BDNF-induced LTP is associated with rapid Arc/Arg3.1-dependent enhancement in adult hippocampal neurogenesis.
Adult neurogenesis in the hippocampus is a remarkable phenomenon involved in various aspects of learning and memory as well as disease pathophysiology. Brain-derived neurotrophic factor (BDNF) represents a major player in the regulation of this unique form of neuroplasticity, yet the mechanisms underlying its pro-neurogenic actions remain unclear. Here, we examined the effects associated with brief (25 min), unilateral infusion of BDNF in the rat dentate gyrus. Acute BDNF infusion induced long-term potentiation (LTP) of medial perforant path-evoked synaptic transmission and, concomitantly, enhanced hippocampal neurogenesis bilaterally, reflected by increased dentate gyrus BrdU + cell numbers. Importantly, inhibition of activity-regulated cytoskeleton-associated protein (Arc/Arg3.1) translation through local, unilateral infusion of anti-sense oligodeoxynucleotides (ArcAS) prior to BDNF infusion blocked both BDNF-LTP induction and the associated pro-neurogenic effects. Notably, basal rates of proliferation and newborn cell survival were unaltered in homozygous Arc/Arg3.1 knockout mice. Taken together these findings link the pro-neurogenic effects of acute BDNF infusion to induction of Arc/Arg3.1-dependent LTP in the adult rodent dentate gyrus.


Fast iterative tomographic wavefront estimation with recursive Toeplitz reconstructor structure for large-scale systems.
Tomographic wavefront reconstruction is the main computational bottleneck to realize real-time correction for turbulence-induced wavefront aberrations in future laser-assisted tomographic adaptive-optics (AO) systems for ground-based giant segmented mirror telescopes because of its unprecedented number of degrees of freedom, N, i.e., the number of measurements from wavefront sensors. In this paper, we provide an efficient implementation of the minimum-mean-square error (MMSE) tomographic wavefront reconstruction, which is mainly useful for some classes of AO systems not requiring multi-conjugation, such as laser-tomographic AO, multi-object AO, and ground-layer AO systems, but is also applicable to multi-conjugate AO systems. This work expands that by Conan [Proc. SPIE9148, 91480R (2014)PSISDG0277-786X10.1117/12.2054472] to the multi-wavefront tomographic case using natural and laser guide stars. The new implementation exploits the Toeplitz structure of covariance matrices used in an MMSE reconstructor, which leads to an overall O(N log N) real-time complexity compared with O(N2) of the original implementation using straight vector-matrix multiplication. We show that the Toeplitz-based algorithm leads to 60 nm rms wavefront error improvement for the European Extremely Large Telescope laser-tomography AO system over a well-known sparse-based tomographic reconstruction; however, the number of iterations required for suitable performance is still beyond what a real-time system can accommodate to keep up with the time-varying turbulence.


Graduate status and age at entry to medical school as predictors of doctors' choice of long-term career.
To determine whether graduate entry to medical school, taking an intercalated degree during medical school, and age at entry to medical school are related to choice of eventual career. Postal questionnaires. United Kingdom (UK). All doctors who qualified in the UK in 1993 or 1996. We analysed whether graduate status and age on entry to medical school, and taking an intercalated degree during medical school, were predictors of the choice of eventual career, adjusting for differences by sex, year of qualification and medical school. General practice was the career choice of 27.0% (79/293) of graduate entrants and 21.6% (1095/5073) of non-graduate entrants, a difference of borderline significance (P=0.04). Of the non-graduate entrants, general practice was the career choice of 15.3% (319/2081) of doctors who took an intercalated degree and 25.9% (776/2992) of doctors who did not (P < 0.001). Within the hospital specialties, those who took an intercalated degree were more likely than others to choose the hospital medical specialties or pathology. Age alone was not a predictor for choice of any area of practice. There was no evidence of an association between age at entry to medical school and choice of eventual career. Graduates at entry to medical school were a little more likely than non-graduates to choose general practice but the relationship was not a strong one. In these respects, changing the entry profile of medical students is unlikely to result in major shifts of career choice towards general practice.


Improving patient knowledge and safe use of opioids: a randomized controlled trial.
The use of opioid analgesics in the United States has significantly increased in recent years. However, there is minimal consensus on what discharge counseling should accompany these high-risk prescriptions and large variations in what is done in practice. The objective of this study was to evaluate the effect of a dual-modality (written and spoken) literacy-appropriate educational strategy on patients' knowledge of and safe use of opioid analgesics. This was a prospective, randomized controlled trial. Consecutive discharged patients at an urban academic ED (>88,000 visits) with new prescriptions for hydrocodone-acetaminophen were enrolled. Patients were randomized to receive either usual care or the educational intervention. The educational intervention was a one-page information sheet about hydrocodone-acetaminophen, which was both given to the patients and read aloud by the research assistant (nonblinded). Follow-up phone calls were conducted 4 to 7 days after the visit to assess patient knowledge about the medication and self-report of activities associated with safety of use (e.g., double-dipping with acetaminophen, storage, use with alcohol or while driving). A total of 274 patients were enrolled; 210 completed follow-up (110 usual care and 100 intervention). No significant differences in baseline characteristics emerged between the study arms; 42% were male, and 51% were white, with a median age of 43 years. Half of patients had non-back pain orthopedic injuries (49.5%). On follow-up, overall knowledge was poor, with only 28% able to name both active ingredients in the medication. The intervention group had better knowledge of precautions related to taking additional acetaminophen (usual care 18.2%, 95% confidence interval [CI] = 10.9% to 25.5% vs. intervention 38%, 95% CI = 28.3% to 47.7%; difference = 27.6, 95% CI of difference = 21.5 to 33.7) and knowledge of side effects (usual care median = 1, interquartile range [IQR] 0 to 2 vs. intervention median = 2, IQR = 1 to 2; p < 0.0001). Additionally, those who received the intervention were less likely to have reported driving within 6 hours after taking hydrocodone (usual care 13.6%, 95% CI = 7.2% to 20% vs. intervention 3%, 95% CI = -0.3% to 6.3%; difference = 10.6, 95% CI of difference = 3.4 to 17.9). There was no difference between groups related to knowledge about drinking alcohol while taking hydrocodone (overall 18.1%) or knowledge that the opioid could be addictive (overall 72.4%). This simple strategy improved several, but not all, aspects of patient knowledge and resulted in fewer patients in the intervention arm driving while taking hydrocodone. Integration of a patient education document into conversations about opioids holds promise for improving patient knowledge about these high-risk medications.


A New Framework for Urban Ecology: An Integration of Proximate and Ultimate Responses to Anthropogenic Change.
As urban areas continue to grow, understanding how species respond and adapt to urban habitats is becoming increasingly important. Knowledge of the mechanisms behind observed phenotypic changes of urban-dwelling animals will enable us to better evaluate the impact of urbanization on current and future generations of wildlife and predict how animals respond to novel environments. Recently, urban ecology has emerged not only as a means of understanding organismal adaptation but also as a framework for exploring mechanisms mediating evolutionary phenomena. Here, we have identified four important research topics that will advance the field of urban ecology and shed light on the proximate and ultimate causes of the phenotypic differences commonly seen among species and populations that vary in their responses to urbanization. First, we address the ecological and socio-economic factors that characterize cities, how they might interact with each other, and how they affect urban species. Second, we ask which are the proximate mechanisms underlying the emergence over time of novel traits in urban organisms, focusing on developmental effects. Third, we emphasize the importance of understanding the ultimate causations that link phenotypic shifts to function. This question highlights the need to quantify the strength and direction of selection that urban individuals are exposed to, and whether the phenotypic shifts associated with life in the city are adaptive. Lastly, we stress the need to translate how individual-level responses scale up to population dynamics. Understanding the mechanistic underpinnings of variation among populations and species in their responses to urbanization will unravel species resilience to environmental perturbation, which will facilitate predictive models for sustainability and development of green cities that maintain or even increase urban biodiversity and wildlife health and wellbeing.


Statins in Stroke Prevention: Present and Future.
Over the last decades, the reduction of the mortality and morbidity of stroke has been a high- priority objective worldwide. Statins, or 3-hydroxy-3- methylglutaryl coenzyme A (HMG- CoA) reductase inhibitors, have emerged as the predominant preventive strat egy to tackle the worldwide stroke burden. Currently, statins are considered the most important advance in stroke prevention since the introduction of aspirin and antihypertensive treatments. In this paper we review the current evidence regarding the role of statins in the stroke prevention and future directions in this field. A meta-analysis of random ised trials of statins has shown that each 1 mmol/L (39 mg/dL) decrease in low-density lipoprotein cholesterol, equates to a reduction in relative risk for stroke of 21.1%. Statins are now recommended for the primary prevention of ischemic stroke in patients estimated to have a high 10-year risk for cardiovascular events. Nevertheless, until recently there was little evidence that statin therapy reduced the risk of stroke recurrence. The SPARCL, published in 2006, was the first trial to show the benefits of statin therapy in preventing recurrent stroke. Now we know that statins reduce the risk of stroke recurrence by 12-16% and statins are recommended among patients with ischemic stroke or TIA presumed to be of atherosclerotic origin or with other comorbid atherosclerotic cardiovascular disease. Traditionally, there has been no clear data demonstrating that adding other lipid-modifying drugs to statins results in a further decrease in stroke or other cardiovascular event, but now things have changed and future directions include combinations with ezetimibe and new treatments such as PCSK9 inhibitors. Only time will tell the real roll of these new promising non-statin lipidmodifying therapies on stroke prevention.


The activities of hospital nursing unit managers and quality of patient care in South African hospitals: a paradox?
Improving the quality of health care is central to the proposed health care reforms in South Africa. Nursing unit managers play a key role in coordinating patient care activities and in ensuring quality care in hospitals. This paper examines whether the activities of nursing unit managers facilitate the provision of quality patient care in South African hospitals. During 2011, a cross-sectional, descriptive study was conducted in nine randomly selected hospitals (six public, three private) in two South African provinces. In each hospital, one of each of the medical, surgical, paediatric, and maternity units was selected (n=36). Following informed consent, each unit manager was observed for a period of 2 hours on the survey day and the activities recorded on a minute-by-minute basis. The activities were entered into Microsoft Excel, coded into categories, and analysed according to the time spent on activities in each category. The observation data were complemented by semi-structured interviews with the unit managers who were asked to recall their activities on the day preceding the interview. The interviews were analysed using thematic content analysis. The study found that nursing unit managers spent 25.8% of their time on direct patient care, 16% on hospital administration, 14% on patient administration, 3.6% on education, 13.4% on support and communication, 3.9% on managing stock and equipment, 11.5% on staff management, and 11.8% on miscellaneous activities. There were also numerous interruptions and distractions. The semi-structured interviews revealed concordance between unit managers' recall of the time spent on patient care, but a marked inflation of their perceived time spent on hospital administration. The creation of an enabling practice environment, supportive executive management, and continuing professional development are needed to enable nursing managers to lead the provision of consistent and high-quality patient care.


Enlarged perivascular spaces and cognition: A meta-analysis of 5 population-based studies.
To investigate the association of enlarged perivascular spaces (ePVS) with cognition in elderly without dementia. We included 5 studies from the Uniform Neuro-Imaging of Virchow-Robin Space Enlargement (UNIVRSE) consortium, namely the Austrian Stroke Prevention Family Study, Study of Health in Pomerania, Rotterdam Study, Epidemiology of Dementia in Singapore study, and Risk Index for Subclinical Brain Lesions in Hong Kong study. ePVS were counted in 4 regions (mesencephalon, hippocampus, basal ganglia, and centrum semiovale) with harmonized rating across studies. Mini-Mental State Examination (MMSE) and general fluid cognitive ability factor (G-factor) were used to assess cognitive function. For each study, a linear regression model was performed to estimate the effect of ePVS on MMSE and G-factor. Estimates were pooled across studies with the use of inverse variance meta-analysis with fixed- or random-effect models when appropriate. The final sample size consisted of 3,575 persons (age range 63.4-73.2 years, 50.6% women). Total ePVS counts were not significantly associated with MMSE score (mean difference per ePVS score increase 0.001, 95% confidence interval [CI] -0.007 to 0.008, p = 0.885) or G-factor (mean difference per ePVS score increase 0.002, 95% CI -0.001 to 0.006, p = 0.148) in age-, sex-, and education-adjusted models. Adjustments for cardiovascular risk factors and MRI markers did not change the results. Repeating the analyses with region-specific ePVS rendered similar results. In this study, we found that ePVS counts were not associated with cognitive dysfunction in the general population. Future studies with longitudinal designs are warranted to examine whether ePVS contribute to cognitive decline.


Using avatars in weight management settings: A systematic review.
Obesity interventions rely predominantly on managing dietary intake and/or increasing physical activity but sustained adherence to behavioural regimens is often poor. Avatar technology is well established within the computer gaming industry and evidence suggests that virtual representations of self may impact real-world behaviour, acting as a catalyst for sustained weight loss behaviour modification. However, the effectiveness of avatar technology in promoting weight loss is unclear. We aimed to assess the quantity and quality of empirical support for the use of avatar technologies in adult weight loss interventions. A systematic review of empirical studies was undertaken. The key objectives were to determine if: (i) the inclusion of avatar technology leads to greater weight loss achievement compared to routine intervention; and (ii) whether weight loss achievement is improved by avatar personalisation (avatar visually reflects self). We identified 6 papers that reported weight loss data. Avatar-based interventions for weight loss management were found to be effective in the short (4-6 weeks) and medium (3-6 months) term and improved weight loss maintenance in the long term (12 months). Only 2 papers included avatar personalisation, but results suggested there may be some added motivational benefit. The current evidence supports that avatars may positively impact weight loss achievement and improve motivation. However, with only 6 papers identified the evidence base is limited and therefore findings need to be interpreted with caution.


Collective Behaviour in Video Viewing: A Thermodynamic Analysis of Gaze Position.
Videos and commercials produced for large audiences can elicit mixed opinions. We wondered whether this diversity is also reflected in the way individuals watch the videos. To answer this question, we presented 65 commercials with high production value to 25 individuals while recording their eye movements, and asked them to provide preference ratings for each video. We find that gaze positions for the most popular videos are highly correlated. To explain the correlations of eye movements, we model them as "interactions" between individuals. A thermodynamic analysis of these interactions shows that they approach a "critical" point such that any stronger interaction would put all viewers into lock-step and any weaker interaction would fully randomise patterns. At this critical point, groups with similar collective behaviour in viewing patterns emerge while maintaining diversity between groups. Our results suggest that popularity of videos is already evident in the way we look at them, and that we maintain diversity in viewing behaviour even as distinct patterns of groups emerge. Our results can be used to predict popularity of videos and commercials at the population level from the collective behaviour of the eye movements of a few viewers.


A charge neutral, size tuneable polymersome capable of high biological encapsulation efficiency and cell permeation.
The field of therapeutics is evolving to include a greater proportion of higher molecular weight, hydrophilic biological compounds. To cater for this new era in healthcare the concomitant development of appropriate drug delivery systems is essential to aid cellular permeation. In this manuscript we present the synthesis, characterisation and biological evaluation of a charge neutral polymersome (Ps) based drug delivery system (DDS) using an amphiphilic pegylated random copolymer. A detailed dynamic light scattering study revealed that the hydrodynamic diameter of the Ps can be tailored to a specific size simply by varying the quantities and ratios used during the preparation step. The zeta potential of this new drug delivery system was determined to be -0.095 ± 0.037 mV, the encapsulation efficiency of Fitc-CM-Dextran (4 KDa) was 70%, the uptake of Fitc-CM-Dextran by Hela cells was increased 4-fold when encapsulated within the polymersomal system. The facile preparation, high loading capacity and size tuneable nature of this Ps renders it a promising alternative to the ever growing array of currently available Ps.


Coping with digital market re-organization: How the hotel industry strategically responds to digital platform power.
How do organizations in a sector where powerful platforms have emerged cope with the new constraints and opportunities that platforms induce? A growing number of studies highlight the power of digital platforms to re-organize markets and thereby create new forms of dependence. But there are also indications that organizations are capable of countering platform power especially by demanding their regulation. This paper expands this view to investigate also strategies at the organizational level. It draws on the algorithmic game studies of strategic responses to environmental changes to study how organizations strategically respond to the rise of digital platforms. To show organizations' capacities to cope with the new digital market environment, we use a qualitative case study of the Swiss hotel sector and its reactions to so-called online travel agencies, based on interviews with hotel managers and professional representatives. We distinguish between three types of hotels-small family-run, luxury, and chain hotels, and identify three types of strategic responses: bypassing, optimizing, and mitigating. Contrary to a platform power perspective, we find some evidence for organizations' capacity to keep platforms at bay, by limiting dependence through mitigation, and platforms' reach through bypassing. Hotels also learn to "play the algorithmic game" and take advantage of platforms' technological affordances, but such strategies seem to accommodate platform power rather than countering it. Finally, we find that hotels with fewer resources (small family-run hotels) are less equipped to counter platform power, suggesting that platforms risk fostering existing hierarchies and segmentation in markets.


Dementia risk analysis using temporal event modeling on a large real-world dataset.
The objective of the study is to identify healthcare events leading to a diagnosis of dementia from a large real-world dataset. This study uses a data-driven approach to identify temporally ordered pairs and trajectories of healthcare codes in the electronic health record (EHR). This allows for discovery of novel temporal risk factors leading to an outcome of interest that may otherwise be unobvious. We identified several known (Down syndrome RR = 116.1, thiamine deficiency RR = 76.1, and Parkinson's disease RR = 41.1) and unknown (Brief psychotic disorder RR = 68.6, Toxic effect of metals RR = 40.4, and Schizoaffective disorders RR = 40.0) factors for a specific dementia diagnosis. The associations with the greatest risk for any dementia diagnosis were found to be primarily related to mental health (Brief psychotic disorder RR = 266.5, Dissociative and conversion disorders RR = 169.8), or neurologic conditions or procedures (Dystonia RR = 121.9, Lumbar Puncture RR = 119.0). Trajectory and clustering analysis identified factors related to cerebrovascular disorders, as well as diagnoses which increase the risk of toxic imbalances. The results of this study have the ability to provide valuable insights into potential patient progression towards dementia and improve recognition of patients at risk for developing dementia.


A tardigrade in Dominican amber.
Tardigrades are a diverse group of charismatic microscopic invertebrates that are best known for their ability to survive extreme conditions. Despite their long evolutionary history and global distribution in both aquatic and terrestrial environments, the tardigrade fossil record is exceedingly sparse. Molecular clocks estimate that tardigrades diverged from other panarthropod lineages before the Cambrian, but only two definitive crown-group representatives have been described to date, both from Cretaceous fossil deposits in North America. Here, we report a third fossil tardigrade from Miocene age Dominican amber. Paradoryphoribius chronocaribbeus gen. et sp. nov. is the first unambiguous fossil representative of the diverse superfamily Isohypsibioidea, as well as the first tardigrade fossil described from the Cenozoic. We propose that the patchy tardigrade fossil record can be explained by the preferential preservation of these microinvertebrates as amber inclusions, coupled with the scarcity of fossiliferous amber deposits before the Cretaceous.


Host discrimination of Mycoplasma pneumoniae proteinaceous immunogens.
The immune response of experimentally infected hamsters and human patients to Mycoplasma pneumoniae was examined by radioimmunoprecipation in conjunction with gel electrophoresis and fluorography. Both intrinsically and extrinsically labeled mycoplasma proteins were coincubated with acute and convalescent sera in a radioimmunoprecipitation assay. Two M. pneumoniae proteins were selectively precipitated by convalescent sera. These predominant immunogens were trypsin-sensitive, antibody-accessible surface proteins that co-migrate on polyacrylamide gels with proteins P1 and P2, which were previously implicated by us as mediators of cytadsorption. Anti-M. pneumoniae antiserum did not precipitate radiolabeled antigens derived from Mycoplasma orale or Mycoplasma salivarium. These data indicate that M. pneumoniae infection stimulates a specific and highly targeted host antibody response to key proteinaceous immunogens.


Glanzmann thrombasthenia in a 17-year-old Peruvian Paso mare.
A 17-year-old Peruvian Paso mare was evaluated for bilateral epistaxis that had been present for at least 3 years. The mare had mild anemia, platelet count within the reference interval, unremarkable coagulation times, and a negative Coggins test. On endoscopic examination, structural abnormalities were not observed in the nasal cavities, pharynx, larynx, trachea, or either guttural pouch, but petechiation was noted in the nasal mucosa. Additional tests revealed prolonged cutaneous bleeding time, normal concentration of von Willebrand factor antigen, an abnormal clot retraction test, and failure of plalelet aggregation in response to agonists, suggesting a functional disorder of platelets. Genetic analysis indicated the horse was homozygous for a 10-base-pair deletion that included the last 3 base pairs of exon 11 and the first 7 base pairs of intron 11 of the gene encoding glycoprotein IIb. The diagnosis was Glanzmann thrombasthenia (GT) caused by a structural defect in glycoprotein IIb. GT is an autosomal recessive disorder caused by a defect in the glycoprotein IIb-IIIa complex on platelet surfaces. Separate genes encode each glycoprotein, and mutations in either gene can result in GT. This case of GT is unique given the age of the mare at the time of diagnosis. We conclude that GT, although an inherited disorder, should be considered in horses with suspected dysfunctional platelets, regardless of age.


Treatment of Parkinson's disease with trophic factors.
Trophic factors are proteins that support and protect subpopulations of cells. A number have been reported to act on dopaminergic neurons in vitro and in vivo, making them potential therapeutic candidates for Parkinson's disease. All of these candidate factors protect dopaminergic neurons if given prior to, or with, selective neurotoxins. Fewer trophic factors, primarily glial-derived neurotrophic factor (GDNF) and its relative, neurturin (NRTN; also known as NTN), have been shown to restore function in damaged dopamine neurons after the acute effects of neurotoxins have subsided. A major barrier to clinical translation has been delivery. GDNF delivered by intracerebroventricular injection in patients was ineffective, probably because GDNF did not reach the target, the putamen, and intraputaminal infusion was ineffective, probably because of limited distribution within the putamen. A randomized clinical trial with gene therapy for NRTN is underway, in an attempt to overcome these problems with targeting and distribution. Other strategies are available to induce trophic effects in the CNS, but have not yet been the focus of human research. To date, clinical trials have focused on restoration of function (i.e., improvement of parkinsonism). Protection (i.e., slowing or halting disease progression and functional decline) might be a more robust effect of trophic agents. Laboratory research points to their effectiveness in protecting neurons and even restoring dopaminergic function after a monophasic neurotoxic insult. Utility for such compounds in patients with Parkinson's disease and ongoing loss of dopaminergic neurons remains to be proven.


Coronary hyperperfusion augments myocardial oxygen consumption.
This study was performed to test the hypothesis that increases in myocardial oxygen consumption (MVo2) and myocardial contractile function during exercise are flow limited. Studies were performed in 15 chronically instrumented normal dogs. MVo2 and regional percent systolic wall thickening were measured during control conditions and during maximal vasodilation produced by infusion of adenosine (20-75 micrograms.kg-1.min-1) or adenosine combined with nitroglycerin (0.4 micrograms.kg-1.min-1; TNG) into the left anterior descending coronary artery during a three-stage graded treadmill exercise protocol. Adenosine and adenosine plus TNG significantly increased coronary blood flow by 298 +/- 26 and 306 +/- 24%, respectively, at rest and by 134 +/- 7 and 145 +/- 9%, respectively, during the heaviest level of exercise (each P < 0.01). Adenosine and adenosine plus TNG increased MVo2 at rest, but this was associated with a parallel increase in heart rate, so that MVo2 per beat was not significantly changed. Systolic wall thickening was also not changed by hyperperfusion during resting conditions. However, MVo2 per beat was increased by 12 +/- 4% with adenosine and by 13 +/- 5% with adenosine plus TNG during moderate exercise and by 23 +/- 5% with adenosine and by 27 +/- 4% with adenosine plus TNG during the heaviest level of exercise (each P < 0.05). Systolic thickening of the full left ventricular wall did not change during hyperperfusion, but thickening in the subepicardial layer was increased by 14 +/- 3% with adenosine and 18 +/- 3% with adenosine plus TNG during the heaviest level of exercise (each P < 0.05). There was no difference in wall thickening between adenosine and adenosine plus TNG. These findings imply that the increases in MVo2 which occur during exercise are limited by coronary blood flow.


Current status of peritoneal dialysis in Korea: efforts to achieve optimal outcome.
Since its introduction in 1981, peritoneal dialysis (PD) has become firmly established as an effective mode of renal replacement therapy and serves an increasing patient population in Korea. The latest registry data indicate that about 3700 end-stage renal disease patients are maintained on chronic PD, representing 24.1% of the country's dialysis population. The majority (93.3%) of these patients are on continuous ambulatory peritoneal dialysis (CAPD) using the two-bag disconnect system, while only 3.3% are on automated PD. Under current renal reimbursement policies, most dialysis patients have to pay 20% of dialysis fees. Thus CAPD patients on 4 x 2-L daily exchanges pay about US$200 per month, not including medication and travel costs. Traditionally, most PD centers in Korea have used the "standard" prescription of 4 exchanges of 2 L of solution for most of their patients. A recent survey of 1467 patients who commenced CAPD in 1997 revealed that 84% of these patients were initially prescribed 4 x 2-L exchanges, while 12% were given a daily volume of 6 L. With this standard prescription, the percentages of Korean CAPD patients initially achieving the adequacy target of Kt/V urea > or = 2.0 and standardized creatinine clearance (SCCr) > or = 60 L/week/1.73 m2, were 74.4% and 82.1%, respectively. It is likely that, among current Korean CAPD patients, a much lower percentage will achieve the clearance targets compared to this initial outcome, but the precise data are not available. However, it is not clear whether the levels of small-solute clearance recommended for optimal PD outcomes, and proposed by the NKF-DOQI guidelines, will bring the expected benefits to Korean patients. Overall survival of Korean PD patients appears to be as good as, or even better than, that in most other countries. Recently, a single large PD center reported patient survival of 92.1%, 85.6%, 81.4%, and 67.6% at 1, 2, 3, and 5 years respectively. Other centers also reported similar outcomes. As in other countries, cardiovascular deaths predominate among Korean patients: death was due to cardiac causes in 29%, to vascular causes in 21%, and to infectious causes in 24%. Peritonitis is the most important barrier to prolonged use of CAPD in Korea, and more PD patients transfer to hemodialysis because of peritonitis than in other countries. To further reduce the morbidity and mortality of Korean PD patients, various control measures need to be implemented that can reduce or prevent peritonitis and other infectious complications. Also, to further improve long-term patient outcome, Korean nephrologists need to establish and practice optimal clearance targets in the chronic care of these patients.


IL-23 is critical for induction of arthritis, osteoclast formation, and maintenance of bone mass.
The role of IL-23 in the development of arthritis and bone metabolism was studied using systemic IL-23 exposure in adult mice via hydrodynamic delivery of IL-23 minicircle DNA in vivo and in mice genetically deficient in IL-23. Systemic IL-23 exposure induced chronic arthritis, severe bone loss, and myelopoiesis in the bone marrow and spleen, which resulted in increased osteoclast differentiation and systemic bone loss. The effect of IL-23 was partly dependent on CD4(+) T cells, IL-17A, and TNF, but could not be reproduced by overexpression of IL-17A in vivo. A key role in the IL-23-induced arthritis was made by the expansion and activity of myeloid cells. Bone marrow macrophages derived from IL-23p19(-/-) mice showed a slower maturation into osteoclasts with reduced tartrate-resistant acid phosphatase-positive cells and dentine resorption capacity in in vitro osteoclastogenesis assays. This correlated with fewer multinucleated osteoclast-like cells and more trabecular bone volume and number in 26-wk-old male IL-23p19(-/-) mice compared with control animals. Collectively, our data suggest that systemic IL-23 exposure induces the expansion of a myeloid lineage osteoclast precursor, and targeting IL-23 pathway may combat inflammation-driven bone destruction as observed in rheumatoid arthritis and other autoimmune arthritides.


Effects of polarity on the structures and charge states of native-like proteins and protein complexes in the gas phase.
Native mass spectrometry and ion mobility spectrometry were used to investigate the gas-phase structures of selected cations and anions of proteins and protein complexes with masses ranging from 6 to 468 kDa. Under the same solution conditions, the average charge states observed for all native-like anions were less than those for the corresponding cations. Using an rf-confining drift cell, similar collision cross sections were measured in positive and negative ion mode suggesting that anions and cations have very similar structures. This result suggests that for protein and protein complex ions within this mass range, there is no inherent benefit to selecting a specific polarity for capturing a more native-like structure. For peptides and low-mass proteins, polarity and charge-state dependent structural changes may be more significant. The charged-residue model is most often used to explain the ionization of large macromolecules based on the Rayleigh limit, which defines the upper limit of charge that a droplet can hold. Because ions of both polarities have similar structures and the Rayleigh limit does not depend on polarity, these results cannot be explained by the charged-residue model alone. Rather, the observed charge-state distributions are most consistent with charge-carrier emissions during the final stages of analyte desolvation, with lower charge-carrier emission energies for anions than the corresponding cations. These results suggest that the observed charge-state distributions in most native mass spectrometry experiments are determined by charge-carrier emission processes; although the Rayleigh limit may determine the gas-phase charge states of larger species, e.g., virus capsids.


Identification of Equine Lactadherin-derived Peptides That Inhibit Rotavirus Infection via Integrin Receptor Competition.
Human rotavirus is the leading cause of severe gastroenteritis in infants and children under the age of 5 years in both developed and developing countries. Human lactadherin, a milk fat globule membrane glycoprotein, inhibits human rotavirus infection in vitro, whereas bovine lactadherin is not active. Moreover, it protects breastfed infants against symptomatic rotavirus infections. To explore the potential antiviral activity of lactadherin sourced by equines, we undertook a proteomic analysis of milk fat globule membrane proteins from donkey milk and elucidated its amino acid sequence. Alignment of the human, bovine, and donkey lactadherin sequences revealed the presence of an Asp-Gly-Glu (DGE) α2β1 integrin-binding motif in the N-terminal domain of donkey sequence only. Because integrin α2β1 plays a critical role during early steps of rotavirus host cell adhesion, we tested a minilibrary of donkey lactadherin-derived peptides containing DGE sequence for anti-rotavirus activity. A 20-amino acid peptide containing both DGE and RGD motifs (named pDGE-RGD) showed the greatest activity, and its mechanism of antiviral action was characterized; pDGE-RGD binds to integrin α2β1 by means of the DGE motif and inhibits rotavirus attachment to the cell surface. These findings suggest the potential anti-rotavirus activity of equine lactadherin and support the feasibility of developing an anti-rotavirus peptide that acts by hindering virus-receptor binding.


BUB1 and CENP-U, Primed by CDK1, Are the Main PLK1 Kinetochore Receptors in Mitosis.
Reflecting its pleiotropic functions, Polo-like kinase 1 (PLK1) localizes to various sub-cellular structures during mitosis. At kinetochores, PLK1 contributes to microtubule attachments and mitotic checkpoint signaling. Previous studies identified a wealth of potential PLK1 receptors at kinetochores, as well as requirements for various mitotic kinases, including BUB1, Aurora B, and PLK1 itself. Here, we combine ectopic localization, in vitro reconstitution, and kinetochore localization studies to demonstrate that most and likely all of the PLK1 is recruited through BUB1 in the outer kinetochore and centromeric protein U (CENP-U) in the inner kinetochore. BUB1 and CENP-U share a constellation of sequence motifs consisting of a putative PP2A-docking motif and two neighboring PLK1-docking sites, which, contingent on priming phosphorylation by cyclin-dependent kinase 1 and PLK1 itself, bind PLK1 and promote its dimerization. Our results rationalize previous observations and describe a unifying mechanism for recruitment of PLK1 to human kinetochores.


A new catheter design using needle electrode for subendocardial RF ablation of ventricular muscles: finite element analysis and in vitro experiments.
Radio-frequency (RF) cardiac ablation has been very successful for treating arrhythmias related with atrioventricular junction and accessory pathways with successful cure rates of more than 90%. Even though ventricular tachycardia (VT) is a more serious problem, it is known to be rather difficult to cure VT using RF ablation. In order to apply RF ablation to VT, we usually need to create a deeper and wider lesion. Conventional RF ablation electrodes often fail to produce such a lesion. We propose a catheter-electrode design including one or more needle electrodes with a diameter of 0.5-1.0 mm and length of 2.0-10 mm to create a lesion large enough to treat VT. One temperature sensor could be placed at the middle of the needle electrode for temperature-controlled RF ablation. From finite element analyses and in vitro experiments, we found that the depth of a lesion is 1-2 mm deeper than the insertion depth of the needle and the width increases as we increase the diameter of the needle and the time duration. We showed that a single needle electrode can produce a lesion with about 10-mm width and any required depth. If a wider lesion is required, more than one needle with suggested structures can be used. Or, repeated RF ablations around a certain area using one needle could produce a cluster of lesions. In some cases, a catheter with both conventional electrode and needle electrode at its tip may be beneficial to take advantage of both types of electrode.


Relationship between repetitive work and the prevalence of carpal tunnel syndrome in part-time and full-time female supermarket cashiers: a quasi-experimental study.
To investigate the prevalence of Carpal Tunnel Syndrome (CTS) in full-time and part-time supermarket cashiers exposed to a different weekly duration of biomechanical load. All the 269 cashiers and 127 office workers were asked to participate. The protocol included ergonomic risk assessment, collection of personal and clinical data and bilateral electrodiagnostic study of the median nerve. CTS symptoms were defined as past and/or current nocturnal and/or diurnal numbness, tingling, burning or pain involving at least one of the first three fingers. Results were evaluated according to two case definitions based on current symptoms and on the combination of current symptoms and slowing of sensory conduction velocity from wrist to palm, respectively. Difference in proportions of CTS symptoms and cases was evaluated by the Pearson's chi-square (chi(2)) test, univariate and multivariate logistic regression analyses were performed to determine the impact of weekly exposure. The final female study population included 71 full-time cashiers, 155 part-time cashiers and 98 office workers. Ergonomic risk level was rated 5 for hand activity level and 4 for peak of force according to ACGIH. The intersection of the two values fell on the threshold limit value line, confirming the possible exposure to biomechanical risk factors for CTS. The prevalence of current CTS symptoms was higher among full-time (31.0%) than in part-time cashiers (19.3%) or controls (16.3%) (p = 0.055). A similar pattern was found for CTS past symptoms and cases. Univariate analysis showed that full-time cashiers had a 2.3 fold increased risk for CTS specific current symptoms than control subjects. A similar trend also emerged for CTS cases but was not significant (Odds ratios 1.23). Multivariate logistic regression analysis confirmed the increased risk for CTS current symptoms in full-time cashiers. Intensive manual work associated with inadequate recovery time might have generated an impairment of the median nerve at the wrist level proportionally increasing with duration of hand use. Our study can provide useful information both for ergonomic risk assessment and work organization.


Liposomal drug delivery: a versatile platform for challenging clinical applications.
Liposomes are lipid based vesicular systems that offer novel platform for versatile drug delivery to target cell. Liposomes were first reported by Bangham and his co-workers in 1964 (1). Since then, liposomes have undergone extensive research with the prime aim to optimize encapsulation, stability, circulation time and target specific drug delivery. Manipulation of a liposome's lipid bilayer and surface decoration with selective ligands has transformed conventional liposomes into adaptable and multifunctional liposomes. Development of liposomes with target specificity provide the prospect of safe and effective therapy for challenging clinical applications. Bioresponsive liposomes offer the opportunity to release payload in response to tissue specific microenvironment. Incorporation of novel natural and synthetic materials has extended their application from stable formulations to controlled release targeted drug delivery systems. Integration and optimization of multiple features into one system revolutionized research in the field of cancer, gene therapy, immunotherapy and infectious diseases. After 50 years since the first publication, this review is aimed to highlight next generation of liposomes, their preparation methods and progress in clinical applications.


Kinetics of amyloplast sedimentation in gravistimulated maize coleoptiles.
Inner mesophyll cells from coleoptiles of Zea mays L. cv. Merit were fixed after varying periods of gravistimulation. A statistically significant amount (17-21%) of amyloplast sedimentation occurred in these cells after 30 s of gravistimulation. The presentation time is approx. 40 s or less. The accumulation of amyloplasts near the new lower wall shows a linear relationship to the logarithm of the gravistimulation time (r=0.92 or higher). The intercept of this line with the baseline value of amyloplasts in vertical coleoptiles indicates that the number of amyloplasts on the new lower wall begins increasing 11-15 s after the onset of gravistimulation. Direct observations of living cells confirm that many amyloplasts sediment within less than 15-30 s. These rapid kinetics are consistent with the classical statolith hypothesis of graviperception involving the sedimentation of amyloplasts to the vicinity of the new lower wall.


Application of evidence on probiotics, prebiotics and synbiotics by food industry: a descriptive study.
This study assessed how the food industry applies the knowledge and evidence gained from synbiotics, probiotics or prebiotics research in infants, on the general paediatric population. This study also explored: what happens after the clinical trials using infant formula are completed, data is published or remains unpublished; the effectiveness and type of medium the formula manufacturers use to educate consumers on probiotic, prebiotic or synbiotic infant formula. This was a descriptive study (a survey) that used a structured questionnaire. All listed companies that manufacture and / or market food products with added probiotics, prebiotics or synbiotics for infants were identified and invited to participate. People responsible for research and development were invited to participate in the survey. A letter of invitation was sent to selected participants and if they expressed willingness to take part in the study, a questionnaire with a written consent form was sent. Descriptive statistics and associations between categorical variables were to be tested using a Chi-square test, a p < 0.05 was statistically significant.A total of 25 major infant formulas, baby food manufacturers were identified, invited to participate in the survey. No company was willing to participate in the survey for different reasons: failure to take any action 5 (20%), decision to participate indefinitely delayed 2 (8%), sensitivity of requested information 3 (12%), company does not conduct clinical trials 1 (4%), company declined without further information 4 (16%), erroneous contact information 6 (24%), refusal by receptionists to forward telephone calls to appropriate staff 3 (12%), language barrier 3 (12%), company no longer agrees to market research 1 (4%). Due to a poor response rate in this study, no conclusion could be drawn on how the food industry applies evidence gained through probiotics, prebiotics or synbiotics research on infants for the benefit of the general paediatric population. More information and greater transparency is needed from the infant formula manufacturers on how they apply the evidence gained from the research on probiotics, prebiotics and synbiotics on infants.


Genetic analysis of the bipolar pattern of bud site selection in the yeast Saccharomyces cerevisiae.
Previous analysis of the bipolar budding pattern of Saccharomyces cerevisiae has suggested that it depends on persistent positional signals that mark the region of the division site and the tip of the distal pole on a newborn daughter cell, as well as each previous division site on a mother cell. In an attempt to identify genes encoding components of these signals or proteins involved in positioning or responding to them, we identified 11 mutants with defects in bipolar but not in axial budding. Five mutants displaying a bipolar budding-specific randomization of budding pattern had mutations in four previously known genes (BUD2, BUD5, SPA2, and BNI1) and one novel gene (BUD6), respectively. As Bud2p and Bud5p are known to be required for both the axial and bipolar budding patterns, the alleles identified here probably encode proteins that have lost their ability to interact with the bipolar positional signals but have retained their ability to interact with the distinct positional signal used in axial budding. The function of Spa2p is not known, but previous work has shown that its intracellular localization is similar to that postulated for the bipolar positional signals. BNI1 was originally identified on the basis of genetic interaction with CDC12, which encodes one of the neck-filament-associated septin proteins, suggesting that these proteins may be involved in positioning the bipolar signals. One mutant with a heterogeneous budding pattern defines a second novel gene (BUD7). Two mutants budding almost exclusively from the proximal pole carry mutations in a fourth novel gene (BUD9). A bud8 bud9 double mutant also buds almost exclusively from the proximal pole, suggesting that Bud9p is involved in positioning the proximal pole signal rather than being itself a component of this signal.


Hypodontia prevalence and pattern in women with epithelial ovarian cancer.
To analyze the possible association between hypodontia and epithelial ovarian cancer (EOC), with the special interest in hypodontia pattern. One hundred twenty women with EOC treated at the Department of Gynecologic and Breast Oncology at the University Clinical Centre and 120 gynecologically healthy women of the same average age were reviewed for the presence and pattern of hypodontia. Collected data were analyzed for frequency, tooth type, location per jaw and side, number of missing teeth per person, and family history of hypodontia. The results of the study showed prevalence of hypodontia in 19.2% of women with EOC and in 6.7% of women in the control group (P = .004). The most frequently missing teeth for women with EOC and women in the control group were maxillary second premolars and maxillary lateral incisors, respectively. Unilateral occurrence of hypodontia was more common than bilateral occurrence in women with EOC (P = .034). Of women with EOC and hypodontia, 21.7% reported a positive family history of hypodontia compared with no report in the control group of women with hypodontia (P = .150). The results statistically support possible association between EOC and hypodontia. Because hypdontia can be recognized early in life, this finding could possibly help in earlier detection of EOC, resulting in better prognosis and treatment in earlier stages of the disease. Earlier EOC diagnosis and treatment could save many lives.


Regulation of Ras signaling specificity by protein kinase C.
Ras proteins have the capacity to bind to and activate at least three families of downstream target proteins: Raf kinases, phosphatidylinositol 3 (PI 3)-kinase, and Ral-specific guanine nucleotide exchange factors (Ral-GEFs). We have previously shown that the Ras/Ral-GEF and Ras/Raf pathways oppose each other upon nerve growth factor stimulation, with the former promoting proliferation and the latter promoting cell cycle arrest. Moreover, the pathways are not activated equally. While the Ras/Raf/Erk signaling pathway is induced for hours, the Ras/Ral-GEF/Ral signaling pathway is induced for only minutes. Here we show that this preferential down-regulation of Ral signaling is mediated, at least in part, by protein kinase C (PKC). In particular, we show that PKC activation by phorbol ester treatment of cells blocks growth factor-induced Ral activation while it enhances Erk activation. Moreover, suppression of growth factor-induced PKC activation enhances and prolongs Ral activation. PKC does not influence the basal activity of the Ral-GEF designated Ral-GDS but suppresses its activation by Ras. Interestingly, Ras binding to the C-terminal Ras binding domain of Ral-GDS is not affected by PKC activity. Instead, suppression of Ral-GDS activation occurs through the region N terminal to the catalytic domain, which becomes phosphorylated in response to phorbol ester treatment of cells. These findings identify a role for PKC in determining the specificity of Ras signaling by its ability to differentially modulate Ras effector protein activation.


Rapid inventory of the ant assemblage in a temperate hardwood forest: species composition and assessment of sampling methods.
Ants are key indicators of ecological change, but few studies have investigated how ant assemblages respond to dramatic changes in vegetation structure in temperate forests. Pests and pathogens are causing widespread loss of dominant canopy tree species; ant species composition and abundance may be very sensitive to such losses. Before the experimental removal of red oak trees to simulate effects of sudden oak death and examine the long-term impact of oak loss at the Black Rock Forest (Cornwall, NY), we carried out a rapid assessment of the ant assemblage in a 10-ha experimental area. We also determined the efficacy in a northern temperate forest of five different collecting methods--pitfall traps, litter samples, tuna fish and cookie baits, and hand collection--routinely used to sample ants in tropical systems. A total of 33 species in 14 genera were collected and identified; the myrmecines, Aphaenogaster rudis and Myrmica punctiventris, and the formicine Formica neogagates were the most common and abundant species encountered. Ninety-four percent (31 of 33) of the species were collected by litter sampling and structured hand sampling together, and we conclude that, in combination, these two methods are sufficient to assess species richness and composition of ant assemblages in northern temperate forests. Using new, unbiased estimators, we project that 38-58 ant species are likely to occur at Black Rock Forest. Loss of oak from these forests may favor Camponotus species that nest in decomposing wood and open habitat specialists in the genus Lasius.


Clinical Complexity and Use of Antipsychotics and Restraints in Long-Term Care Residents with Parkinson's Disease.
Patients with Parkinson's disease (PD) and/or Parkinsonism are affected by a complex burden of comorbidity. Many ultimately require institutional care, where they may be subject to the application of physical restraints or the prescription of antipsychotic medications, making them more vulnerable to adverse outcomes. The objectives of this paper are to: 1) describe the clinical complexity of older institutionalized persons with PD; and 2) examine patterns and predictors of restraint use and prescription of antipsychotics in this population. Population-based cross-sectional cohort study. Residents with PD and/or Parkinsonism living in long-term care (LTC) facilities in 6 Canadian provinces and 1 Northern Territory and Complex Continuing Care (CCC) facilities in Manitoba and Ontario, Canada. The RAI MDS 2.0 instrument was used to assess all LTC residents and CCC residents. Clinical characteristics and the prevalence of major comorbidities were examined. Multivariate modeling was used to identify the characteristics of PD residents most associated with the prescription of antipsychotics and the use of restraints in LTC and CCC facilities. Residents with PD in LTC and CCC exhibit a high prevalence of dementia, major psychiatric disorders, stroke, heart failure, chronic obstructive pulmonary disease and diabetes mellitus. More than 90% of LTC and CCC residents with PD had cognitive impairment; with more than half having moderate to severe impairment. Residents with PD were more likely to receive antipsychotics than those without PD. Antipsychotic use was associated with psychosis and aggressive behaviours, but also with unsteady gait and higher comorbidity and medication count. Similarly, although more common in CCC than LTC facilities, both psychosis and aggressive behaviours were associated with restraint use, as was greater cognitive and functional impairment, and urinary incontinence. Younger age, male gender, and lower physician access were all associated with greater antipsychotic and restraint use. LTC and CCC residents with PD are very complex medically. Use of antipsychotics and restraints is common, and their use is often associated with factors other than psychosis or aggression.


A conceptual framework to facilitate the mental health of student nurses working with persons with intellectual disabilities.
Student nurses (SNs) experience emotional discomfort during placement in the clinical psychiatric learning environment. This may negatively influence their mental health. Limited support is available to assist both SNs working with persons with intellectual disabilities and nurse educators during clinical accompaniment. This article aims to discuss the generation of this framework to enhance student support. A theory-generative, qualitative, exploratory, descriptive, contextual design was utilised to develop the framework by applying four steps. In step 1 concept analysis identified the central concept through field work. Data were collected from 13 SNs purposively selected from a specific higher educational institution in Gauteng through two focus group interviews, reflective journals, a reflective letter, naïve sketches, drawings and field notes and analysed with thematic coding. The central concept was identified from the results, supported by a literature review and defined by essential attributes. The central concept was classified through a survey list and demonstrated in a model case. In step 2 the central concepts were placed into relationships with each other. The conceptual framework was described and evaluated in step 3 and guidelines for implementation were described in step 4. The focus of this article will be on generating the conceptual framework. The central concept was 'the facilitation of engagement on a deeper emotional level of SNs'. The conceptual framework was described and evaluated. The conceptual framework can enhance the educational practices of nurse educators and can SN's practices of care for persons with intellectual disabilities.


Amyotrophic lateral sclerosis (motor neuron disease): proposed mechanisms and pathways to treatment.
Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disorder characterised by loss of motor neurons. The cause of disease is unknown other than in the rare cases of familial disease arising from mutations in the superoxide dismutase 1 gene. Many theories for pathogenesis have been proposed - including oxidative stress, excitotoxicity, mitochondrial dysfunction and abnormal protein aggregation - based on studies of human post mortem tissue, research on animal models, and in vitro work. Here we review the evidence for the main pathogenic mechanisms and outline how they might interact to cause motor neuron death. Clinical trials have as yet failed to identify any truly effective therapies in ALS, with only riluzole providing a modest improvement in survival. Ongoing trials are exploring the value of antiglutamatergic agents, including the cephalosporin antibiotic ceftriaxone, as well as antioxidants, mitochondrial enhancers and anti-apoptotic drugs. It is likely that effective therapy will involve combinations of agents acting on different mechanisms. Gene therapy with neurotrophic factors will soon be in clinical trials, while work on stem cell therapy remains preclinical. In addition to finding effective therapies, research also needs to identify early disease markers because therapy is likely to be of most benefit when given early in the course of disease.


Association between socioeconomic deprivation and surgical complications in adults undergoing ankle fracture fixation: a population-based analysis
Few studies have investigated the outcomes of surgical fracture care among socially deprived patients despite the increased incidence of fractures and the inequality of care received in this group. We evaluated whether socioeconomic deprivation affected the complications and subsequent management of marginalized/homeless patients following surgery for ankle fracture. In this retrospective, population-based cohort study involving 202 hospitals in Ontario, Canada, we evaluated 45 444 patients who underwent open reduction and internal fixation (ORIF) for ankle fracture performed by 710 different surgeons between Jan. 1, 1994, and Dec. 31, 2011. Multivariable logistic regression models were used to assess the association between deprivation and shorter-term outcomes within 1 year (implant removal, repeat ORIF, irrigation and débridement owing to infection, and amputation). Multivariable Cox proportional hazards models were used to assess longer-term outcomes up to 20 years (ankle fusion and ankle arthroplasty). A higher level of deprivation was associated with an increased risk of irrigation and débridement (quintile 5 v. quintile 1: odds ratio [OR] 2.14, 95% confidence interval [CI] 1.25–3.67, p = 0.0054) and amputation (quintile 4 v. quintile 1: OR 3.56, 95% CI 1.01–12.4, p = 0.0466). It was more common for less deprived patients to have their hardware removed (quintile 5 v. quintile 1: OR 0.822, 95% CI 0.76–0.888, p < 0.0001). There was no correlation between marginalization and subsequent revision ORIF, ankle fusion, or ankle arthroplasty. Marginalized patients are at a significantly increased risk of infection and amputation following surgical treatment of ankle fractures. However, these complications are still extremely uncommon among this group. Socioeconomic deprivation should not prohibit marginalized patients from receiving surgery for unstable ankle fractures.


A prophylactic multi-strain probiotic treatment to reduce the absorption of toxic elements: In-vitro study and biomonitoring of breast milk and infant stools.
Potential exposure to toxic elements initially occurs during gestation and after birth via breast milk, which is the principal source of nutrients for infants during the first months of life. In this study, we evaluated whether maternal oral supplementation with a multi-strain probiotic product can protect infants from exposure to arsenic (As), cadmium (Cd), mercury (Hg), and lead (Pb) via breast milk. In-vitro studies of the bacterial strains present in this probiotic product showed a high bacterial tolerance for As, Cd, Hg, and Pb, and good binding capacity for Cd, Hg, and Pb (72%, 81%, and 64%, respectively) within 1 h of contact. We evaluated concentrations (5 mg L-1 for Cd and Pb, and 2 mg L-1 for Hg) that largely exceeded the provisional tolerable weekly intake of these toxic elements via food or water applicable for human consumption. Changes in the levels of these elements in breast milk and newborn stools were evaluated in the control (orally supplemented with placebo) and experimental (orally supplemented with probiotic) groups at birth (t0), 15 days (t15), and 30 days (t30) after delivery. Elemental analysis of breast milk did not show significant differences between the control and experimental groups at different stages of lactation; however, stool samples obtained from newborns of mothers supplemented with the probiotic product showed that Cd levels were significantly reduced (by 26%) at t15 compared with the levels of the controls. Our data did not show an association between concentration of toxic elements in breast milk and that in newborn stools. Indeed, the concentration of Cd, Hg, and Pb in breast milk decreased during the lactation period, whereas the levels of these elements in newborn stools were stable over time. Although our in-vitro data indicate that the consortium of these probiotic strains can absorb toxic compounds, this study was limited by its small sample size and potential uncontrolled confounding effects, such as maternal diet and lifestyle. Therefore, we could not confirm whether prophylactic use of this probiotic product can reduce the absorption of toxic elements. The risk assessment in the studied population evidenced a margin of exposure (MOE) of 1, or between 1 and 10 for Pb, and lower than 50 for As. This poses a potential risk for breastfed infants, indicating that interventions aimed to avoid breastfeeding-related health risks remain a major challenge in public health.


Negative epidemiological association between HSV-1 and HSV-2 infections.
Existing evidence on an epidemiological association between herpes simplex virus (HSV) type 1 and type 2 infections remains conflicting and inconclusive. Using a multi-national database of HSV-1/2 serological testing, we aimed to assess the existence of an association between both infections. An HSV-1/2 cross-sectional serological testing database was assembled by merging databases of seroprevalence studies on men blood donors residing currently in Qatar, but from different countries. Specimens were tested for anti-HSV-1 IgG antibodies using HerpeSelect® 1 ELISA, and for anti-HSV-2 IgG antibodies following a two-test algorithm: HerpeSelect® 2 ELISA to test the sera, and Euroline-WB to confirm positive and equivocal specimens. Logistic regressions were conducted to estimate unadjusted and adjusted infection odds ratios. Serological testing for HSV-1/2 was performed on 2522 specimens. Sero-positivity for HSV-1 and HSV-2 was identified in 2053 (81.5%) and 87 (3.5%) specimens, respectively. Univariable analyses estimated higher odds of HSV-2 infection with increasing age and increasing country income level, and an unadjusted odds ratio with HSV-1 sero-positivity of 0.71 (95% CI 0.43-1.17; p-value 0.172). Adjusting for age and country income level, the adjusted odds ratio of HSV-2 infection with HSV-1 sero-positivity was 0.51 (95% CI 0.30-0.87; p-value 0.013). Sensitivity analyses confirmed this association. There is a negative association between HSV-1 and HSV-2 infections, suggestive of a protective effect for HSV-1 sero-positivity against HSV-2 acquisition. This finding supports earlier pooled but inconclusive evidence from prospective studies, yet contrasts with pooled findings of earlier cross-sectional studies.


Biliary cysts in children--long-term follow-up in Taiwan.
This study analyzed the clinical presentation, postoperative morbidity and mortality and incidence of associated extrahepatic biliary atresia in children with biliary cysts in Taiwan. We retrospectively reviewed the records of 158 pediatric patients with biliary cysts seen between June 1981 and July 2004, with follow-up ranging from 12 months to 22 years (mean, 11.2 +/- 6.1 years). Patients were divided into three groups: biliary atresia-associated biliary cyst (BABC, 21 patients), non-biliary atresia-associated choledochal cyst (NBACC) in infancy (37 patients), and late NBACC (> 1 year of age, 100 patients). BABC accounted for 36.2% of the infantile biliary cysts in this study. Extrahepatic cysts in late NBACC had a greater mean diameter than those in infantile NBACC and BABC (21.5 mm vs. 16.0 mm vs. 7.9 mm, p < 0.001). Cholangitis was the most serious complication within 3 months postoperatively in all three groups, resulting in four deaths (two in the infantile NBACC group and one each in the other two groups). Liver cirrhosis developed during long-term follow-up in nine of the 21 patients with BABC, four of whom died. Three of these nine patients underwent liver transplantation and remained well during follow-up. Chronic complications in NBACC occurred mainly in late IVa cases, with persistent intrahepatic dilatation developing in 12 of 35 patients and intrahepatic stones in five. Elevation of serum alanine aminotransferase (ALT) was found preoperatively in 85% of late NBACC and 35% of infantile NBACC cases. Postoperative normalization of ALT occurred after a mean of 152 +/- 23 days and 158 +/- 67 days in late NBACC and infantile NBACC, respectively. Higher ALT levels before operation were associated with a longer period until normalization. The possibility of BABC must be included in the differential diagnosis when a small extrahepatic cyst (< 8 mm in diameter) with prolonged jaundice is found in infancy. Postoperative follow-up is essential for patients with NBACC due to their frequently prolonged elevation of serum ALT and possibility of residual intrahepatic dilatation. Cholangitis was the major cause of death within 3 months postoperatively in this study.


Pharmacological interventions for non-ulcer dyspepsia.
The commonest cause of upper gastrointestinal symptoms is non-ulcer dyspepsia (NUD) and yet the pathophysiology of this condition has been poorly characterised and the optimum treatment is uncertain. It is estimated that pound 450 million is spent on dyspepsia drugs in the UK each year. This review aims to determine the effectiveness of six classes of drugs (antacids, histamine H2 antagonists, proton pump inhibitors, prokinetics, mucosal protecting agents and antimuscarinics) in the improvement of either the individual or global dyspepsia symptom scores and also quality of life scores patients with non-ulcer dyspepsia. Trials were located through electronic searches of the Cochrane Controlled Trials Register (CCTR), MEDLINE, EMBASE, CINAHL and SIGLE, using appropriate subject headings and text words, searching bibliographies of retrieved articles, and through contacts with experts in the fields of dyspepsia and pharmaceutical companies. All randomised controlled trials (RCTs) comparing drugs of any of the six groups with each other or with placebo for non-ulcer dyspepsia (NUD). Data were collected on dyspeptic symptom scores either individual or global symptom assessments and also quality of life scores and adverse effects. A total of 11796 citations were obtained. 155 trials were retrieved and 96 trials fulfilled our eligibility criteria. However, subsequent data extraction was not possible in 31 trials. The final 65 trials were included in the meta-analysis. Prokinetics (14 trials with dichotomous outcomes generating 1053 patients; relative risk reduction [RRR] = 48%; 95% confidence intervals [CI] = 27% to 63%), H2RAs (11 trials generating 2,164 patients; RRR = 22%; 95% CI = 7% to 35%) and PPIs (7 trials generating 3,031 patients; RRR = 14%; 95% CI = 5% to 23%) were significantly more effective than placebo. Bismuth salts (6 trials generating 311 patients; RRR = 40%; 95% CI = -3 to 65%) were superior to placebo but this was of marginal statistical significance. Antacids (one trial generating 109 patients; RRR = -2%; 95% CI = -36% to 24%) and sucralfate (two trials generating 246 patients; RRR = 29%; 95% CI = -40% to 64%) were not statistically significantly superior to placebo. A funnel plot suggested that the prokinetic and H2RA results could be due to publication bias. There is evidence that anti-secretory therapy may be effective in NUD. The trials evaluating prokinetic therapy are difficult to interpret as the meta-analysis result could have been due to publication bias. The effect of these drugs is likely to be small and many patients will need to take them on a long-term basis so economic analyses would be helpful and ideally the therapies assessed need to be inexpensive and well tolerated.


Host specificity in the Richelia-diatom symbiosis revealed by hetR gene sequence analysis.
The filamentous heterocyst-forming cyanobacterium Richelia intracellularis forms associations with diatoms and is very abundant in tropical and subtropical seas. The genus Richelia contains only one species, R. intracellularis Schmidt, although it forms associations with several diatom genera and has considerable variation in size and morphology. The genetic diversity, and possible host specificity, within the genus Richelia is unknown. Using primers against hetR, a gene unique for filamentous cyanobacteria, specific polymerase chain reaction (PCR) products were obtained from natural populations of R. intracellularis filaments associated with three diatom genera. Phylogenetic analyses of these sequences showed that they were all in the same clade. This clade contained only the R. intracellularis sequences. The genetic affiliation of hetR sequences of R. intracellularis to those of other heterocystous cyanobacteria strongly suggests that it was not closely related to endosymbiotic Nostoc spp. hetR sequences. Sequences from R. intracellularis-Hemiaulus membranaceus sampled in the Atlantic and Pacific Oceans were almost identical, demonstrating that the genetic relatedness was not dependent on geographical location. All sequences displayed a deep divergence between symbionts from different genera and a high degree of host specificity.


Evolution of eukaryotic single-stranded DNA viruses of the Bidnaviridae family from genes of four other groups of widely different viruses.
Single-stranded (ss)DNA viruses are extremely widespread, infect diverse hosts from all three domains of life and include important pathogens. Most ssDNA viruses possess small genomes that replicate by the rolling-circle-like mechanism initiated by a distinct virus-encoded endonuclease. However, viruses of the family Bidnaviridae, instead of the endonuclease, encode a protein-primed type B DNA polymerase (PolB) and hence break this pattern. We investigated the provenance of all bidnavirus genes and uncover an unexpected turbulent evolutionary history of these unique viruses. Our analysis strongly suggests that bidnaviruses evolved from a parvovirus ancestor from which they inherit a jelly-roll capsid protein and a superfamily 3 helicase. The radiation of bidnaviruses from parvoviruses was probably triggered by integration of the ancestral parvovirus genome into a large virus-derived DNA transposon of the Polinton (polintovirus) family resulting in the acquisition of the polintovirus PolB gene along with terminal inverted repeats. Bidnavirus genes for a receptor-binding protein and a potential novel antiviral defense modulator are derived from dsRNA viruses (Reoviridae) and dsDNA viruses (Baculoviridae), respectively. The unusual evolutionary history of bidnaviruses emphasizes the key role of horizontal gene transfer, sometimes between viruses with completely different genomes but occupying the same niche, in the emergence of new viral types.


Risk analysis reveals global hotspots for marine debris ingestion by sea turtles.
Plastic marine debris pollution is rapidly becoming one of the critical environmental concerns facing wildlife in the 21st century. Here we present a risk analysis for plastic ingestion by sea turtles on a global scale. We combined global marine plastic distributions based on ocean drifter data with sea turtle habitat maps to predict exposure levels to plastic pollution. Empirical data from necropsies of deceased animals were then utilised to assess the consequence of exposure to plastics. We modelled the risk (probability of debris ingestion) by incorporating exposure to debris and consequence of exposure, and included life history stage, species of sea turtle and date of stranding observation as possible additional explanatory factors. Life history stage is the best predictor of debris ingestion, but the best-fit model also incorporates encounter rates within a limited distance from stranding location, marine debris predictions specific to the date of the stranding study and turtle species. There is no difference in ingestion rates between stranded turtles vs. those caught as bycatch from fishing activity, suggesting that stranded animals are not a biased representation of debris ingestion rates in the background population. Oceanic life-stage sea turtles are at the highest risk of debris ingestion, and olive ridley turtles are the most at-risk species. The regions of highest risk to global sea turtle populations are off of the east coasts of the USA, Australia and South Africa; the east Indian Ocean, and Southeast Asia. Model results can be used to predict the number of sea turtles globally at risk of debris ingestion. Based on currently available data, initial calculations indicate that up to 52% of sea turtles may have ingested debris.


The effect of carbohydrate mouth rinse on 1-h cycle time trial performance.
To investigate the possible role of carbohydrate (CHO) receptors in the mouth in influencing exercise performance, seven male and two female endurance cyclists (VO(2max) 63.2 +/- 2.7 (mean +/- SE) mL.kg*(-1).min(-1)) completed two performance trials in which they had to accomplish a set amount of work as quickly as possible (914 +/- 40 kJ). On one occasion a 6.4% maltodextrin solution (CHO) was rinsed around the mouth for every 12.5% of the trial completed. On the other occasion, water (PLA) was rinsed. Subjects were not allowed to swallow either the CHO solution or water, and each mouthful was spat out after a 5-s rinse. Performance time was significantly improved with CHO compared with PLA (59.57 +/- 1.50 min vs 61.37 +/- 1.56 min, respectively, P = 0.011). This improvement resulted in a significantly higher average power output during the CHO compared with the PLA trial (259 +/- 16 W and 252 +/- 16 W, respectively, P = 0.003). There were no differences in heart rate or rating of perceived exertion (RPE) between the two trials (P > 0.05). The results demonstrate that carbohydrate mouth rinse has a positive effect on 1-h time trial performance. The mechanism responsible for the improvement in high-intensity exercise performance with exogenous carbohydrate appears to involve an increase in central drive or motivation rather than having any metabolic cause. The nature and role of putative CHO receptors in the mouth warrants further investigation.


End points for colon cancer adjuvant trials: observations and recommendations based on individual patient data from 20,898 patients enrolled onto 18 randomized trials from the ACCENT Group.
The traditional end point for colon adjuvant clinical trials is overall survival (OS). We previously validated disease-free survival (DFS) after 3-year follow-up as an excellent predictor of 5-year OS results. Here we explore shorter term DFS and OS end points, as well as stage dependency. Individual patient data from 18 phase III trials including 43 arms and 20,898 patients were pooled. Association measures included correlation of event rates within arms, correlation of hazard ratios (HRs) between arms, trial level significance comparisons (via log-rank testing), and a formal surrogacy model. DFS at earlier times was less accurate in predicting OS than 3-year DFS, but 2-year DFS remained a strong predictor. DFS with 1-year minimum follow-up demonstrated perfect negative predicted value; all trials negative at 1 year for DFS were negative for 5-year OS. OS with 3-year minimum follow-up was also an excellent predictor for 5-year OS; OS at earlier time points provided inaccurate prediction. The association between 3-year DFS and 5-year OS was greater for stage III patients; correlation of HR within trials was 0.92 (95% CI, 0.85 to 0.95) for stage III patients and 0.70 (95% CI, 0.44 to 0.80) for stage II patients. DFS outcomes after 2- or 3-year median follow-up are excellent predictors of 5-year OS. DFS outcomes are appropriate for trials in which the majority of patients are stage III. DFS after 2- or 3-year median follow-up should be considered as the primary end point in future colon adjuvant trials.


Growth and targeting of subplate axons and establishment of major cortical pathways.
In the developing mammalian neocortex, the first postmitotic neurons form the "preplate" superficial to the neuroepithelium. The preplate is later split into a marginal zone (layer 1) and subplate by cortical plate neurons that form layers 2-6. Cortical efferent axons from layers 5 and 6 and cortical afferent axons from thalamus pass between cortex and subcortical structures through the internal capsule. Here, we identify in rats the axonal populations that establish the internal capsule, and characterize the potential role of subplate axons in the development of cortical efferent and afferent projections. The early growth of cortical efferent and afferent axons was studied using 1-1'-dioctodecyl-3,3,3',3'-tetramethylindocarbocyanine perchlorate (Dil) as an anterograde and retrograde tracer in aldehyde-fixed brains of embryonic rats. Cortical axons first enter the nascent internal capsule on embryonic day (E) 14 and originate from lateral and anterior cortex; axons from posterior cortex extend rostrally but do not yet exit cortex. The labeled axons, tipped by growth cones with complex morphologies, take a pathway deep to the preplate. Preplate neurons extend these early cortical efferents, based on the developmental stage of the cortex, and on their location and morphology. Most of these cells later occupy the subplate. Cortical plate neurons extend axons into the internal capsule by E16. En route to the internal capsule, cortical plate axons take the same path as the earlier-growing preplate axons, through the intermediate zone deep to subplate. Subplate axons reach thalamus by E16; the first cortical plate axons enter thalamus about a day later. Thalamic axons enter cortex by E16, prior to other cortical afferents. On E15, both preplate and thalamic axons reach the midpoint of the internal capsule. To determine the subcortical distribution of subplate axons, we used Dil as a retrograde tracer in aldehyde-fixed brains and fast blue and rhodamine-B-isothiocyanate as in vivo retrograde markers in neonatal rats. Tracers were injected into the superior colliculus, the principal midbrain target of layer 5 neurons, at times before, during, and after the arrival of cortical axons, or into the subcortical pathway of primary layer 5 axons at two points, the cerebral peduncle caudal to the internal capsule, and the pyramidal decussation at the junction of the hindbrain and spinal cord, at times shortly after the passing of cortical axons. In every case, the labeled neurons are confined to layer 5; subplate neurons are not labeled.(ABSTRACT TRUNCATED AT 400 WORDS)


Higher susceptibility to Fas ligand induced apoptosis and altered modulation of cell death by tumor necrosis factor-alpha in periarticular tenocytes from patients with knee joint osteoarthritis.
The aim of the present study was to investigate the expression of Fas in periarticular tenocytes of patients with osteoarthritis (OA) and to study their susceptibility to Fas ligand-mediated apoptosis. Tendon samples were obtained from the quadriceps femoris muscle of patients with knee OA and used for histological evaluation, for immunohistochemical detection of Fas, and to establish tenocyte cultures. The expression of Fas mRNA was determined by quantitative PCR. Levels of soluble Fas and soluble tumour necrosis factor (TNF) receptor I were measured using ELISA. Apoptosis was induced with recombinant human Fas ligand and measured by a histone fragmentation assay and flow cytometry. The effects of TNF-alpha were studied by stimulation with TNF-alpha alone or 24 hours before the induction of apoptosis. Tendon samples from non-OA patients were used as controls. Histological evaluation revealed degenerative changes in the tendons of all OA patients but not in the controls. Fas was detected by immunohistochemistry in all specimens, but quantitative PCR revealed significantly higher levels of Fas mRNA in OA tenocytes. In contrast, lower levels of soluble Fas were found in OA tenocytes by ELISA. OA tenocytes were significantly more susceptible to Fas ligand induced apoptosis than were control cells. TNF-alpha reduced the Fas ligand induced apoptosis in OA tenocytes but had no effects on control tenocytes. These data suggest that knee OA is associated with higher susceptibility of periarticular tenocytes to Fas ligand induced apoptosis because of higher expression of Fas but lower levels of apoptosis-inhibiting soluble Fas. These changes may contribute to decreased cellularity in degenerative tendons and promote their rupturing. The antiapoptotic effects of TNF-alpha in OA tenocytes most likely reflect regenerative attempts and must be taken into account when anti-TNF strategies are considered for OA.


Use of autologous blood-derived endothelial progenitor cells at point-of-care to protect against implant thrombosis in a large animal model.
Titanium (Ti) is commonly utilized in many cardiovascular devices, e.g. as a component of Nitinol stents, intra- and extracorporeal mechanical circulatory assist devices, but is associated with the risk of thromboemboli formation. We propose to solve this problem by lining the Ti blood-contacting surfaces with autologous peripheral blood-derived late outgrowth endothelial progenitor cells (EPCs) after having previously demonstrated that these EPCs adhere to and grow on Ti under physiological shear stresses and functionally adapt to their environment under flow conditions ex vivo. Autologous fluorescently-labeled porcine EPCs were seeded at the point-of-care in the operating room onto Ti tubes for 30 min and implanted into the pro-thrombotic environment of the inferior vena cava of swine (n = 8). After 3 days, Ti tubes were explanted, disassembled, and the blood-contacting surface was imaged. A blinded analysis found all 4 cell-seeded implants to be free of clot, whereas 4 controls without EPCs were either entirely occluded or partially thrombosed. Pre-labeled EPCs had spread and were present on all 4 cell-seeded implants while no endothelial cells were observed on control implants. These results suggest that late outgrowth autologous EPCs represent a promising source of lining Ti implants to reduce thrombosis in vivo.


Structural principles within the human-virus protein-protein interaction network.
General properties of the antagonistic biomolecular interactions between viruses and their hosts (exogenous interactions) remain poorly understood, and may differ significantly from known principles governing the cooperative interactions within the host (endogenous interactions). Systems biology approaches have been applied to study the combined interaction networks of virus and human proteins, but such efforts have so far revealed only low-resolution patterns of host-virus interaction. Here, we layer curated and predicted 3D structural models of human-virus and human-human protein complexes on top of traditional interaction networks to reconstruct the human-virus structural interaction network. This approach reveals atomic resolution, mechanistic patterns of host-virus interaction, and facilitates systematic comparison with the host's endogenous interactions. We find that exogenous interfaces tend to overlap with and mimic endogenous interfaces, thereby competing with endogenous binding partners. The endogenous interfaces mimicked by viral proteins tend to participate in multiple endogenous interactions which are transient and regulatory in nature. While interface overlap in the endogenous network results largely from gene duplication followed by divergent evolution, viral proteins frequently achieve interface mimicry without any sequence or structural similarity to an endogenous binding partner. Finally, while endogenous interfaces tend to evolve more slowly than the rest of the protein surface, exogenous interfaces--including many sites of endogenous-exogenous overlap--tend to evolve faster, consistent with an evolutionary "arms race" between host and pathogen. These significant biophysical, functional, and evolutionary differences between host-pathogen and within-host protein-protein interactions highlight the distinct consequences of antagonism versus cooperation in biological networks.


Congenital stage 1 neuroblastoma evolved into stage 4s.
A newborn with a prenatally detected adrenal mass underwent complete resection of a stage 1 favorable histology neuroblastoma (NB) without MYC-N amplification. Two months later, the infant presented with a local recurrence and multiple hepatic metastases. Close follow-up without therapy was adopted for stage 4s NB. Enlarging tumor lesions were seen until the child was 8 months old, followed by later decrease in size. At 36 months of follow-up, the child is alive and disease-free. We describe this case of NB and its abnormally short evolution from stage 1 to stage 4s, despite initial surgery. Its spontaneous regression may help us understand the natural history of congenital NB.


Thermally Induced Modifications of a High Power cw Laser Beam.
The problem of beam-induced thermal modifications of a high powered cw laser beam is considered. The extent and type of modification depend principally upon the nature of the medium (liquid or air) and whether an external flow field is present. These conditions determine the dominant heat loss mechanism operating the fluid: forced convection, free convection, and diffusion and, thus, the beam distortions. All three cases are analyzed and figures presented, showing the type of distortion expected as determined within the framework of geometric optics.


Distribution of Mycoplasma haemofelis in blood and tissues following experimental infection.
The aim of the study was to describe blood and tissue copy number distribution during Mycoplasma haemofelis infection and determine if sequestration of organisms in body tissues could explain blood copy number cycling in infected cats. Thirteen domestic-shorthaired cats were used. Blood samples were regularly collected, and at a differing time point post-infection for each cat, tissue samples also collected, for quantitative PCR (qPCR). Absolute haemoplasma copy numbers were calculated for all blood and tissue samples, as well as an estimation of the ratio of tissue haemoplasma copy number to that expected in the tissue if a positive qPCR result arose due to tissue blood supply alone. Cats with high or moderate M. haemofelis blood copy numbers at the time of tissue collection had fewer M. haemofelis copies in most tissues than expected due to the tissue blood supply alone; only splenic and lung tissues consistently contained more M. haemofelis. However tissues collected from cats at a time of very low M. haemofelis blood copy numbers, when putative copy number cycling nadirs were occurring, were usually qPCR negative. Hence no evidence of significant tissue M. haemofelis sequestration was found in this study to explain the copy number cycling reported with this feline haemoplasma species.


Detecting Target Objects by Natural Language Instructions Using an RGB-D Camera.
Controlling robots by natural language (NL) is increasingly attracting attention for its versatility, convenience and no need of extensive training for users. Grounding is a crucial challenge of this problem to enable robots to understand NL instructions from humans. This paper mainly explores the object grounding problem and concretely studies how to detect target objects by the NL instructions using an RGB-D camera in robotic manipulation applications. In particular, a simple yet robust vision algorithm is applied to segment objects of interest. With the metric information of all segmented objects, the object attributes and relations between objects are further extracted. The NL instructions that incorporate multiple cues for object specifications are parsed into domain-specific annotations. The annotations from NL and extracted information from the RGB-D camera are matched in a computational state estimation framework to search all possible object grounding states. The final grounding is accomplished by selecting the states which have the maximum probabilities. An RGB-D scene dataset associated with different groups of NL instructions based on different cognition levels of the robot are collected. Quantitative evaluations on the dataset illustrate the advantages of the proposed method. The experiments of NL controlled object manipulation and NL-based task programming using a mobile manipulator show its effectiveness and practicability in robotic applications.


Automated spectrophotometric bicarbonate analysis in duodenal juice compared to the back titration method.
We have recently evaluated a short endoscopic secretin test for exocrine pancreatic function. Bicarbonate concentration in duodenal juice is an important parameter in this test. Measurement of bicarbonate by back titration as the gold standard method is time consuming, expensive and technically difficult, thus a simplified method is warranted. We aimed to evaluate an automated spectrophotometric method in samples spanning the effective range of bicarbonate concentrations in duodenal juice. We also evaluated if freezing of samples before analyses would affect its results. Patients routinely examined with short endoscopic secretin test suspected to have decreased pancreatic function of various reasons were included. Bicarbonate in duodenal juice was quantified by back titration and automatic spectrophotometry. Both fresh and thawed samples were analysed spectrophotometrically. 177 samples from 71 patients were analysed. Correlation coefficient of all measurements was r = 0.98 (p < 0.001). Correlation coefficient of fresh versus frozen samples conducted with automatic spectrophotometry (n = 25): r = 0.96 (p < 0.001) CONCLUSIONS: The measurement of bicarbonate in fresh and thawed samples by automatic spectrophotometrical analysis correlates excellent with the back titration gold standard. This is a major simplification of direct pancreas function testing, and allows a wider distribution of bicarbonate testing in duodenal juice. Extreme values for Bicarbonate concentration achieved by the autoanalyser method have to be interpreted with caution.


Redox signaling in colonial hydroids: many pathways for peroxide.
Studies of mitochondrial redox signaling predict that the colonial hydroids Eirene viridula and Podocoryna carnea should respond to manipulations of reactive oxygen species (ROS). Both species encrust surfaces with feeding polyps connected by networks of stolons; P. carnea is more 'sheet-like' with closely spaced polyps and short stolons, while E. viridula is more 'runner-like' with widely spaced polyps and long stolons. Treatment with the chemical antioxidant vitamin C diminishes ROS in mitochondrion-rich epitheliomuscular cells (EMCs) and produces phenotypic effects (sheet-like growth) similar to uncouplers of oxidative phosphorylation. In peripheral stolon tips, treatment with vitamin C triggers a dramatic increase of ROS that is followed by tissue death and stolon regression. The enzymatic anti-oxidant catalase is probably not taken up by the colony but, rather, converts hydrogen peroxide in the medium to water and oxygen. Exogenous catalase does not affect ROS in mitochondrion-rich EMCs, but does increase the amounts of ROS emitted from peripheral stolons, resulting in rapid, runner-like growth. Treatment with exogenous hydrogen peroxide increases ROS levels in stolon tips and results in somewhat faster colony growth. Finally, untreated colonies of E. viridula exhibit higher levels of ROS in stolon tips than untreated colonies of P. carnea. ROS may participate in a number of putative signaling pathways: (1) high levels of ROS may trigger cell and tissue death in peripheral stolon tips; (2) more moderate levels of ROS in stolon tips may trigger outward growth, inhibit branching and, possibly, mediate the redox signaling of mitochondrion-rich EMCs; and (3) ROS may have an extra-colony function, perhaps in suppressing the growth of bacteria.


Genital Reconstructive Surgery in Females With Congenital Adrenal Hyperplasia: A Systematic Review and Meta-Analysis.
Females with congenital adrenal hyperplasia (CAH) and atypical genitalia often undergo complex surgeries; however, their outcomes remain largely uncertain. We searched several databases through 8 March 2016 for studies evaluating genital reconstructive surgery in females with CAH. Reviewers working independently and in duplicate selected and appraised the studies. We included 29 observational studies (1178 patients, mean age at surgery, 2.7 ± 4.7 years; mostly classic CAH). After an average follow-up of 10.3 years, most patients who had undergone surgery had a female gender identity (88.7%) and were heterosexual (76.2%). Females who underwent surgery reported a sexual function score of 25.13 using the Female Sexual Function Index (maximum score, 36). Many patients continued to complain of substantial impairment of sensitivity in the clitoris, vaginal penetration difficulties, and low intercourse frequency. Most patients were sexually active, although only 48% reported comfortable intercourse. Most patients (79.4%) and treating health care professionals (71.8%) were satisfied with the surgical outcomes. Vaginal stenosis was common (27%), and other surgical complications, such as fistulas, urinary incontinence, and urinary tract infections, were less common. Data on quality of life were sparse and inconclusive. The long-term follow-up of females with CAH who had undergone urogenital reconstructive surgery shows variable sexual function. Most patients were sexually active and satisfied with the surgical outcomes; however, some patients still complained of impairment in sexual experience and satisfaction. The certainty in the available evidence is very low.


Spin state and reactivity of iron(iv)oxido complexes with tetradentate bispidine ligands.
The iron(iv)oxido complex [(bispidine)FeIV[double bond, length as m-dash]O(Cl)]+ is shown by experiment and high-level DLPNO-CCSD(T) quantum-chemical calculations to be an extremely short-lived and very reactive intermediate-spin (S = 1) species. At temperatures as low as -90 °C, it decays with a half-life of approx. two minutes, and this is the reason why, so far, it remained undetected and why it is extremely difficult to trap and fully characterize this interesting and extremely efficient oxidant. The large difference in reactivity between [(bispidine)FeIV[double bond, length as m-dash]O(Cl)]+ and [(bispidine)FeIV[double bond, length as m-dash]O(MeCN)]2+ (at least two orders of magnitude), while both oxido-iron(iv) complexes have very similar structures and an S = 1 electronic ground state, is presumably due to the large difference in the energy gap between the triplet and quintet electronic states. In presence of cyclohexane as substrate, [(bispidine)FeIV[double bond, length as m-dash]O(Cl)]+ oxidizes cyclohexane with a rate that is approx. 25 times faster than the self-decay of the oxidant, and selectively leads to chlorocyclohexane in moderate yield. The S = 1 electronic ground state of [(bispidine)FeIV[double bond, length as m-dash]O(Cl)]+ and a relatively low gap to the S = 2 state (approx. 6 kJ mol-1vs. approx. 75 kJ mol-1 for [(bispidine)FeIV[double bond, length as m-dash]O(MeCN)]2+) is also predicted by DLPNO-CCSD(T) quantum-chemical calculations. The method used was benchmarked with a set of six ferryl complexes with experimentally known electronic ground states.