted environment.


Terminal symptoms in children dying suddenly and unexpectedly at home. Preliminary report of the DHSS multicentre study of postneonatal mortality.
Terminal symptoms in 145 children who died suddenly and unexpectedly at home were investigated and compared with symptoms in 154 control children. Eighty-five (59%) of the children who died had had terminal symptoms, which in 69 cases (48%) appeared to have been major. Non-specific symptoms were especially common among the children who died. Symptoms were often present for several days before death. Only 12 of the 69 children who died with major symptoms had been seen by a doctor within 24 hours before death. We conclude that many deaths in young children might be prevented if doctors and parents were more aware of the importance of non-specific symptoms as markers of life-threatening illness.


Thymoma: a clinicopathological correlation of 1470 cases.
We present 1470 surgical resections for thymoma identified in the pathology files of 14 institutions from 11 countries with the purpose of determining and correlating a simplified histological classification of thymoma and pathological staging with clinical outcome. The study population was composed of 720 men and 750 women between the ages of 12 and 86 years (average, 54.8 years). Clinically, 137 patients (17%) had a history of myasthenia gravis, 31 patients (3.8%) of other autoimmune disease, and 55 (6.8%) patients of another neoplastic process. Surgical resection was performed in all patients. Histologically, 1284 (87.13%) cases were thymomas (World Health Organization types A, B1, and B2, and mixed histologies), and 186 (12.7%) were atypical thymomas (World Health Organization type B3). Of the entire group, 630 (42.9%) were encapsulated thymomas, and 840 (57.9%) were invasive thymomas in different stages. Follow-up information was obtained in 1339 (91%) patients, who subsequently were analyzed by univariate and multivariate statistical analysis. Follow-up ranging from 1 to 384 months was obtained (mean, 69.2 months) showing tumor recurrence in 136 patients (10.1%), whereas 227 died: 64 (28.2%) due to tumor and 163 (71.8%) due to other causes. Statistical analysis shows that separation of these tumors into thymoma and atypical thymoma is statistically significant (P = .001), whereas tumor staging into categories of encapsulated, minimally invasive, and invasion into adjacent organs offers a meaningful clinical assessment with a P = .038. Our findings suggest that our simplified histological schema and pathological staging system are excellent predictors of clinical outcome.


Improving transferability of introduced species' distribution models: new tools to forecast the spread of a highly invasive seaweed.
The utility of species distribution models for applications in invasion and global change biology is critically dependent on their transferability between regions or points in time, respectively. We introduce two methods that aim to improve the transferability of presence-only models: density-based occurrence thinning and performance-based predictor selection. We evaluate the effect of these methods along with the impact of the choice of model complexity and geographic background on the transferability of a species distribution model between geographic regions. Our multifactorial experiment focuses on the notorious invasive seaweed Caulerpa cylindracea (previously Caulerpa racemosa var. cylindracea) and uses Maxent, a commonly used presence-only modeling technique. We show that model transferability is markedly improved by appropriate predictor selection, with occurrence thinning, model complexity and background choice having relatively minor effects. The data shows that, if available, occurrence records from the native and invaded regions should be combined as this leads to models with high predictive power while reducing the sensitivity to choices made in the modeling process. The inferred distribution model of Caulerpa cylindracea shows the potential for this species to further spread along the coasts of Western Europe, western Africa and the south coast of Australia.


Combined pre-operative chemotherapy with intra-arterial cisplatin and continuous intravenous adriamycin for high grade osteosarcoma.
Osteosarcoma is one of the most common juvenile malignant tumors in Korea. Combined modality treatment (pre-operative chemotherapy + limb salvage surgery + adjuvant therapy) improved the patients' overall survival and quality of life. We evaluated the efficacy and feasibility of pre-operative chemotherapy with intra-arterial (IA) cisplatin plus continuous intravenous infusion (CI) of adriamycin. We assessed the rate of limb salvage, recurrence pattern and the survival impact based on the histologic response of pre-operative chemotherapy. Fourty-one patients with histologically-proven high grade osteosarcoma of the extremities were enrolled from January 1990 to June 1995. Pre-operative chemotherapy, cisplatin 120 mg/m2 IA and adriamycin 75 mg/m2/72 h CI was administered every 3 weeks for 3 cycles, followed by limb salvage surgery if possible or by amputation. According to the histologic tumor response, if the tumor necrosis was >90%, the same regimen was administered for 3 cycles as an adjuvant therapy. A salvage regimen (Ifosfamide 7.5 gm/m2/5 d IV + high dose MTX 10 gm/m2 IV+VP-16 360 mg/m2/3 d IV) was administered every 3 weeks for 6 cycles if the tumor necrosis was <90%. Of 41 patients, 37 patients were evaluable for efficacy and toxicities, because 4 patients refused chemotherapy after 1 or 2 cycles. Twenty-one patients were male and 16 were female with median age of 16 years (range 8-41). The tumor locations were: distal femur 20, proximal tibia 8, humerus 6, distal tibia 2 and 1 in proximal femur. All but one patient, who died of neutropenic sepsis, completed the planned pre-operative therapy. Of the 36 patients who received surgery, limb salvage surgery was possible in 30 patients (83.3%) and 27 patients (75%) showed a good response (grade III 10; 27.8%, grade IV 17; 47.2%). With a median follow-up of 23 months, 3-year disease-free survival rate was 54.7% and overall survival rate was 78.3%. Of the 15 patients who recurred, the major metastatic site was the lung. No operation-related mortality was observed. Most patients experienced grade III-IV nausea, vomiting and hematologic toxicities, which were reversible with supportive cares. Pre-operative chemotherapy with IA DDP+CI ADR followed by surgery showed 75% histologic tumor response rate, 83% limb salvage rate and 54.7% 3-year disease-free survival rate with tolerable side effects. To improve the survival rate, the possible role of good salvage chemotherapy with a non-cross resistance regimen in poor responders should be evaluated.


Long-Term Stored Hemoglobin-Vesicles, a Cellular Type of Hemoglobin-Based Oxygen Carrier, Has Resuscitative Effects Comparable to That for Fresh Red Blood Cells in a Rat Model with Massive Hemorrhage without Post-Transfusion Lung Injury.
Hemoglobin-vesicles (HbV), encapsulating highly concentrated human hemoglobin in liposomes, were developed as a substitute for red blood cells (RBC) and their safety and efficacy in transfusion therapy has been confirmed in previous studies. Although HbV suspensions are structurally and physicochemically stabile for least 1-year at room temperature, based on in vitro experiments, the issue of whether the use of long-term stored HbV after a massive hemorrhage can be effective in resuscitations without adverse, post-transfusion effects remains to be clarified. We report herein on a comparison of the systemic response and the induction of organ injuries in hemorrhagic shock model rats resuscitated using 1-year-stored HbV, freshly packed RBC (PRBC-0) and by 28-day-stored packed RBC (PRBC-28). The six-hour mortality after resuscitation was not significantly different among the groups. Arterial blood pressure and blood gas parameters revealed that, using HbV, recovery from the shock state was comparable to that when PRBC-0 was used. Although no significant change was observed in serum parameters reflecting liver and kidney injuries at 6 hours after resuscitation among the three resuscitation groups, results based on Evans Blue and protein leakage in bronchoalveolar lavage fluid, the lung wet/dry weight ratio and histopathological findings indicated that HbV as well as PRBC-0 was less predisposed to result in a post-transfusion lung injury than PRBC-28, as evidenced by low levels of myeloperoxidase accumulation and subsequent oxidative damage in the lung. The findings reported herein indicate that 1-year-stored HbV can effectively function as a resuscitative fluid without the induction of post-transfused lung injury and that it is comparable to fresh PRBC, suggesting that HbV is a promising RBC substitute with a long shelf-life.


The time-course of protection of the RTS,S vaccine against malaria infections and clinical disease.
Recent publications have reported follow-up of the RTS,S/AS01 malaria vaccine candidate Phase III trials at 11 African sites for 32 months (or longer). This includes site- and time-specific estimates of incidence and efficacy against clinical disease with four different vaccination schedules. These data allow estimation of the time-course of protection against infection associated with two different ages of vaccination, both with and without a booster dose. Using an ensemble of individual-based stochastic models, each trial cohort in the Phase III trial was simulated assuming many different hypothetical profiles for the vaccine efficacy against infection in time, for both the primary course and boosting dose and including the potential for either exponential or non-exponential decay. The underlying profile of protection was determined by Bayesian fitting of these model predictions to the site- and time-specific incidence of clinical malaria over 32 months (or longer) of follow-up. Using the same stochastic models, projections of clinical efficacy in each of the sites were modelled and compared to available observed trial data. The initial protection of RTS,S immediately following three doses is estimated as providing an efficacy against infection of 65 % (when immunizing infants aged 6-12 weeks old) and 91 % (immunizing children aged 5-17 months old at first vaccination). This protection decays relatively rapidly, with an approximately exponential decay for the 6-12 weeks old cohort (with a half-life of 7.2 months); for the 5-17 months old cohort a biphasic decay with a similar half-life is predicted, with an initial rapid decay followed by a slower decay. The boosting dose was estimated to return protection to an efficacy against infection of 50-55 % for both cohorts. Estimates of clinical efficacy by trial site are consistent with those reported in the trial for all cohorts. The site- and time-specific clinical observations from the RTS,S/AS01 trial data allowed a reasonably precise estimation of the underlying vaccine protection against infection which is consistent with common underlying efficacy and decay rates across the trial sites. This calibration suggests that the decay in efficacy against clinical disease is more rapid than that against infection because of age-shifts in the incidence of disease. The dynamical models predict that clinical effectiveness will continue to decay and that likely effects beyond the time-scale of the trial will be small.


Stimulation of dopamine receptor D5 expressed on dendritic cells potentiates Th17-mediated immunity.
Dendritic cells (DCs) are responsible for priming T cells and for promoting their differentiation from naive T cells into appropriate effector cells. Emerging evidence suggests that neurotransmitters can modulate T cell-mediated immunity. However, the involvement of specific neurotransmitters or receptors remains poorly understood. In this study, we analyzed the role of dopamine in the regulation of DC function. We found that DCs express dopamine receptors as well as the machinery necessary to synthesize, store, and degrade dopamine. Notably, the expression of D5R decreased upon LPS-induced DC maturation. Deficiency of D5R on the surface of DCs impaired LPS-induced IL-23 and IL-12 production and consequently attenuated the activation and proliferation of Ag-specific CD4(+) T cells. To determine the relevance of D5R expressed on DCs in vivo, we studied the role of this receptor in the modulation of a CD4(+) T cell-driven autoimmunity model. Importantly, D5R-deficient DCs prophylactically transferred into wild-type recipients were able to reduce the severity of experimental autoimmune encephalomyelitis. Furthermore, mice transferred with D5R-deficient DCs displayed a significant reduction in the percentage of Th17 cells infiltrating the CNS without differences in the percentage of Th1 cells compared with animals transferred with wild-type DCs. Our findings demonstrate that by contributing to CD4(+) T cell activation and differentiation to Th17 phenotype, D5R expressed on DCs is able to modulate the development of an autoimmune response in vivo.


Paraquat Poisoning: Analysis of an Uncommon Cause of Fatal Poisoning from Manipal, South India.
Morbidity and mortality related to acute poisoning is a serious health concern worldwide. Paraquat is known to be responsible for a number of acute poisonings in south India. The study aims at presenting the various aspects of paraquat poisoning that include patient profile, clinical presentation, end-organ complications, and observations at autopsy. The present registry-based retrospective research was conducted in a tertiary care teaching hospital in south India. All the confirmed cases of paraquat poisoning were included in the present study. The postmortem and hospital records of these patients were retrieved and relevant information was collected and analyzed. Paraquat poisonings constituted 14.4% of the total poisoning fatalities during the study period. Equal number of males and females were observed in the present study. The victims were aged between 17 and 65 years (mean ± SD = 30.2 ± 13.1 years). Manner of death was suicidal in 92.9% cases. Common presenting symptoms after ingestion of paraquat included vomiting, followed by difficulty in breathing. In the present series, overall survival post paraquat consumption ranged between 10 h and 25 days. Half of the victims died within 2 days of consumption of poison. The underlying cause of death included acute renal failure (ARF), adult respiratory distress syndrome (ARDS), multiorgan failure (MOF), acute liver failure, etc., In all the cases, brain was congested and edematous, and visceral organs showed marked congestion at autopsy. Lungs were congested with marked edema in 10 cases. It is recommended that the availability of this highly toxic substance be restricted so as to prevent its misuse as a method of suicide.


Predicting the likely response of data-poor ecosystems to climate change using space-for-time substitution across domains.
Predicting ecological response to climate change is often limited by a lack of relevant local data from which directly applicable mechanistic models can be developed. This limits predictions to qualitative assessments or simplistic rules of thumb in data-poor regions, making management of the relevant systems difficult. We demonstrate a method for developing quantitative predictions of ecological response in data-poor ecosystems based on a space-for-time substitution, using distant, well-studied systems across an inherent climatic gradient to predict ecological response. Changes in biophysical data across the spatial gradient are used to generate quantitative hypotheses of temporal ecological responses that are then tested in a target region. Transferability of predictions among distant locations, the novel outcome of this method, is demonstrated via simple quantitative relationships that identify direct and indirect impacts of climate change on physical, chemical and ecological variables using commonly available data sources. Based on a limited subset of data, these relationships were demonstrably plausible in similar yet distant (>2000 km) ecosystems. Quantitative forecasts of ecological change based on climate-ecosystem relationships from distant regions provides a basis for research planning and informed management decisions, especially in the many ecosystems for which there are few data. This application of gradient studies across domains - to investigate ecological response to climate change - allows for the quantification of effects on potentially numerous, interacting and complex ecosystem components and how they may vary, especially over long time periods (e.g. decades). These quantitative and integrated long-term predictions will be of significant value to natural resource practitioners attempting to manage data-poor ecosystems to prevent or limit the loss of ecological value. The method is likely to be applicable to many ecosystem types, providing a robust scientific basis for estimating likely impacts of future climate change in ecosystems where no such method currently exists.


Preliminary analysis of phosphorus flow in Hue Citadel.
Characteristics of waste and wastewater management can affect material flows. Our research investigates the management of waste and wastewater in urban areas of developing countries and its effects on phosphorus flow based on a case study in Hue Citadel, Hue, Vietnam. One hundred households were interviewed to gain insight into domestic waste and wastewater management together with secondary data collection. Next, a phosphorus flow model was developed to quantify the phosphorus input and output in the area. The results showed that almost all wastewater generated in Hue Citadel was eventually discharged into water bodies and to the ground/groundwater. This led to most of the phosphorus output flowing into water bodies (41.2 kg P/(ha year)) and ground/groundwater (25.3 kg P/(ha year)). Sewage from the sewer system was the largest source of phosphorus loading into water bodies, while effluent from on-site sanitation systems was responsible for a major portion of phosphorus into the ground/groundwater. This elevated phosphorus loading is a serious issue in considering surface water and groundwater protection.


Displaced Supracondylar Humerus Fractures in Children - Are They All Identical?
Introduction: This study aims to ascertain if there are any differences in supracondylar fractures between children under seven years of age and those above 7 years of age. Materials and Methods: All cases of displaced humerus supracondylar fractures that required surgical stabilization were identified and retrospectively reviewed. Demographic data, mode of injury, associated neurovascular injuries and details of surgery performed were obtained from clinical records. The Gartland classification and the extent of comminution of fractures were also documented from review of radiographs. Results: One hundred and twelve children were included in this study, of whom 61 (54.46%) were younger than seven years of age while 51 (45.5%) were aged seven years or older. Children aged seven or older had a greater incidence of associated neurological deficit at presentation (p=0.046). Of the six patients with nerve injury in the older age group, one patient (16.7%) had a radial nerve injury, two patients (33.3%) had ulnar nerve injuries while another two patients (33.3%) had median nerve injuries. There was one patient (16.7%) with both median and ulnar nerve injuries. Comminuted fractures were also more common in the older children (p=0.004). No significant differences were demonstrated between the groups with regard to age, gender and mechanism of injury, laterality, incidence of open fracture, vascular injuries and operative time. Conclusion: Children aged seven years or older who sustain supracondylar humeral fractures tend to get more comminuted fractures. There is also a higher incidence of associated neurological injury. These cases must be carefully examined for at presentation and parents need to be appropriately counselled about them.


Why colorectal screening fails to achieve the uptake rates of breast and cervical cancer screening: a comparative qualitative study.
In Scotland, the uptake of clinic-based breast (72%) and cervical (77%) screening is higher than home-based colorectal screening (~60%). To inform new approaches to increase uptake of colorectal screening, we compared the perceptions of colorectal screening among women with different screening histories. We purposively sampled women with different screening histories to invite to semistructured interviews: (1) participated in all; (2) participated in breast and cervical but not colorectal ('colorectal-specific non-participants'); (3) participated in none. To identify the sample we linked the data for all women eligible for all three screening programmes in Glasgow, Scotland (aged 51-64 years; n=68 324). Interviews covered perceptions of cancer, screening and screening decisions. Framework method was used for analysis. Of the 2924 women invited, 86 expressed an interest, and 59 were interviewed. The three groups' perceptions differed, with the colorectal-specific non-participants expressing that: (1) treatment for colorectal cancer is more severe than for breast or cervical cancer; (2) colorectal symptoms are easier to self-detect than breast or cervical symptoms; (3) they worried about completing the test incorrectly; and (4) the colorectal test could be more easily delayed or forgotten than breast or cervical screening. Our comparative approach suggested targets for future interventions to increase colorectal screening uptake including: (1) reducing fear of colorectal cancer treatments; (2) increasing awareness that screening is for the asymptomatic; (3) increasing confidence to self-complete the test; and (4) providing a suggested deadline and/or additional reminders.


Near-field observation of light propagation in nanocoax waveguides.
We report the observation of propagating modes of visible and near infrared light in nanoscale coaxial (metal-dielectric-metal) structures, using near-field scanning optical microscopy. Together with numerical calculations, we show that the propagated modes have different nature depending on the excitation wavelength, i.e., plasmonic TE11 and TE21 modes in the near infrared and photonic TE31, TE41 and TM11 modes in the visible. Far field transmission out of the nanocoaxes is dominated by the superposition of Fabry-Perot cavity modes resonating in the structures, consistent with theory. Such coaxial optical waveguides may be useful for future nanoscale photonic systems.


Diets and drugs for weight loss and health in obesity - An update.
Numerous combinations of diets and pharmacological agents, including lifestyle changes, have been launched to treat obesity. There are still ambiguities regarding the efficacies of different approaches despite many clinical trials and the use of animal models to study physiological mechanisms in weight management and obesity comorbidities, Here, we present an update on promising diets and pharmacological aids. Literature published after the year 2005 was searched in PubMed, Medline and Google scholar. Among recommended diets are low-fat (LF) and low-carbohydrate (LC) diets, in addition to the Mediterranean diet and the intermittent fasting approach, all of which presumably being optimized by adequate contents of dietary fibers. A basic point for weight loss is to adopt a diet that creates a permanently negative and acceptable energy balance, and prolonged dietary adherence is a crucial factor. As for pharmacological aids, obese patients with type 2 diabetes or insulin resistance seem to benefit from LC diet combined with a GLP-1 agonist, e.g. semaglutide, which may improve glycemic control, stimulate satiety, and suppress appetite. The lipase inhibitor orlistat is still used to maintain a low-fat approach, which may be favorable e.g. in hypercholesterolemia. The bupropion-naltrexone-combination appears promising for interruption of the vicious cycle of addictive over-eating. Successful weight loss seems to improve almost all biomarkers of obesity comorbidities. Until more support for specific strategies is available, clinicians should recommend an adapted lifestyle, and when necessary, a drug combination tailored to individual needs and comorbidities. Different diets may change hormonal secretion, gut-brain signaling, and influence hunger, satiety and energy expenditure. Further research is needed to clarify mechanisms and how such knowledge can be used in weight management.


Localization-associated immune phenotypes of clonally expanded tumor-infiltrating T cells and distribution of their target antigens in rectal cancer.
The degree and type of T cell infiltration influence rectal cancer prognosis regardless of classical tumor staging. We asked whether clonal expansion and tumor infiltration are restricted to selected-phenotype T cells; which clones are accessible in peripheral blood; and what the spatial distribution of their target antigens is. From five rectal cancer patients, we isolated paired tumor-infiltrating T cells (TILs) and T cells from unaffected rectum mucosa (TUM) using 13-parameter FACS single cell index sorting. TCRαβ sequences, cytokine, and transcription factor expression were determined with single cell sequencing. TILs and TUM occupied distinct phenotype compartments and clonal expansion predominantly occurred within CD8+ T cells. Expanded TIL clones identified by paired TCRαβ sequencing and exclusively detectable in the tumor showed characteristic PD-1 and TIM-3 expression. TCRβ repertoire sequencing identified 49 out of 149 expanded TIL clones circulating in peripheral blood and 41 (84%) of these were PD-1- TIM-3-. To determine whether clonal expansion of predominantly tumor-infiltrating T cell clones was driven by antigens uniquely presented in tumor tissue, selected TCRs were reconstructed and incubated with cells isolated from corresponding tumor or unaffected mucosa. The majority of clones exclusively detected in the tumor recognized antigen at both sites. In summary, rectal cancer is infiltrated with expanded distinct-phenotype T cell clones that either i) predominantly infiltrate the tumor, ii) predominantly infiltrate the unaffected mucosa, or iii) overlap between tumor, unaffected mucosa, and peripheral blood. However, the target antigens of predominantly tumor-infiltrating TIL clones do not appear to be restricted to tumor tissue.


Investigation of concentrically and eccentrically layered droplets by light scattering.
Two pairs of immiscible liquid compounds are chosen to prepare levitated layered droplets with and without density difference between core and layer phases. The droplets are examined by light scattering along two orthogonal directions. A layered droplet without phase density difference is unambiguously identified as a concentric sphere by matching the observed scattering spectra with those calculated from the Aden-Kerker extension of Mie theory. For layered droplets with phase density difference, only the scattering spectrum from one of the scattering directions can be matched theoretically. These observations suggest that a static layered droplet is predominantly eccentric even though the embedded core is large by volume, as predicted from fluid mechanics. The consistency of the light-scattering characterization with the diffusion theory governing the evaporation of concentrically and eccentrically layered droplets is also established.


Investigation of sonar transponders for offshore wind farms: modeling approach, experimental setup, and results.
The installation of offshore wind farms in the German Exclusive Economic Zone requires the deployment of sonar transponders to prevent collisions with submarines. The general requirements for these systems have been previously worked out by the Research Department for Underwater Acoustics and Marine Geophysics of the Bundeswehr. In this article, the major results of the research project "Investigation of Sonar Transponders for Offshore Wind Farms" are presented. For theoretical investigations a hybrid approach was implemented using the boundary element method to calculate the source directivity and a three-dimensional ray-tracing algorithm to estimate the transmission loss. The angle-dependence of the sound field as well as the weather-dependence of the transmission loss are compared to experimental results gathered at the offshore wind farm alpha ventus, located 45 km north of the island Borkum. While theoretical and experimental results are in general agreement, the implemented model slightly underestimates scattering at the rough sea surface. It is found that the source level of 200 dB re 1 μPa at 1 m is adequate to satisfy the detectability of the warning sequence at distances up to 2 NM (≈3.7 km) within a horizontal sector of ±60° if realistic assumptions about signal-processing and noise are made. An arrangement to enlarge the angular coverage is discussed.


Split spectrum: a multi-channel approach to elastic optical networking.
This paper introduces Split Spectrum, which enhances elastic optical networking by splitting a bulk traffic demand into multiple channels, when a single-channel transmission is prohibited by distance or spectrum availability. We performed transmission simulations to determine the maximum reach as a function of modulation format (dual polarization BPSK, QPSK, 16QAM), baud-rate (from 5 to 28 GBd), and number of ROADMs, for a Nyquist WDM super-channel with subcarrier spacing equal to 1.2 × baud-rate. Performance evaluation on two representative topologies shows that, compared to the previously proposed elastic optical networking, Split Spectrum doubles the zero-blocking load and achieves 100% higher network spectral efficiency at zero-blocking loads as a result of extended transmission distance and efficient utilization of spectrum fragments.


Immune alterations in geriatric mice dosed subacutely with diethylstilbestrol (DES).
Exposure to both physiological and pharmacological doses of estrogenic compounds has been reported to alter immunologic responses in humans as well as in developmental and adult murine models. Despite the current therapeutic use of potent estrogens, including diethylstilbestrol (DES), in geriatric human disorders, elucidation of the effects of these agents on the aged immune system is limited. The present report describes highly significant alterations in the thymus and bone marrow of aged mice (21 +/- 1 months) exposed subacutely to DES. Severe thymic hypocellularity developed in treated mice following five consecutive days of intraperitoneal injection with 1.5 or 6.0 mg kg(-1) DES. Cell maturation within the thymus was also affected, as indicated by a significant decrease in CD4+8+ cells and a concomitant increase in CD4-8- cells. Cellularity of the bone marow was unchanged by DES. However, significant changes were observed in percentages of bone marrow cells expressing surface antigens CD45 (common leukocyte lineage), Mac-1 (macrophage lineage) and CD45R (B-lineage lymphocytes). Both percentages and total numbers of cells in the spleen expressing Thy 1.2 (T-lineage lymphocytes) were also reduced. These immune changes in geriatric mice exposed to DES were similar in direction but more severe than those reported in either young adult or perinatal models. These data may suggest a need for considering the geriatric immune system separately from other age groups when determining effects of immunosuppressive or immunotoxic compound exposure.


The Effects of Coronavirus Disease 2019 on Pediatric Anesthesiologists: A Survey of the Members of the Society for Pediatric Anesthesia.
The coronavirus disease 2019 (COVID-19) pandemic has affected the personal and professional lives of all health care workers. Anesthesiologists frequently perform virus-aerosolizing procedures (eg, intubation and extubation) that place them at increased risk of infection. We sought to determine how the initial COVID-19 outbreak affected members of the Society for Pediatric Anesthesia (SPA) on both personal and professional levels. Specifically, we examined the potential effects of gender and age on personal stress, burnout, sleep deprivation, anxiety, depression, assessed job satisfaction, and explored financial impact. After receiving approval from the SPA Committees for Research and Quality and Safety and the Colorado Multiple Institutional Review Board, we e-mailed a questionnaire to all 3245 SPA members. The survey included 22 questions related to well-being and 13 questions related to effects of COVID-19 on current and future practice, finances, retirement planning, academic time and productivity, and clinical and home responsibilities. To address low initial response rates and quantify nonresponse bias, we sent a shortened follow-up survey to a randomly selected subsample (n = 100) of SPA members who did not respond to the initial survey. Response differences between the 2 cohorts were determined. A total of 561 (17%) members responded to the initial questionnaire. Because of COVID-19, 21.7% of respondents said they would change their clinical responsibilities, and 10.6% would decrease their professional working time. Women were more likely than men to anticipate a future COVID-19-related job change (odds ratio [OR] = 1.92, 95% confidence interval [CI], 1.12-2.63; P = .011), perhaps because of increased home responsibilities (OR = 2.63, 95% CI, 1.74-4.00; P < .001). Additionally, 14.2% of respondents planned to retire early, and 11.9% planned to retire later. Women and non-White respondents had higher likelihoods of burnout on univariate analysis (OR = 1.75, 95% CI, 1.06-2.94, P = .026 and OR = 1.82, 95% CI, 1.08-3.04, P = .017, respectively), and 25.1% of all respondents felt socially isolated. In addition, both changes in retirement planning and future occupational planning were strongly associated with total job satisfaction scores (both P < .001). The COVID-19 pandemic has affected the personal and professional lives of pediatric anesthesiologists, albeit not equally, as women and non-Whites have been disproportionately impacted. The pandemic has significantly affected personal finances, home responsibilities, and retirement planning; reduced clinical and academic practice time and responsibilities; and increased feelings of social isolation, stress, burnout, and depression/anxiety.


What affects public acceptance of recycled and desalinated water?
This paper identifies factors that are associated with higher levels of public acceptance for recycled and desalinated water. For the first time, a wide range of hypothesized factors, both of socio-demographic and psychographic nature, are included simultaneously. The key results, based on a survey study of about 3000 respondents are that: (1) drivers of the stated likelihood of using desalinated water differ somewhat from drivers of the stated likelihood of using recycled water; (2) positive perceptions of, and knowledge about, the respective water source are key drivers for the stated likelihood of usage; and (3) awareness of water scarcity, as well as prior experience with using water from alternative sources, increases the stated likelihood of use. Practical recommendations for public policy makers, such as key messages to be communicated to the public, are derived.


Upright posture and postprandial hypotension in elderly persons.
Syncope and falls are common in elderly persons and often result from the interaction of multiple clinical abnormalities. Both orthostatic hypotension and postprandial hypotension increase in prevalence with age. To determine whether meal ingestion enhances orthostatic hypotension in elderly persons. Controlled paired comparison. Clinical research center. 50 functionally independent elderly persons recruited from local senior centers (n = 47) and from patients hospitalized with an unexplained fall or syncope (n = 3) (mean age, 78 years [range, 61 to 96 years]). Twenty-five participants (50%) were taking antihypertensive medication. Sequential head-up tilt-table testing at 60 degrees was performed before and 30 minutes after ingestion of a standardized warm liquid meal that was high in carbohydrates. Heart rate and blood pressure were continuously monitored. Meal ingestion (P < 0.01) and time spent upright (P < 0.001) were significantly associated with systolic blood pressure, but no significant interaction was found between meal ingestion and time spent upright (P > 0.2). These findings suggest that the association between meal ingestion and head-up tilt-table testing were additive and not synergistic. However, the proportion of participants with symptomatic hypotension increased during head-up tilt-table testing after meal ingestion (12% during preprandial testing and 22% during postprandial testing). Symptomatic hypotension tended to occur more often and sooner after meal ingestion than before meal ingestion (P = 0.03). Meal ingestion and head-up tilt-table testing are associated with increasing occurrences of symptomatic hypotension. After meal ingestion and head-up tilt-table testing, 22% of functionally independent elderly persons had symptomatic hypotension.


Biofilm formation by Staphylococcus epidermidis on peritoneal dialysis catheters and the effects of extracellular products from Pseudomonas aeruginosa.
Biofilm formation by Staphylococcus epidermidis is a cause of infections related to peritoneal dialysis (PD). We have used a PD catheter flow-cell model in combination with confocal scanning laser microscopy and atomic force microscopy to study biofilm formation by S. epidermidis. Adherence to serum-coated catheters was four times greater than to uncoated ones, suggesting that S. epidermidis binds to serum proteins on the catheter surface. Pseudomonas aeruginosa biofilm supernatant interfered with the formation of a serum protein coat thereby reducing the capacity for biofilm formation in S. epidermidis. Supernatants from ΔpelA, ΔpslBCD and ΔrhlAB strains of P. aeruginosa showed no differences from the wild-type supernatant indicating that the effect on serum coat formation was not due to rhamnolipids or the PelA and PslBCD polysaccharides. Supernatant from P. aeruginosa also dispersed established S. epidermidis biofilms. Supernatants lacking PelA or PslBCD showed no differences from the wild type but that from a ΔrhlAB strain, showed reduced, but not abolished, capacity for dispersal. This suggests that rhamnolipids are involved but not wholly responsible for the effect. Thus, supernatants from P. aeruginosa contain promising substances for the prevention and treatment of biofilm infections, although further work is required to identity more active components.


Prognostic Value of Biochemical Recurrence Following Treatment with Curative Intent for Prostate Cancer: A Systematic Review.
In men with prostate cancer (PCa) treated with curative intent, controversy exists regarding the impact of biochemical recurrence (BCR) on oncological outcomes. To perform a systematic review of the existing literature on BCR after treatment with curative intent for nonmetastatic PCa. Objective 1 is to investigate whether oncological outcomes differ between patients with or without BCR. Objective 2 is to study which clinical factors and tumor features in patients with BCR have an independent prognostic impact on oncological outcomes. Medline, Medline In-Process, Embase, and the Cochrane Central Register of Controlled Trials were searched. For objective 1, prospective and retrospective studies comparing survival outcomes of patients with or without BCR following radical prostatectomy (RP) or radical radiotherapy (RT) were included. For objective 2, all studies with at least 100 participants and reporting on prognostic patient and tumor characteristics in patients with BCR were included. Risk-of-bias and confounding assessments were performed according to the Quality in Prognosis Studies tool. Both a narrative synthesis and a meta-analysis were undertaken. Overall, 77 studies were included for analysis, of which 14 addressed objective 1, recruiting 20 406 patients. Objective 2 was addressed by 71 studies with 29 057, 11 301, and 4272 patients undergoing RP, RT, and a mixed population (mix of patients undergoing RP or RT as primary treatment), respectively. There was a low risk of bias for study participation, confounders, and statistical analysis. For most studies, attrition bias, and prognostic and outcome measurements were not clearly reported. BCR was associated with worse survival rates, mainly in patients with short prostate-specific antigen doubling time (PSA-DT) and a high final Gleason score after RP, or a short interval to biochemical failure (IBF) after RT and a high biopsy Gleason score. BCR has an impact on survival, but this effect appears to be limited to a subgroup of patients with specific clinical risk factors. Short PSA-DT and a high final Gleason score after RP, and a short IBF after RT and a high biopsy Gleason score are the main factors that have a negative impact on survival. These factors may form the basis of new BCR risk stratification (European Association of Urology BCR Risk Groups), which needs to be validated formally. This review looks at the risk of death in men who shows rising prostate-specific antigen (PSA) in the blood test performed after curative surgery or radiotherapy. For many men, rising PSA does not mean that they are at a high risk of death from prostate cancer in the longer term. Men with PSA that rises shortly after they were treated with radiotherapy or rapidly rising PSA after surgery and a high tumor grade for both treatment modalities are at the highest risk of death. These factors may form the basis of new risk stratification (European Association of Urology biochemical recurrence Risk Groups), which needs to be validated formally.


Anal sex among HIV-seronegative women at high risk of HIV exposure. The HIVNET Vaccine Preparedness Study 2 Protocol Team.
To assess the prevalence and the sociodemographic and behavioral correlates of anal sex in a cohort of HIV-seronegative U.S. women at high risk of HIV exposure, we administered a risk assessment using audio computer-assisted self-interview (A-CASI). Of 1268 sexually active women, 432 (32%) reported anal sex in the previous 6 months. Compared with women who did not report anal sex, those who did had more unprotected vaginal sex (median of 11 versus 7 episodes; p <. 001) and a higher proportion of unprotected sexual (vaginal plus anal) episodes (median of 0.90 versus 0.81; p =.01). Anal sex was reported by higher proportions of women who did not always use condoms, who used crack in the past year, who were </=35 years of age, with no formal education beyond high school, who had had a diagnosed sexually transmitted disease in the previous year, a primary male sex partner, and a male sex partner with a history of injecting use. Women were more likely to report anal sex by A-CASI than during interviewer-administered risk assessments (odds ratio [OR], 9.00; 95% confidence interval [CI], 1.14-71.0). A less biased method of ascertainment may account for the large proportion of women reporting anal sex. Given increased vaginal risk among women reporting anal sex, the relative importance of anal sex in heterosexual transmission merits further study. Behavioral and biomedical prevention strategies effective for anal as well as vaginal sex are needed.


Application of electronic circular dichroism in the study of supramolecular systems.
Chiral supramolecular architectures constitute crucial structural and functional elements in living systems and have been long mimicked by chemists to synthesize new artificial systems endowed with desired properties and functions. Among several techniques to study noncovalent chiral assemblies or aggregates, electronic circular dichroism (ECD) plays a key role because many mechanisms responsible for the appearance of ECD bands occur through space, and therefore are intrinsically sensitive to intermolecular interactions, from short to long-range. The aim of this tutorial review is to emphasize the different kinds of information which can be obtained specifically when chiral supramolecular species are characterized by means of ECD spectroscopy. We will survey several typical applications of ECD in the context of supramolecular chemistry, ranging from the simple detection of chiral aggregates or complexes, to the definition of stoichiometric ratios between the partners, the derivation of thermodynamic and kinetic parameters such as binding and rate constants, and ultimately to the refinement of the most plausible structure of the supramolecular species.