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The Robust and Energy Efficient Authentication Protocol works for Industrial Internet of Things. The Internet of Things (IoT) is an arising innovation and expected to give answers for different modern fields. The IoT enable connection of physical devices all around the world to the internet by collecting and sharing critical and real-time data among each other. The increment of devices increases the computational cost during data transmission between devices and towards the internet. In this paper we proposed a solution that is a multi-factor authentication protocol to enhance the protocol proposed by Li et al. For Industrial IoT by adding One Time Password (OTP) after the biometric information of the user is checked by the Gateway Node (GWN) to be able to tackle additional network attack aside from those that are overcome by Li et al. scheme. Our contribution for this project is, we proposed the solution that a multi-factor authentication protocol to enhance the protocol proposed. For Industrial IoT by adding One Time Password (OTP) after the biometric information of the user is checked by the Gateway Node (GWN) to be able to tackle additional network attack aside from those that are overcome. The idea of adding OTP is inspired by where they scheme correlates to biometric of user as well. Our proposal is lower cost than the three protocols regarding authentication overhead and computational cost perspectives. Challenges and future directions of this paper examined the security shortcomings of a client confirmation convention for WSN, which is as proposed by Chang and Le. To address the normal security shortcomings of past protocols, we proposed a strong and energy effective three-factor authentication protocol for WSN.

Mosquito-borne flaviviruses are emerging pathogens of an increasing global public health concern because of their rapid increase in geographical range and the impact of climate change. Japanese encephalitis virus (JEV) and West Nile virus (WNV) are of concern because of the risk of reemergence and introduction by migratory birds. In Singapore, human WNV infection has never been reported and human JEV infection is rare. Four sentinel vector surveillance sites were established in Singapore to understand the potential risk posed by these viruses. Surveillance was carried out from August 2011 to December 2012 at Pulau Ubin, from March 2011 to March 2013 at an Avian Sanctuary (AS), from December 2010 from October 2012 at Murai Farmway, and from December 2010 to December 2013 at a nature reserve. The present study revealed active JEV transmission in Singapore through the detection of JEV genotype II in Culex tritaeniorhynchus collected from an Avian Sanctuary. Culex flavivirus (CxFV), similar to the Quang Binh virus isolated from Cx. tritaeniorhynchus in Vietnam and CxFV-LSFlaviV-A20-09 virus isolated in China, was also detected in Culex spp. (vishnui subgroup). No WNV was detected. This study demonstrates the important role that surveillance plays in public health and strongly suggests the circulation of JEV among wildlife in Singapore, despite the absence of reported human cases. A One Health approach involving surveillance, the collaboration between public health and wildlife managers, and control of mosquito populations remains the key measures in risk mitigation of JEV transmission in the enzootic cycle between birds and mosquitoes.

Japanese encephalitis virus (JEV) and West Nile virus (WNV) are arboviruses primarily transmitted by Culex spp. mosquitoes. Birds are the primary hosts for JEV and WNV. Recent WNV outbreaks in Europe and United States and their association with migratory birds highlight the importance of understanding the feeding host preference of potential vectors for outbreak preparedness, especially in nonendemic settings. Singapore is nonendemic to JEV and WNV, but is a stopover site for migratory birds of the East Asian-Australasian Flyway. Therefore, we elucidated the feeding host range of Culex spp. mosquitoes captured in four natural (bird) habitats in Singapore from January 2011 to December 2012. We characterized feeding host DNA in field-caught mosquitoes using a PCR sequencing-based assay targeting the mitochondrial gene regions. Of 22,648 mosquitoes captured, 21,287 belonged to the Culex vishnui subgroup. The host DNA analysis showed that mosquitoes from the Cx. vishnui subgroup are opportunistic biters, feeding on a range of birds and mammals. Cx. vishnui subgroup, Culex sitiens and Culex bitaeniorhynchus, was primarily ornithophagic, although they fed opportunistically on mammals, including humans. Culex gelidus and Culex quinquefasciatus, in contrast, fed mainly on mammals. The presence of ornitho- and anthropophilic mosquito vectors and susceptible avian and mammalian hosts poses a risk spill-over transmission of JEV and WNV among humans, should these viruses be introduced through migratory birds and establish persistent transmission in resident birds and animal hosts in Singapore.

Roads that dissect natural habitats present risks to wildlife, creating gaps or barriers which animals have to traverse in order to move within and between their habitats. Restoring habitat connectivity can be achieved naturally by planting trees and vines to reconnect forest gaps, or artificially by creating culverts for small ground vertebrates, building overpasses for large terrestrial animals, or installing canopy bridges for arboreal fauna. The 3-km Old Upper Thomson Road borders the eastern side of the Central Catchment Nature Reserve, the largest nature reserve in Singapore, and isolates it from neighbouring forest patches. To facilitate safe crossing for tree-dwelling animals such as the critically endangered Raffles’ banded langurs (Presbytis femoralis) along Old Upper Thomson Road, two rope bridges were installed. We monitored the use of these rope bridges by vertebrates from April 2020 to August 2021 through surveillance cameras attached on one end of each bridge. A total of 64 118 videos were processed, with 6218 (9.70%) containing vertebrates. Seven species, including three primates, two squirrels and two reptiles, utilised the bridges to travel between the forests. In particular, Raffles’ banded langurs made a total of 293 successful crossings. We have shown that these rope bridges are useful for arboreal species and can complement national efforts to restore connectivity in fragmented habitats.

Background Despite increasing reports and studies about COVID-19 in children over the last nine months, there is still much to be discovered about the true incidence, clinical presentations and transmission rates in children. Fever and respiratory symptoms remain the main clinical presentations in COVID-19 positive children. Symptoms of COVID-19 in the paediatric population appear to be less severe compared to those experienced in the adult population and there is a low case fatality rate for COVID-19 in children. More recently there have been increasing reports of children with Paediatric multisystem inflammatory syndrome temporally associated with COVID-19 (PIMS). Objectives The objectives of this study were to evaluate the spectrum of clinical presentations and evolution of clinical symptoms, management and outcomes of children with laboratory confirmed COVID-19 who presented to secondary care to help guide future management of these patients. We also describe two cases of Paediatric multisystem inflammatory syndrome temporally associated with COVID-19 (PIMS). Methods Our study is a retrospective observational study which identified 21 patients aged 1 month to 18 years with positive COVID-19 PCR and 2 patients with PIMS over a 10 week period in 4 district general hospitals within Yorkshire. The main outcome measures included symptoms prior to hospital presentation, length of hospital stay and length of symptoms; investigations including Chest x-ray, CRP and blood culture, and the presence of symptomatic contacts or contacts with positive COVID-19 swab results. Results Our study demonstrated that fever, cough and reduced oral intake were the three most common clinical presentations of COVID-19 in children. Our results are tabulated for presentation but to summarise our results; 71% of the children required a period of hospital admission and of these, 80% were admitted for between 1 to 3 days. The patients who required prolonged hospital admissions were in the younger age group or had underlying medical conditions. 100% of patients who had blood cultures performed had negative blood culture results. Only 25% of patients had bilateral consolidation on chest X-ray findings. All 21 of the patients in this study were discharged home and did not require admission to intensive care. The 2 patients with PIMS were transferred to a Paediatric Intensive Care (PICU) but have since been discharged home and remain under follow up. Our study is the first to describe photophobia as a presenting feature of COVID-19 in one patient, and chest pain in a second patient. Conclusions Fever, cough and reduced oral intake were the top 3 presentations of COVID-19 in the patients included within this study. Paediatric patients who required prolonged hospital admissions (>7 days) were in the younger age group or had underlying medical conditions. This study is the first to describe photophobia as a presenting feature of COVID-19 in one patient, and chest pain in a second patient. Larger studies and more widespread testing are required to ascertain the true incidence in the paediatric population.

Background Language proficiency is crucial for doctors as they communicate with patients, peers and other healthcare professionals. Although proficiency in English is part of admission requirements, there is a gap in the knowledge of medical students’ perception of factors enhancing English language (EL) skills during training in international medical programmes (IMPs). The gap prevents educators and policy makers from helping students who struggle with communication skills during medical training. This study therefore explores the importance of English language skills from medical students’ perspectives. Methods Six focus group interviews with 24 medical students were conducted in an IMP. Data were analysed using Braun and Clarke’s framework of thematic analysis. Results Results established three themes that constitute the importance of EL skills, namely the use of EL in medical training and practice, influence of university culture in EL mastery and individual EL proficiency as perceived by medical students. Conclusions Findings of this study demonstrate how students perceived the importance of EL skills as a professional and social requirement during medical training and for future practice. It also informs that setting English language admission pre requisites needs to be complemented with opportunities to practice context specific communication skills. Thus, international medical programmes should embed diverse and inclusive strategies to support and develop medical students’ English language skills.

Avian pox is a highly contagious avian disease, yet relatively little is known about the epidemiology and transmission of Avipoxviruses. Using a molecular approach, we report evidence for a potential link between birds and field-caught mosquitoes in the transmission of Fowlpox virus (FWPV) in Singapore. Comparison of fpv167 (P4b), fpv126 (VLTF-1), fpv175-176 (A11R-A12L) and fpv140 (H3L) gene sequences revealed close relatedness between FWPV strains obtained from cutaneous lesions of a chicken and four pools of Culex pseudovishnui, Culex spp. (vishnui group) and Coquellitidea crassipes caught in the vicinity of the study site. Chicken-derived viruses characterized during two separate infections two years later were also identical to those detected in the first event, suggesting repeated transmission of closely related FWPV strains in the locality. Since the study location is home to resident and migratory birds, we postulated that wild birds could be the source of FWPV and that bird-biting mosquitoes could act as bridging mechanical vectors. Therefore, we determined whether the FWPV-positive mosquito pools (n=4) were positive for avian DNA using a polymerase chain reaction-sequencing assay. Our findings confirmed the presence of avian host DNA in all mosquito pools, suggesting a role for Cx. pseudovishnui, Culex spp. (vishnui group) and Cq. crassipes mosquitoes in FWPV transmission. Our study exemplifies the utilization of molecular tools to understand transmission networks of pathogens affecting avian populations, which has important implications for the design of effective control measures to minimize disease burden and economic loss.

Mosquito-borne flaviviruses are emerging pathogens of an increasing global public health concern because of their rapid increase in geographical range and the impact of climate change. Japanese encephalitis virus (JEV) and West Nile virus (WNV) are of concern because of the risk of reemergence and introduction by migratory birds. In Singapore, human WNV infection has never been reported and human JEV infection is rare. Four sentinel vector surveillance sites were established in Singapore to understand the potential risk posed by these viruses. Surveillance was carried out from August 2011 to December 2012 at Pulau Ubin, from March 2011 to March 2013 at an Avian Sanctuary (AS), from December 2010 from October 2012 at Murai Farmway, and from December 2010 to December 2013 at a nature reserve. The present study revealed active JEV transmission in Singapore through the detection of JEV genotype II in Culex tritaeniorhynchus collected from an Avian Sanctuary. Culex flavivirus (CxFV), similar to the Quang Binh virus isolated from Cx. tritaeniorhynchus in Vietnam and CxFV-LSFlaviV-A20-09 virus isolated in China, was also detected in Culex spp. (vishnui subgroup). No WNV was detected. This study demonstrates the important role that surveillance plays in public health and strongly suggests the circulation of JEV among wildlife in Singapore, despite the absence of reported human cases. A One Health approach involving surveillance, the collaboration between public health and wildlife managers, and control of mosquito populations remains the key measures in risk mitigation of JEV transmission in the enzootic cycle between birds and mosquitoes.

Graphical Abstract This online structured survey has demonstrated the global impact of the COVID-19 pandemic on vascular services. The majority of centres have documented marked reductions in operating and services provided to vascular patients. In the months during recovery from the resource restrictions imposed during the pandemic peaks, there will be a significant vascular disease burden awaiting surgeons. Graphical Abstract One of the most affected specialties

Bats are important reservoirs and vectors in the transmission of emerging infectious diseases. Many highly pathogenic viruses such as SARS-CoV and rabies-related lyssaviruses have crossed species barriers to infect humans and other animals. In this study we monitored the major roost sites of bats in Singapore, and performed surveillance for zoonotic pathogens in these bats. Screening of guano samples collected during the survey uncovered a bat coronavirus ({\textless}span class="jp-italic"{\textgreater}Betacoronavirus{\textless}/span{\textgreater}) in {\textless}span class="jp-italic"{\textgreater}Cynopterus brachyotis{\textless}/span{\textgreater}, commonly known as the lesser dog-faced fruit bat. Using a capture-enrichment sequencing platform, the full-length genome of the bat CoV was sequenced and found to be closely related to the bat coronavirus HKU9 species found in Leschenault's rousette discovered in the Guangdong and Yunnan provinces.

We assessed the transfer effects of training working memory strategies to a novel problem-solving task. Previous WM training studies have produced little evidence for transfer across contexts. In the current study, 64 6- to 9-year-olds were randomly assigned to one of four training conditions: semantic and rehearsal training, semantic training only, rehearsal training only, and treated control group. All training groups performed significantly better on the transfer task than the control group, but training groups did not differ significantly from each other. Implications of the findings for cognitive interventions and future WM training studies are discussed.

Past research has demonstrated that young children and nonhuman animals are able to reason by elimination (“If not A, then B”) by relying on visual cues such as seeing that one container is empty. Other research has shown that young children can solve similar, simple inferential reasoning tasks where “emptiness” is conveyed verbally through negation (e.g., “The toy is not in the box”). However, it is unclear whether these tasks involved reasoning through the disjunctive syllogism, which requires the representation of logical negation (NOT A) and disjunction (A OR B) or simpler, nondeductive strategies. In Study 1, we extended this work by investigating whether 2-year-olds can infer the location of a toy in typical two-location elimination trials, when given both affirmative and negative sentences, and more complex three-location trials, when information about emptiness was conveyed verbally and visually. Younger 2-year-olds performed significantly better on the search task when hearing affirmative than negative sentences, whereas older 2-year-olds were equally successful with both types of sentences. Study 2 examined children’s ability to use verbal negation to solve a more complex deductive task involving disjunctive syllogism. Results showed that, in this linguistic version of the disjunctive reasoning task, both 2.5- and 3-year-olds made accurate inferences about the location of a reward, unlike prior (nonlinguistic) evidence that demonstrated this ability in 3-year-olds but not in younger children. We conclude that by the end of their second year of life, children have a robust understanding of negation which they can apply in abstract reasoning.

ObjectivesTo provide a comprehensive review of flexor tendon injuries in the hand, their management, and subsequent recovery.MethodsA review of the current literature surrounding flexor tendon anatomy, injury, surgical repair, and healing was performed.ResultsThis review examines the flexor tendons of the hand and describes their anatomy, different zones of injury, surgical repair, and their regeneration and rehabilitation following injury. Adhesions, produced as part of the normal inflammatory process and their inhibitory effect on tendon function are studied. In order to address the issue of adhesions, numerous studies have examined surgical techniques, rehabilitation protocols, and the use of pharmacological and biosynthetic agents to reduce adhesions and therefore improve patient outcomes.DiscussionThe different zones of injury influence the likelihood of a good recovery following surgical repair. In particular, the presence of digital tendon sheaths in ‘Zone 2’ means that the formation of adh...

ATP-binding cassette transporter A7 (ABCA7) is expressed in the brain and has been detected in macrophages, microglia, and neurons. ABCA7 promotes efflux of lipids from cells to apolipoproteins and can also regulate phagocytosis and modulate processing of amyloid precursor protein (APP) to generate the Alzheimer's disease (AD) amyloid-β (Aβ) peptide. Genome-wide association studies have indicated thatABCA7single nucleotide polymorphisms confer increased risk for late-onset AD; however, the role that ABCA7 plays in the brain in the AD context is unknown. In the present study, we crossed ABCA7-deficient (A7−/−) mice with J20 amyloidogenic mice to address this issue. We show that ABCA7 loss doubled insoluble Aβ levels and thioflavine-S–positive plaques in the brain. This was not related to changes in APP processing (assessed by analysis of full-length APP and the APP β C-terminal fragment). Apolipoprotein E regulates cerebral Aβ homeostasis and plaque load; however, the apolipoprotein E concentration was not altered by ABCA7 loss. Spatial reference memory was significantly impaired in both J20 and J20/A7−/−mice compared with wild-type mice; however, there were no cognitive differences between J20 and J20/A7−/−mice. There were also no major differences detected in hippocampal or plaque-associated microglial/macrophage markers between J20 and J20/A7−/−mice, whereas the capacity for bone marrow-derived macrophages derived from A7−/−mice to take up oligomeric Aβ was reduced by 51% compared with wild-type mice. Our results suggest that ABCA7 plays a role in the regulation of Aβ homeostasis in the brain and that this may be related to altered phagocyte function.

The relationship between Autism Spectrum Disorder (ASD) and mealtime behavioural problems has been discussed in the United States recently, but there is limited research data on this matter in Chinese children. This study aims to evaluate the prevalence of feeding and mealtime behavioural problems in Hong Kong Chinese preschoolers with ASD using the Brief Autism Mealtime Behavior Inventory (BAMBI). Parents with children aged between 2 to 6 years old diagnosed with ASD were asked to complete a Chinese version of BAMBI, which is a validated 18-item questionnaire designed to measure mealtime behavioural problems in children with ASD. A total of 177 children were enrolled: 78.0% were boys and 22.0% were girls; the mean age was 5.0 (2.9-6.3). The survey revealed that the “limited variety” of food was the most prevalent feeding problem. Close to half of caregivers found limited food variety being problematic and affecting their daily functioning. The perception of problems by caregivers was positively correlated with the frequency of problematic feeding behaviours. These feeding behavioural problems are not alleviated by current training. We suggest concentrating specifically on addressing the feeding behaviour through a multidisciplinary approach and by incorporating dietary advice, which will be beneficial to children with ASD and their families.

Killer cell immunoglobulin-like receptors (KIR) are encoded by highly polymorphic genes that regulate the activation of natural killer (NK) cells and other lymphocyte subsets and likely play key roles in innate and adaptive immunity. Association studies increasingly implicate KIR in disease predisposition and outcome but could be confounded by unknown KIR genetic structure in heterogeneous populations. To examine this, we characterized the diversity of 16 KIR genes in 712 Northern Californians (NC) stratified by self-assigned ethnicities and compared the profiles of KIR polymorphism with other US and global populations using a reference database. Sixty-eight distinct KIR genotypes were characterized: 58 in 457 Caucasians (NCC), 17 in 47 African Americans (NCAA), 21 in 80 Asians (NCA), 20 in 74 Hispanics (NCH), and 18 in 54 "other" ethnicities (NCO). KIR genotype patterns and frequencies in the 4 defined ethnicities were compared with each other and with 34 global populations by phylogenetic analysis. Although there were no population-specific genotypes, the KIR genotype frequency patterns faithfully traced the ancestry of NCC, NCAA, and NCA but not of NCH whose ancestries are known to be more heterogeneous. KIR genotype frequencies can therefore track ethnic ancestries in modern urban populations. Our data emphasize the importance of selecting ethnically matched controls in KIR-based studies to avert spurious associations.

Background The level of interest in general surgery among US seniors has been declining; however, it may be perceived as a more attractive career outside the United States. Methods A survey was developed and distributed to students at medical schools in 8 countries. Results were analyzed to determine whether interest in general surgery was related to sex of the respondent or economic standing of the country. Results We noted differences in the level of interest in general surgery, ranging from 8% in Italy to 58% in India. As in the United States, there was a difference in the level of interest between sexes, with a male preponderance. Students from economically less developed countries expressed a greater interest in general surgery compared with students from countries with high development. Conclusions Our study suggested the level of interest for general surgery may depend on the sex and the location of the student. Further comparison studies may suggest means to stimulate student interest in the field.

Objective: To evaluate evidence-based practice (EBP) in musculoskeletal physiotherapy and to identify barriers that exists to its implementation. Materials and Methods: A personal selection of 44 relevant papers were used to undertake this assessment. Results: The literature questions whether the sole driver for EBP must be randomised controlled trials, or whether anecdotal evidence or pragmatic trials should contribute. Barriers to the implementation of EBP have been identified including clinicians' appraisal skills and the necessary organisational changes required. Conclusions: Despite EBP having a significant influence on health policy in the UK, practitioners face various challenges when introducing and sustaining appropriate changes to practice.

Objective: To investigate whether passive joint mobilisation is beneficial if added to a home-care programme when managing patients with adhesive capsulitis of the shoulder who have received corticosteroid injection. Design: Quantitative, single-blinded, experimental, pilot study. Subjects were incidentally sampled and randomised into two groups: the control group (home-care programme), and an experimental group (which in addition received passive mobilisation of the shoulder, weekly, for 6 weeks). All subjects were assessed over a 10-week period. Setting: The physiotherapy department at Stockport Primary Care Trust. Participants: Fourteen subjects, mean age of 54.8 years. All subjects presented with shoulder capsulitis associated with trauma. The mean duration of symptoms was 2.4 months. Main outcome measures: Pain as evaluated by a Visual Analogue Scale (VAS). Secondary measures were shoulder function as evaluated by the Shoulder Pain And Disability Index (SPADI) and active range of motion (ROM...

Humans and long-tailed macaques (Macaca fascicularis) interface in several locations in Singapore. We investigated six of these interface zones to assess the level of conflict between the two species. We observed macaque-to-human interactions and distributed questionnaires to residents and visitors of nature reserves. We observed an average of two macaque-to-human interactions per hour at the sites, which included affiliative or submissive behaviors (46.9%), aggression (19.1%), taking food and other items (18.5%) searching bins, cars, and houses (13.4%), and nonaggressive contact (2.1%). Two-thirds of interactions occurred when a human was carrying food or food cues, and one-quarter occurred when a human provoked macaques. Only 8% of interactions occurred without a clear human-triggered context. Our interview showed one-third of respondents experienced nuisance problems from macaques. They had items taken from them (50.5%) and received threats (31.9%). Residents reported more nuisance problems than visitors, and their perceptions toward macaques differed. Residents were more aware of the consequences of food provisioning and that there were regulations against feeding. Residents fed macaques less and held more negative sentiments toward macaques. Nearly half of the interviewed people held neutral attitudes toward macaques and only 26.2% of respondents thought conflict with macaques warranted urgent action. Nearly two-thirds of the respondents supported education programs to ameliorate human-macaque conflict, and less than 15% supported removing or eradicating macaques. 87.6% felt that it is importance to conserve and protect macaques. Our results show that human-macaque conflict exists in Singapore, but that it may not be severe. Human behavior is largely responsible for macaque-to-human interactions, and thus could be lessened with management of human behavior in interface zones (i.e. restrict food carrying and provocation). Moreover, our interviews shows people living in Singapore value macaques, do not wish them entirely removed, prefer education-based solutions, and consider conservation and protection of them important.

The long-tailed macaque (Macaca fascicularis) population of the island-state of Singapore consists of ca. 1,218–1,454 individuals. About seventy percent of the population (ca. 1,027 individuals) is concentrated in both Bukit Timah and Central Catchment Nature Reserves, a system of reservoirs and forest reserves located in the center of Singapore. This core population resides mainly along perimeter forest areas of the reserve system, which is bordered by residential and recreational areas (e.g., parks and golf courses) and encircled by expressways. Periphery sub-populations (ca. 427 individuals) persist in forest fragments throughout Singapore mainland and on 5 offshore islands. Much of the Singaporean macaque population overlaps with human settlement and these commensal groups are mainly distributed close to roads, parks and residential areas. At least 70% of these groups are habituated to human presence and at least 50% to food provisioning. Moreover, commensal groups have more individuals and have higher infant:adult female ratios than non-commensal groups. The close association of habituated macaque groups living in human environments has led to increasing human-macaque conflict in Singapore. The overlap is also associated with human-induced population loss resulting from road accidents (2.4%); and trapping efforts (14%) aimed at ameliorating conflict issues. Consequently, it is important to better understand how humans are affecting macaque populations. In order to mitigate human-macaque conflict and at the same maintain a sustainable macaque population in Singapore, there is an urgent need for wildlife management strategies aimed at minimizing the extent of human–macaque conflict. Such strategies should include designing appropriate buffers around reserve areas, revised urban development plans, and managing the behavior of people interfacing with macaques.

In this article, a systematic approach is presented which allows the estimation of model parameters including isotherm parameters for equilibrium-dispersive and general rate models including a procedure for how to subsequently select the most appropriate isotherm and model for a given application. The approach consists of three parts: determination of feed concentration, parameter estimation, and model selection. Accurate modeling of any separation process depends on the starting point, i.e. the feed and the feed concentration, however, for many chromatographic separations, this concentration is unknown. The first part of this work therefore presents a systematic procedure for feed concentration determination. The estimation of isotherm or other model parameters is done using the simulation and optimization tool gPROMS. Finally, the predictions from each model alternative are then compared using fractionation and maximum purification diagrams. The estimation approach is successfully applied to three case studies, including purification of alcohol dehydrogenase from a yeast homogenate supernatant and gradient elution ion-exchange of myoglobin, which illustrate the approach and the relative suitability and range of application of the models in describing the behavior of complex chromatographic separations. It is found that, while the equilibrium-dispersive model is a good approximation in most cases, there are cases when the more detailed general rate model is required. © 2008 American Institute of Chemical Engineers AIChE J, 2008

Expanded criteria donor (ECD) kidney allocation aims to increase utilization and facilitate placement. We implemented an ECD program for pre-consented candidates and studied whether ECD allocation decreased cold ischemia time and delayed graft function (DGF). We compared donor, recipient and transplant data for ECD transplants performed during the first year of our program to those performed in the preceding 5 1/2 years. Logistic regression identified risk factors for DGF. Of 356 candidates, 107 (30%) consented, 32 (9%) completed evaluation and 20 (6%) underwent ECD transplantation during the program's first year. The recent and historical ECD cohorts had similar donor and recipient characteristics, except that recent ECD recipients were older. The rate of donor kidney biopsy dropped from 85% to 24% (p0.001). Cold ischemia time decreased from 16.4 to 7.4 h (p0.001), as did the incidence of DGF from 43% to 15% (p = 0.031). Three independent risk factors for DGF emerged: recipient height (OR 1.21/10 cm; p = 0.008),4 HLA mismatches (OR 20.46; p = 0.0033) and cold ischemia time (OR 1.24/h; p = 0.0036). We conclude the ECD designation provides a description of kidney quality that may obviate biopsy. ECD allocation decreased cold ischemia time and DGF, which may improve graft survival.

The use of copper wire for wire bonding integrated circuits (ICs) has increased significantly in recent years, driven mainly by the dramatic increase in the cost of gold. The technical advantages and limitations, particularly with respect to reliability, of copper for wire bonding, compared with gold, have been widely reported. This paper describes reliability studies comparing on copper, palladium coated copper and gold wires using a dedicated test vehicle comprising a modular test chip with multiple daisy chains and corrosion sensors in a BGA package. The reliability tests were High Temperature Storage (HTS), 1000 hours at 150 oC, Thermal cycling (TC) from 1000 cycles from −40 oC to + 125 oC, Temperature Humidity Bias (THB), 1000 hours at 85oC/85% RH, 20 V applied, and unbiased HAST. It was found that performance was strongly dependent on the wire type and mold compound. Copper wires with one mold compound having a higher chlorine level (12mmm), showed high leakage currents and rates of failure during THB. Both copper and palladium coated copper wires with a different mold compound showed high rates of failure during thermal cycling.

The objective of this research is to provide an improved automated computational tool to study aphasic production. Using the speech production of Italian aphasic patients, the present study demonstrates the possibility of applying an integrated algorithm to automatically assess and generate error patterns typical of aphasic speech. Philological studies and aphasia studies share one common point: errors (or variants) are informative, and the intention of the authors (in the case of philology) or of the patients (in the case of aphasiology) is to be established. For this precise reason, the present study adapts a tool, originally used in computational philology for the alignment of textual variants (Boschetti, 2007, 2008), and puts it to use for assessing aphasic patient's speech error patterns. As is demonstrated, this tool is effective and analytical. The authors expect this to be beneficial for the use of analysing aphasic production in both clinical and academic settings.

Single-column chromatography is widely used in the biopharmaceutical industries, although multi-column alternatives in the form of simulated moving bed (SMB) processes are now emerging. It may be difficult, however, to determine which column alternative will be best suited for a given application, and this work sets out to address this issue. A systematic approach is presented that is based on a full economic appraisal of each process alternative based on an optimization of the net annual profit. Single-column processes with and without recycling are considered, as are both the SMB and the Varicol process. The cyclic steady state for the SMB and Varicol processes is determined directly by complete discretization. The approach is applied to a case study based on a linear isotherm where it is found that for this particular system, a recycling policy is not necessary for the single column. When comparing the single-column process with the multi-column alternatives, the single column is the most economical provided the life time of the project is short; however, the economic benefits of the more capital-intensive multi-column processes are greater if the life time of the project is over 5 years. The SMB process is found to perform marginally better than the Varicol process over 15 years; however, this may be because not all extra degrees of freedom for the Varicol process were considered.

Objective The purpose of this study was to determine whether or not genetic amniocentesis is warranted when isolated choroid plexus cysts (CPC) or echogenic cardiac foci (EF) are noted on prenatal ultrasound. Study Design We performed a retrospective analysis on patients from our perinatal database. All obstetric patients with CPC or EF noted on second-trimester perinatology ultrasound from April, 1998 to November, 2004 were included. Information regarding ultrasound findings and neonatal outcome were analyzed. Results During the study period, 515 patients with CPC or EF were evaluated. Of these, 429 (83.3%) had isolated CPC or EF and 86 (16.7%) had additional risk factors. The incidence of abnormal karyotype was 0 versus 2.3%, respectively ( P = .03). The additional risk factors considered were: advanced maternal age, abnormal serum triple marker screening, and/or other abnormal ultrasound findings. Furthermore, during the study period there were 20,122 live births and 27 (0.1%) cases of aneuploidy diagnosed postnatally. Of these, none had isolated CPC or EF on prenatal ultrasound. Conclusion CPC or EF noted on prenatal ultrasound warrants referral for careful consultative ultrasound evaluation. In the absence of other risk factors, however, genetic amniocentesis for isolated CPC or EF does not appear to be necessary.

This study investigates the effect of renal artery multiplicity on donor and recipient outcomes after laparoscopic donor nephrectomy. Three-hundred and sixty-one sequential procedures were performed over a 4-year period. Forty-nine involved accessory renal arteries; of these, 36 required revascularization and 13 were small polar vessels and ligated. The 312 remaining kidneys with single arteries served as controls. Study variables included operative times, blood loss, hospital stay, graft function and donor and recipient complications. Kidneys with multiple revascularized arteries had a longer mean warm ischemia time (35.3 vs. 29.2 min, p = 0.0003), and more ureteral complications (6/36 vs. 10/312, p = 0.0013) than single-artery controls. In contrast, ligation of a small superior accessory artery had no significant effect on donor operative time, blood loss, or complication rate while providing similar recipient graft function compared to single-artery controls. Renal artery number is important in selecting the appropriate kidney for laparoscopic procurement. Given the current excellent results with right-sided donor nephrectomy, kidneys with single arteries should be preferentially procured, irrespective of side.

The failing myocardium is characterised by energetic imbalance, reflected by reduced phosphocreatine and creatine content. These changes may contribute to cardiac dysfunction, yet mechanisms of creatine and phosphocreatine depletion are poorly understood. Creatine is taken up by the heart via the creatine transporter. We investigated the mechanisms leading to myocardial creatine depletion in heart failure. Therefore rats were subjected to chronic left coronary artery ligation (MI; n = 36) or to sham operation (sham; n = 25). After 8 weeks, hearts were perfused with 14C-creatine buffer to determine creatine uptake rates via the creatine transporter. Total creatine content was determined by HPLC. Creatine transport in sham hearts followed Michaelis-Menten kinetics with a V(max) of 5.9 +/- 0.5 nmol/min per gww. Heart failure led to a significant 30% decrease in intracellular creatine content and to a significant 26% reduction in creatine uptake (V(max) in MI 4.3 +/- 0.4 nmol/min per gww; P < 0.001 vs. sham). We conclude that depletion of creatine/phosphocreatine content in the failing heart is due to reduced sarcolemmal creatine uptake. The creatine transporter may be a potential therapeutic target to prevent energetic imbalance in heart failure.

Contains fulltext : 57760.pdf (Publisher’s version ) (Closed access) We generated a knockout mouse model for guanidinoacetate N-methyltransferase (GAMT) deficiency (MIM 601240), the first discovered human creatine deficiency syndrome, by gene targeting in embryonic stem cells. Disruption of the open reading frame of the murine GAMT gene in the first exon resulted in the elimination of 210 of the 237 amino acids present in mGAMT. The creation of an mGAMT null allele was verified at the genetic, RNA and protein levels. GAMT knockout mice have markedly increased guanidinoacetate (GAA) and reduced creatine and creatinine levels in brain, serum and urine, which are key findings in human GAMT patients. In vivo (31)P magnetic resonance spectroscopy showed high levels of PGAA and reduced levels of creatine phosphate in heart, skeletal muscle and brain. These biochemical alterations were comparable to those found in human GAMT patients and can be attributed to the very similar GAMT expression patterns found by us in human and mouse tissues. We provide evidence that GAMT deficiency in mice causes biochemical adaptations in brain and skeletal muscle. It is associated with increased neonatal mortality, muscular hypotonia, decreased male fertility and a non-leptin-mediated life-long reduction in body weight due to reduced body fat mass. Therefore, GAMT knockout mice are a valuable creatine deficiency model for studying the effects of high-energy phosphate depletion in brain, heart, skeletal muscle and other organs.

Curcumin (CUR), the active chemical of the Asian spice turmeric, has strong anti-oxidant and anti-inflammatory properties. CUR inhibits proliferation and growth of several cell types, e.g. cancer cells. While CUR inhibitory effects on microglial cells are demonstrated, little is known of its effects on neuroglia, astrocytes (AST) and oligodendrocytes (OLG). Our work focuses on CUR's effects on neuroglial proliferation and growth in vitro, utilizing C-6 rat glioma 2B-clone cells, a mixed colony of both neuroglial cells, in 6 day trials.The doses studied included 4, 5, 10, 15, and 20 microM - concentrations slightly smaller than those shown to stimulate protein expression in ASTs. Automated particle counter was used to determine proliferation, and marker enzyme assays were used to determine AST and OLG activity.CUR inhibited neuroglial proliferation, with the degree of inhibition correlated directly with the CUR concentration. Proliferative inhibition was observed after a concentration as low as 5 microM by day 6, while inhibition of 20 microM doses occurred by day 2 of culture. Proliferative inhibition is associated with morphological changes, e.g. cell elongation and neurite prolongation, and increased activity of a marker enzyme corresponding to differentiation of OLG and with a reduced activity of the marker enzyme for AST.Our data suggests CUR acts continuously over a period of time, with low doses being as effective as higher doses given a longer period of treatment. It has been suggested that CUR's anti-inflammatory and anti-oxidant actions may be useful in the prevention-treatment of neurodegenerative diseases, e.g. Alzheimer's and Parkinson's Diseases. Given neuroglial involvement in these diseases, and CUR's observed actions on neuroglia, the data presented here may provide further explanations of CUR's preventative-therapeutic role in these diseases.

The intracellular creatine concentration is an important bioenergetic parameter in cardiac muscle. Although creatine uptake is known to be via a NaCl-dependent creatine transporter (CrT), its localization and regulation are poorly understood. We investigated CrT kinetics in isolated perfused hearts and, by using cardiomyocytes, measured CrT content at the plasma membrane or in total lysates. Rats were fed control diet or diet supplemented with creatine or the creatine analog β-guanidinopropionic acid (β-GPA). Creatine transport in control hearts followed saturation kinetics with a Kmof 70 ± 13 mM and a Vmaxof 3.7 ± 0.07 nmol · min−1· g wet wt−1. Creatine supplementation significantly decreased the Vmaxof the CrT (2.7 ± 0.17 nmol · min−1· g wet wt−1). This was matched by an ∼35% decrease in the plasma membrane CrT; the total CrT pool was unchanged. Rats fed β-GPA exhibited a >80% decrease in tissue creatine and increase in β-GPAtotal. The Vmaxof the CrT was increased (6.0 ± 0.25 nmol · min−1· g wet wt−1) and the Kmdecreased (39.8 ± 3.0 mM). The plasma membrane CrT increased about fivefold, whereas the total CrT pool remained unchanged. We conclude that, in heart, creatine transport is determined by the content of a plasma membrane isoform of the CrT but not by the total cellular CrT pool.