In this thesis we investigate two approaches to quantum gravity. The first is the emergence of gravity from a discrete fundamental theory, and the second is the direct quantisation of gravity. For the first we develop tools to determine with relatively high accuracy the speed of propagation of information in collective modes which ultimately should give us some information about the emergent causal structure. We found a way of finding the dependence on the relative interaction strengths of the Hamiltonian and we also managed to calculate this speed in the case where the operators in the Hamitonian were not necessarily bounded. For the second approach, we investigated the phenomenology of Loop Quantum Gravity. We found that ultra light black holes (lighter than the Planck mass) have interesting new properties on top of being non-singular. First their horizon is hidden behind a Plancksized wormhole, second their specific heat capacity is positive and they are quasi-stable, they take an infinite amount of time evaporate. We investigated the dynamics of their collapse and evaporation explicitly seeing that not only was there no singularity, but there is also no information loss problem. Looking at how primordial black holes were in existence, we found that they might account for a significant portion of dark matter. And if they did, their radiation spectrum is such that the black holes in the dark matter halo of v our galaxy could be the source for the ultra high energy cosmic rays we observe on earth.


This paper describes the Information Systems Groups at the Australian Defence Force Academy (ADFA), The Australian National University (ANU), and the University of Canberra (UC). Each group has a distinctive background that reflects its position in Canberra, Australia's seat of federal government. ADFA is essentially a private university for the Australian Defence Organization; ANU was set up to be a national research institution; and the UC group for many years focused on meeting the training needs for computing professionals for the federal government. Despite these distinguishing characteristics, the subject matter taught and researched in the three groups has a large degree of commonality and each group regards itself as 'vibrant' and happy with what it does. A low degree of professionalisation is perceived, however, relative to older disciplines, as there is a disjunct between what is taught as core knowledge and what is taught as research methods, a lack of social prestige, and a lack of acceptance as a discipline with a unique symbol system.


Isoelectrofocusing of superoxide dismutase (SOD) isoforms was carried out on the extracts of 117 nematode populations belonging to the so-called Xiphinema americanum -group. These populations came from the USA (77), Chile (5), Argentina (1), Venezuela (5), Portugal (15), Italy (2), Crete (1), Montenegro (1), Slovakia (4), Hungary (3), Egypt (1) and India (2). A total of 17 bands of enzyme activity were observed in the screening, whilst single enzyme phenotypes showed from two to eight bands. The high degree of SOD polymorphism of this nematode collection was grouped by cluster analysis into seven distinct homogeneous groups characterised by specific combinations of SOD markers. Sub-groups could be discriminated for larger groups. The small Groups 3 and 5 were constituted mostly by populations from USA east coast states ( i.e ., NY and PA, respectively). The larger Group 1 resulted from the association of populations coming from various and distant North American States. In other large groups, North American populations were associated with South American and European populations. Overall, the data presented here suggest that geographic separation and different hosts do not seem to be the source of genetic diversity for the X. americanum -group. When an adequate number of populations were collected from the same country, the variability expressed by such a sub-sample was comparable to that of the whole nematode collection. For the first time, homogeneous populations of a large collection of X. americanum -group populations were associated by molecular means in order to explore further approaches that may help resolve the recalcitrant taxonomy and phylogeny of this much debated group.


The study examines the role of socio-economic factors in conflict in the San community of Platfontein. This article's analysis is based on the primary data collected from individual interviews and focused group discussions conducted in 2013 and 2014. It reveals that socioeconomic factors are both the cause of the conflict and serve as remedies for the conflict. The causes date back to the historical displacement and dispossession of land the community faced. The San community is highly dependent on the limited income of a few veterans while the vast majority is unemployed. The lack of skills and limited command of the dominant language in the community makes them less able to compete for jobs. The community's economic hardships are increased by the dependency syndrome shown by the adults, who tend towards job-seeking rather than job creation and self-reliance. The economic hardship has become one formidable cause of conflict in the community. A concerted effort is needed to change the attitude of the community so that it becomes entrepreneurial and independent. One factor that erodes unity within the San community is that the leadership does not work closely with the people – a situation that increases the likelihood of conflict. The efforts undertaken to empower the San community and lift them out of poverty are very limited. The conflict between !Xun and Khwe is attributed to the divisive political rule adopted during the apartheid regime in South Africa. Comparative economic asymmetries between !Xun and Khwe are also causes of conflict. Furthermore, the widening of social distance, along with competition for jobs and housing, increases the tensions and divisions between the !Xun and Khwe communities. The cause of conflict between the San community and other communities is also associated with unemployment and unfair treatment. Socio-economic factors are valuable ingredients in the process of conflict resolution and healing the emotional problems of the conflicting parties.


A full band Monte Carlo study of the electron transport in 3C–SiC is presented based on an ab initio band structure calculation using the local density approximation to the density functional theory. The scattering rates and impact ionization transition rates have been calculated numerically from the ab initio band structure using both energy dispersion and numerical wave functions. This approach reduces the number of empirical parameters needed to a minimum. The two empirical coupling constants used have been deduced by fitting the simulated mobility as a function of lattice temperature to experimental data. The peak velocity was found to be approximately 2.2×107 cm/s with a clear negative differential mobility above 600 kV/cm. The electron initiated impact ionization coefficients were found to be 2–10 times stronger than the reported values for the hole initiated impact ionization.


A traditional codend (40 mm diamond mesh) and an experimental codend (40 mm square mesh) made of 2.6 mm diameter knotless PA netting were tested on a commercial trawl net on a sandy-muddy bottom (~70 m depth) of the Adriatic sea in order to assess the size selectivity of European hake ( Merluccius merluccius ) and the reduction of the discards in a demersal multi-species trawl fishery. The catch was sorted as target species and bycatch and the selectivity with respect to European hake was investigated using the covered codend method. The square-mesh codend allowed a reduction of about 37% of the fraction discarded at sea. The mean catch obtained with the experimental codend was lower than that obtained with the traditional codend (about 14 kg per haul) but the short-term economic losses were low (~12%). The square-mesh codend was also more selective than the traditional codend, giving the juveniles of European hake a good chance of escape: the mean selection length (L 50 ) was 7.60 cm in DM and 12.98 cm in SM. Moreover, the mesh configuration did not affect the gear's performance. Thus, the square-mesh codend could be an easy, inexpensive and useful solution for a more sustainable management of the resources in Adriatic multi-species fishery.


—Our approach to laboratory education in power electronics and electric machines is presented. The approach centers upon "blue-box" laboratory components, that aid the student in rapid experiment assembly without disguising important aspects of the hardware. Several example experiments are presented. Schematics and construction techniques for the hardware are publicly available.


Acinar cell carcinoma (ACC) is a rare pancreatic malignancy with distinctive clinical, molecular, and morphological features. The long-term survival of ACC patients is substantially superior to that of pancreatic adenocarcinoma patients. As there are no significant patient series about ACCs, our understanding of this illness is mainly based on case reports and limited patient series. Surgical resection is the treatment of choice for patients with the disease restricted to one organ; however, with recent breakthroughs in precision medicine, medicines targeting the one-of-a-kind molecular profile of ACC are on the horizon. There are no standard treatment protocols available for people in which a total surgical resection to cure the condition is not possible. As a result of shared genetic alterations, ACCs are chemosensitive to agents with activity against pancreatic adenocarcinomas and colorectal carcinomas. The role of neoadjuvant or adjuvant chemoradiotherapy has not been established. This article aims to do a comprehensive literature study and present the most recent information on acinar cell cancer.


Narrative politics reframes how we cultivate knowledge in the academy, foregrounding the voices of research subjects and their relationships with researchers to re-embed scholars in the social world. Narrative affects the reader's emotional capacities and fosters empathic understanding, encouraging a more human engagement with figures that have been made threatening, as Elizabeth Dauphinée explores in The Politics of Exile and Richard Jackson in Confessions of a Terrorist. Narrative politics is concerned with the question of how academics respond to the violence of war and whether the analytical tools of the social sciences are an adequate response to the human horror of war.  The narratives of peace people are particularly compelling in the way they challenge the assertions of the dominant culture of wider society and the discipline of IR. Aotearoa New Zealand has a rich history of grassroots peace movements and activities that have influenced wider society. However, their stories are not well recorded in the dominant narrative of state institutions or academia. Peace Activist Elsie Locke published Peace People, a broad historical survey of peace activism from pre-European Maori to 1975. Maire Leadbeater brings the account up to 2013 in Peace, Power and Politics. All accounts emphasise that ordinary people were at the heart of activities, organisations and movements for peace.   One of these 'ordinary' people left out of Locke and Leadbeater's accounts is Gita Brooke, co-founder of the Whanganui-based charitable trust, Peace through Unity [PTU]. As a self-identified 'peace person,' Brooke has written much about their work and been involved in peace activities in Aotearoa NZ since the 1980s. Narrative politics provides a lens in IR to explore the story of Gita Brooke as co-founder of PTU. I show the contribution PTU has made and continues to make to a culture of peace in Aotearoa New Zealand and as a worldwide network, explored through the themes of education for global citizenship, transformation through thought-work, and responsibility for local action. It examines how PTU's vision of a culture of peace has been communicated through the organisation's newsletter, Many to Many, through its involvement with the United Nations as an accredited NGO, and through its local activities. Using archival sources, data from interviews and a content analysis of the newsletter, and complemented by the lens of and insights from the discourse of narrative politics, this study suggests that PTU provides a space for critical self-reflection in the pursuit of peace that challenges the thought/action binary of institutionalised NGOs. The deterritorialised publication, Many to Many, connects peace people through a networked area of mutual agreement that is inclusive, educative and transformative.


Analysing well test data from gas-condensate reservoirs can be challenging, particularly when pressure drops below the dew point and condensate forms near the well. Usually, a single-phase pseudo-pressure approach is used to analyse the corresponding pressure transient well test data in combination with a composite reservoir model, but this approach has its shortcomings. A two-phase pseudo-pressure approach has been shown to give better results, but it requires relative permeability (kr) data which are not readily available.
 The paper demonstrates the reliability of calculating a pressure versus radius profile from pressure versus time build up data from tests on wells in gas-condensate reservoirs. The calculation is based on the probe radius concept originally proposed for single-phase systems. It also evaluates the possibility of obtaining, analytically, kr data affected by pressure and velocity in single-rate and multi-rate tests. The calculation is based on Darcy's law using the pressure derivative with respect to distance obtained from the pressure versus radius profile. The theory of these calculations is verified by comparing the results with the output from a numerical simulator based on a single-layer single-well radial reservoir model. A simple binary rich gas condensate fluid was used in the numerical simulation.
 The results demonstrate that the pressure versus radius profile using probe radius theory reasonably matches the corresponding pressure versus radius profile output from the numerical simulation. This also shows that the method can reliably predict the condensate bank radius. At first, the analytical approach used to calculate kr, as a function of radius, resulted in oscillations due to the nature of derivative calculation involved. The source of the kr noise was treated following two separate approaches that can be used depending on the level of noise versus ease of use. The calculated kr versus radius data showed good agreement with the corresponding grid block kr versus radius data predicted by the simulator for various rock types and flow rates.
 The method described in this paper provides a practical tool to estimate kr data that can be used to calculate two-phase pseudo pressure and hence potentially improve the analysis of gas-condensate test data affected by condensate banking and velocity. The derived kr data may also have other applications.


Cerebral palsy has become the number one cause of disability of children in the world today. Yet in many countries of the South there are few therapists despite the millions of children affected. Furthermore, there is little opportunity for those therapists and others working with children with cerebral palsy to undergo specialist training. Cerebral palsy is a challenging condition which presents itself differently in every child. This book enables those working with children who suffer from cerebral palsy to make the necessary decisions and choose the appropriate therapeutic activities for each individual child. The author closely integrates the theory with practical skills, reminding readers of the theory behind the practice and providing opportunities to reflect on what has been learnt. The book provides sets of principles by which to observe and analyse a child's problems and then plan treatment. Many illustrated examples of how to apply these principles are given throughout the book. However readers are urged to understand that these examples are not to be considered as recipes: each child is different and what works for one may not work for all. The book has been written for therapists but the clear line illustrations, glossary and minimal use of technical terms will ensure that parents and community workers will also find the book useful and informative.


INTRODUCTION
Goal setting is an integral part of the rehabilitation process and assists occupational therapists to target therapy towards achieving meaningful outcomes. People with mild cognitive impairment or dementia may experience barriers participating in goal setting due to preconceptions that the person cannot participate owing to changes in both cognitive and communicative abilities. The aim of this review was to identify goal setting approaches, common goals identified, and enablers and barriers to goal setting for people with mild cognitive impairment or dementia participating in specific rehabilitation programmes.

METHODS
Four electronic databases were searched in April 2020 for English language articles that described goal setting processes during a rehabilitation programme for people with mild cognitive impairment or dementia. Studies of all designs were included. Two authors screened citations and full text articles. Data were extracted, synthesised, and presented narratively.

RESULTS
Twenty-seven studies met the eligibility criteria. Both structured and nonstructured goal setting methods were used with common tools including the Canadian Occupational Performance Measure, the Bangor Goal Setting Interview and Goal Attainment Scaling. The nature of goals tended to depend on the scope of the rehabilitation programme in which the person was involved. Goal setting was more difficult for people with more advanced symptoms of dementia and when staff lacked skills and experience working with people with dementia. Use of a structured approach to goal setting, establishment of therapeutic rapport, individualisation of goals, and family involvement were reported to be beneficial.

CONCLUSION
Collaborative goal setting is a foundation of rehabilitation for people with dementia and should not be avoided due to preconceptions that the person cannot participate. Results suggests that occupational therapists can use a number of strategies to maximise participation and engagement and play a pivotal role in upskilling staff to enable effective goal setting for people with mild cognitive impairment or dementia.


Abstract Objective Hearing loss is an important health concern in Canada's Arctic. The objective of this research was to provide information on the prevalence of childhood hearing loss in Nunavut. Design This cross-sectional study involved comprehensive audiologic assessments of school-aged children in six communities to determine overall and community-specific prevalence of hearing loss. Data were collected about hearing aid use and factors affecting use through a parent questionnaire. Study sample Assessments were completed for 644 children in kindergarten to grade 6. Results 124 (19.3%) children had hearing loss of ≥ 30 dB HL at one or more frequencies in at least one ear (93.5% conductive loss). Applying a Canadian prevalence study definition, 148 (23.5%) children had hearing loss. Tympanic membrane perforations were present in 36.8% (n = 28) of children with unilateral and 45.8% (n = 22) with bilateral loss. Conclusions The prevalence of hearing loss in Canada's North was almost three times that reported for non-indigenous children. One in five school-aged children was found to have hearing loss that is likely to affect classroom learning and social/emotional development. A hearing health strategy tailored to this population is critically needed.


ISC-Aermod view dispersion model has been used to study the ground level concentration of hydrocarbon (HC). The purpose was to predict the air quality effects from off-grid diesel power generators operated by a textile factory in Lagos, Nigeria on its host airshed. Emissions from 22 point sources in 5 sections of the factory were considered with 6 different scenarios. 4 years of hourly meteorological observations were used for the investigation of dispersion. The model output showed the highest value of maximum ground level concentration at 90 m south east of the factory. The predicted impact using the worst case scenario showed that the ambient HC of the host air shed will change by 0.01-0.05% of Nigeria's Federal Ministry of Environment (FMENV) standard. HC emissions from factory will not significantly affect the host air shed as the maximum concentrations from the worst case scenario were still lower than the national standard. However, since emissions from other factories will also be released into the same host environment, an integrated approach factoring the contributions from other factories should be employed in host air quality management.


ObjectiveThe authors prospectively studied the impact of immediate breast reconstruction on patients undergoing mastectomy. Summary Background DataDespite the advocation of a breast-conserving approach to the treatment of breast cancer, many women continue to medically require or choose mastectomy for the treatment of breast cancer. In recent years, immediate breast reconstruction has become an alternative to either mastectomy alone or to delayed reconstruction. MethodsA prospective database of 216 patients who underwent mastectomy with immediate reconstruction was established. In this series, 94 procedures involved implants or tissue expanders, and 124 tissue transfers were performed. ResultsThe overall complication rate was 15.3%; only 9% of patients who underwent autologous tissue transfers required secondary procedures. When implants were performed, the overall rate of prosthetic loss was 8%. The majority of patients (n = 101) underwent transverse rectus abdominis musculocutaneous (TRAM) flaps. Twenty-six of the 38 (17.5%) patients who required transfusion were from this group. Partial flap losses in this group (7%) were correlated to a history of heavy smoking. With a median follow-up of 33.2 months, only two patients had recurred locally. According to patient opinion, autologous tissue transfers resulted in a statistically better cosmetic result. ConclusionsImmediate reconstruction can be performed safely and with excellent cosmetic results.


Structured sentiment analysis attempts to extract full opinion tuples from a text, but over time this task has been subdivided into smaller and smaller sub-tasks, e.g., target extraction or targeted polarity classification. We argue that this division has become counterproductive and propose a new unified framework to remedy the situation. We cast the structured sentiment problem as dependency graph parsing, where the nodes are spans of sentiment holders, targets and expressions, and the arcs are the relations between them. We perform experiments on five datasets in four languages (English, Norwegian, Basque, and Catalan) and show that this approach leads to strong improvements over state-of-the-art baselines. Our analysis shows that refining the sentiment graphs with syntactic dependency information further improves results.


As Americans we pride ourselves on the rule of law and its sine qua non, an independent judiciary. In The Federalist No. 78, Alexander Hamilton described judicial independence as "an essential safeguard against the effects of occasional ill humors in the society." (1) In the course of reaffirming the special role of judicial independence in our own society, we routinely decry the "telephone justice" practiced in some parts of the world. (2) Before the Berlin Wall came down, crimes such as "infringing on the activities of the state" served as "the fig leaves of a system that didn't disguise its real purpose: executing the wishes of the state's Communist Party leadership and their secret police." (3) Even as the world enters the twenty-first century, there are still nations where a judge can expect to receive a call from a party boss or security officer with orders on how to decide a case. (4) While most would agree that such overt interference is the antithesis of judicial independence, these are the easy cases. The essence of telephone justice is decision-making on grounds external to the judge's own assessment of the law and the facts of a case. This evil may appear in many subtle guises. Judges must resist outside influence to maintain the uncompromised impartiality our offices require. There is more to looking outside the case and the law for direction then waiting for a call from the KGB or the Stasi. Judges face external pressures every day. The temptation to pander to these external influences has never been greater. Federal judicial nomination and confirmation proceedings are openly political. (5) Judicial races are more expensive and hotly contested than ever before. (6) Media attention to court decisions has increased to the point where judges may attain celebrity status virtually overnight. (7) The siren call of celebrity and career advancement (or, for that matter, simple preservation) is difficult to resist. The need for resistance is acute, however, against a backdrop littered with fakers--"Judge Judies" who are not constrained by the code of judicial conduct; people who tarnish the judiciary's standing with the public for purposes of financial gain. (8) The first four sections of this article identify four permutations of telephone justice: pandering for confirmation, pandering to political pressure, pandering for votes, and pandering to the cameras. The final section tells the extraordinary tale that should perhaps go into the reporters as Judge Thomas Penfield Jackson v. Microsoft. I. PANDERING FOR CONFIRMATION When the Senate considered the nomination of Thurgood Marshall in 1967, the popular consensus was that candidates for the Supreme Court should not disclose their positions on substantive law. As Senator Edward M. Kennedy then said, "We are not charged with the responsibility of approving a man to be associate justice of the Supreme Court only if his views always coincide with our own." (9) Senator Kennedy has since adopted a different approach to the proper role of the Senate, (10) and the nature of Senate confirmation itself has changed. Federal judicial selection entered the modern media era in 1981, when Justice Sandra Day O'Connor's confirmation hearings were covered live by radio and television. (11) When pressured by the media to state her position on certain issues, however, Justice O'Connor demurred: I do not believe that as a nominee I can tell you how I might vote on a particular issue which may come before the Court, or endorse or criticize specific Suprem[e] Court decisions presenting issues which may well come before the Court again. To do so would mean that I have prejudged the matter or have morally committed myself to a certain position. Such a statement by me as to how I might resolve a particular issue or what I might do in a future Court action might make it necessary for me to disqualify myself on the matter. …


Semi-Definite Programming (SDP) with low-rank prior has been widely applied in Non-Rigid Structure from Motion (NRSfM). Based on a low-rank constraint, it avoids the inherent ambiguity of basis number selection in conventional base-shape or base-trajectory methods. Despite the efficiency in deformable shape reconstruction, it remains unclear how to assess the uncertainty of the recovered shape from the SDP process. In this paper, we present a statistical inference on the element-wise uncertainty quantification of the estimated deforming 3D shape points in the case of the exact low-rank SDP problem. A closed-form uncertainty quantification method is proposed and tested. Moreover, we extend the exact low-rank uncertainty quantification to the approximate low-rank scenario with a numerical optimal rank selection method, which enables solving practical application in SDP based NRSfM scenario. The proposed method provides an independent module to the SDP method and only requires the statistic information of the input 2D tracked points. Extensive experiments prove that the output 3D points have identical normal distribution to the 2D trackings, the proposed method and quantify the uncertainty accurately, and supports that it has desirable effects on routinely SDP low-rank based NRSfM solver.


The mechanical property of sintered MoSi2 materials has been investigated, based on the detailed examination of their microstructures. The nondestructive technique by an ultrasonic wave was also used for evaluating the damage behaviors of MoSi2 materials suffered from the cyclic thermal shock. MoSi2 materials were sintered at the temperature of 1723 K. The flexural strength of MoSi2 materials gradually decreased with increasing the thermal shock cycle, accompanying the extensive creation of surface cracks. The increase of thermal shock cycles resulted in a great decrease of ultrasonic wave velocity and a linear increase of attenuation coefficient for MoSi2 materials.


Over the first three months of life the infant's metabolic rate rises, which, together with the rise in ratio of mass to surface area, means that the net heat loss per unit surface area is 50% higher in a 3 month old infant than in a neonate. This, together with the thicker layer of subcutaneous fat and more effective peripheral vasomotor response to cold in a 3 month old infant, means that thermal balance is shifted in favour of heat conservation. The head is the site of 40% of heat production and of up to 85% of heat loss in an infant in bed: covers rising up over the head could therefore result in acute thermal imbalance with a rise in brain temperature not necessarily accompanied by a rise in body temperature. In animal studies relatively small changes in hypothalamic temperature have profound effects on the control of respiration. Alternatively, a rise in metabolic rate (from an acute infection, for example) could result in a significant change in thermal balance. There is anecdotal evidence that heat stress may be associated with sudden infant death or with severe hypoventilation. In the Avon studies infants with SIDS, particularly those over 70 days of age, were more heavily wrapped and were more likely to have had the heating on all night than control infants matched for age, date, and neighbourhood. There was no significant excess of viral infections in the infants with SIDS, but those who had virus infections were much more heavily wrapped than control infants with similar infections, suggesting that the combination of heavy wrapping and virus infection may be more important than either factor alone. There is, therefore, some physiological evidence that infants of 2 to 3 months of age may be more vulnerable to heat stress than younger infants, and limited evidence, from clinical studies, that this may occur and be associated with some sudden deaths. The precise contribution of thermal stress and the mechanism by which it could cause death remain unclear.


Objectives Prostate cancer is the most common cancer and the second leading cause of cancer-related deaths among men, but the contributing factors are unclear. One such may be night work because of the day/night alternation of work and the resulting disturbance of the circadian system. The purpose of the present study was to investigate the prospective relation between number of years with night work and prostate cancer in men. Design Cohort study comparing night and day working twins with respect to incident prostate cancer in 12 322 men. Setting Individuals in the Swedish Twin Registry. Participants 12 322 male twins. Outcome measures Prostate cancer diagnoses obtained from the Swedish Cancer Registry with a follow-up time of 12 years, with a total number of cases=454. Results Multiple Cox proportional hazard regression analysis, adjusted for a number of covariates, showed no association between ever night work and prostate cancer, nor for duration of night work and prostate cancer. Analysis of twin pairs discordant for prostate cancer (n=332) showed no significant association between night work and prostate cancer. Conclusions The results, together with previous studies, suggest that night work does not seem to constitute a risk factor for prostate cancer.


In this article, the first spatially resolved millennium-long summer (June–August) temperature reconstruction over the Arctic and Subarctic domain (north of 60° N) is presented. It is based on a set of 54 annually dated temperature sensitive proxy archives of various types, mainly from the updated and revised PAGES2k database supplemented with 6 new recently published proxy records. As a major novelty, an extension of the Bayesian BARCAST climate field (CF) reconstruction technique provides a means to treat climate archives with dating uncertainties. In total 1400 realisations of the temperature CF were generated, enabling further analyses to be carried out in a probabilistic framework. The new seasonal CF reconstruction for the Arctic region can be shown to be skilful for the majority of the terrestrial nodes. The decrease in the proxy data density back in time however limits the analyses in the spatial domain to the period after 750 CE, while the spatially averaged reconstruction covers the entire time interval of 1–2002 CE. The analysis of basic features of the reconstructed seasonal CF focuses on the regional expression of past major climate anomalies in order to uncover the potential of the new product for studying Common Era temperature variability in the region. The long-term, centennial to millennial, evolution of the reconstructed temperature is in good agreement with a general pattern that was inferred in recent studies for the Arctic and its sub-regions. On the pan-Arctic scale the reconstruction shows a cooling trend which is, however, statistically insignificant and the estimated magnitude of the millennial scale cooling is three times smaller than inferred in the previous studies. The trend is spatially heterogeneous and for some regions such as Greenland the reconstruction demonstrates a tendency to the warming instead. The reconstruction shows a pronounced Medieval Climate Anomaly (MCA, here, ca. ~ 960–1060 CE), which was characterised by a sequence of extremely warm decades over the whole domain. The medieval warming was followed by a gradual cooling into the Little Ice Age (LIA), with 1580–1680 CE as the longest centennial-scale cold period, culminating around 1812–1822 CE for most of the target region. At the same time there is evidence for a drastic reduction in sea-ice on the Greenland shelf, which is reflected by rather high summer temperatures over Greenland and Baffin Island during that decade. During the MCA, the contrast between reconstructed summer temperatures over mid- and high-latitudes in Europe and the European/North Atlantic sector of the Arctic shows a very dynamic expression of the Arctic amplification, with leads and lags between continental and more marine and extreme latitude settings. While our analysis shows that the peak MCA summer temperatures were as high as in the late 20th and early 21st century, the spatial coherence of extreme years over the last decades seems unprecedented at least back until 750 CE. However, statistical testing could not provide conclusive support of the contemporary warming to supersede the peak of the MCA in terms of the pan-Arctic mean summer temperatures.


Computerising building regulations to allow reasoning is one of the main challenges in automated compliance checking in the built environment. While there has been a long history of translating regulations manually, in recent years, natural language processing (NLP) has been used to support or automate this task. While rule- and ontology-based information extraction and transformation approaches have achieved accurate translations for narrow domains and specific regulation types, machine learning (ML) promises increased scalability and adaptability to new regulation styles. Since ML usually requires many annotated examples as training data, we take advantage of the long history of building code computerisation and use a corpus of manually translated regulations to train a transformer-based encoder-decoder model. Given a relatively small corpus, the model learns to predict the logical structure and extracts entities and relations reasonably well. While the translation quality is not adequate to fully automate the process, the model shows the potential to serve as an auto-completion system and to identify manually translated regulations that need to be reviewed.


IMPORTANCE
Surgical site infections (SSIs) may increase health care costs, but few studies have conducted an analysis from the perspective of hospital administrators.

OBJECTIVE
To determine the change in hospital profit due to SSIs.

DESIGN
Retrospective study of data from January 1, 2007, to December 31, 2010.

SETTING
The study was performed at 4 of The Johns Hopkins Health System acute care hospitals in Maryland: Johns Hopkins Bayview (560 beds); Howard County General Hospital (238 beds); The Johns Hopkins Hospital (946 beds); and Suburban Hospital (229 beds).

PARTICIPANTS
Eligible patients for the study included those patients admitted to the 4 hospitals between January 1, 2007, and December 31, 2010, with complete data and the correct International Classification of Diseases, Ninth Revision code, as determined by the infection preventionist. Infection preventionists performed complete medical record review using National Healthcare Safety Network definitions to identify SSIs. Patients were stratified using the All Patient Refined Diagnosis Related Groups to estimate the change in hospital profit due to SSIs.

EXPOSURE
Surgical site infections.

MAIN OUTCOMES AND MEASURES
The outcomes of the study were the difference in daily total charges, length of stay (LOS), 30-day readmission rate, and profit for patients with an SSI when compared with patients without an SSI. The hypothesis, formulated prior to data collection, that patients with an SSI have higher daily total costs, a longer LOS, and higher 30-day readmission rates than patients without an SSI, was tested using a nonpaired Mann-Whitney U test, an analysis of covariance, and a Pearson χ2 test. Hospital charges were used as a proxy for hospital cost. RESULTS The daily total charges, mean LOS, and 30-day readmission rate for patients with an SSI compared with patients without an SSI were $7493 vs $7924 (P = .99); 10.56 days vs 5.64 days (P < .001); and 51.94 vs 8.19 readmissions per 100 procedures (P < .001). The change in profit due SSIs was $2 268 589.

CONCLUSIONS AND RELEVANCE
The data suggest that hospitals have a financial incentive to reduce SSIs, but hospitals should expect to see an increase in both cost and revenue when SSIs are reduced.


Using the two-component model for charmonium production, which includes contributions from both initial hard nucleon-nucleon scattering and from regeneration in the quark-gluon plasma, we study the nuclear modification factor R{sub AA} and elliptic flow v{sub 2} of J/{psi} in relativistic heavy-ion collisions. For the expansion dynamics of produced hot, dense matter, we introduce a schematic fireball model with its transverse acceleration determined from the pressure gradient inside the fireball and azimuthally anisotropic expansion parametrized to reproduce measured v{sub 2} of light hadrons. We assume that light hadrons freeze out at the temperature of 120 MeV while charmonia freeze out at 160 MeV, similar to the kinetic and chemical freeze-out temperatures in the statistical model, respectively. For the properties of charmonia in the quark-gluon plasma, we use the screening mass between their charm and anticharm quarks and their dissociation cross sections given by the perturbative quantum chromodynamical (pQCD) calculations in the leading order and up to the next-to-leading order, respectively. For the relaxation time of charm and anticharm quarks in the quark-gluon plasma, we also use the one calculated in the leading-order pQCD. Modeling the effect of higher-order corrections in pQCD by introducing multiplicative factors to the dissociation cross sections ofmore » charmonia and the elastic scattering cross sections of charm and anticharm quarks, we find that this effect is small for the R{sub AA} of J/{psi} as they suppress the number of initially produced J/{psi} but enhance the number of regenerated ones. The higher-order corrections increase, however, the v{sub 2} of J/{psi}. Our results suggest that the v{sub 2} of J/{psi} can play an important role in discriminating between J/{psi} production from initial hard collisions and from regeneration in the quark-gluon plasma.« less


Crystallization behavior of the fresnoite-type Ba2TiGe2O8 (BTG) with a large optical nonlinearity has been examined in the BaO-TiO2-GeO2 glass thin film fabricated by a RF sputtering technique and the corresponding glass (same composition of thin film, i.e., 28BaO-22TiO2-50GeO2). Both the glass thin film and the corresponding glass were crystallized by the heat-treatment, keeping a good transparency. Initial formation of BTG phase followed by the BaGe4O9 phase was confirmed in the both glass samples. In addition, the BTG crystallites in the both glass samples indicated the preferential (211) orientation. Crystallization behavior confirmed in this study was quite different from the previous study about the 30BaO-15TiO2-55GeO2 glass.


The authors report their experience with 14 children in whom acute torticollis or a fixed flexion neck deformity developed. Other than neck deformity, there was no other significant functional or neurological symptom. Although several possible pathogenetic factors have been speculated, the exact cause remains unknown. Conservative observation and/or attempts at closed reduction failed to effect deformity resolution. Investigations revealed "locking" of facets that resulted in rotatory or translatory atlantoaxial dislocation depending on the nature of facet dislocation. The management issues in such cases are evaluated. The authors discuss the validity of atlantoaxial facet distraction and manipulation/reduction and fixation under direct visualization. In all cases recovery from neck deformity was significant immediately after surgery. The deformity resolution was sustained during a mean follow-up period of 23 months (range 3-52 months), although the range of neck movements remained marginally restricted. The craniovertebral realignment is demonstrated by images and clinical photographs.


Eukaryotic translation initiation factor 2B (eIF2B) is a master regulator of protein synthesis under normal and stress conditions. Mutations in any of the five genes encoding its subunits lead to vanishing white matter (VWM) disease, a recessive genetic deadly illness caused by progressive loss of white matter in the brain. In this study we used fibroblasts, which are not involved in the disease, to demonstrate the involvement of eIF2B in mitochondrial function and abundance. Mass spectrometry of total proteome of mouse embryonic fibroblasts (MEFs) isolated from Eif2b5R132H/R132H mice revealed unbalanced stoichiometry of proteins involved in oxidative phosphorylation and of mitochondrial translation machinery components, among others. Mutant MEFs exhibit 55% decrease in oxygen consumption rate per mtDNA content and 47% increase in mitochondrial abundance (p < 0.005), reflecting adaptation to energy requirements. A more robust eIF2B‐associated oxidative respiration deficiency was found in mutant primary astrocytes, which exhibit > 3‐fold lower ATP‐linked respiration per cell despite a 2‐fold increase in mtDNA content (p < 0.03). The 2‐fold increase in basal and stimulated glycolysis in mutant astrocytes (p ≤ 0.03), but not in MEFs, demonstrates their higher energetic needs and further explicates their involvement in the disease. The data demonstrate the critical role of eIF2B in tight coordination of expression from nuclear and mitochondrial genomes and illuminates the importance of mitochondrial function in VWM pathology. Further dissection of the signaling network associated with eIF2B function will help generating therapeutic strategies for VWM disease and possibly other neurodegenerative disorders.


Studies on chemical mechanical polishing (CMP) for silicon nitride (Si3N4) balls with CeO2 abrasive carried to investigate the mechanism of chemo-mechanical action between silicon nitride and CeO2. It is found that CeO2 is more effective to obtain smooth Si3N4 balls than other abrasives, and extremely smooth Si3N4 balls with surface Ra 4nm were obtained after polishing. XRD test is used to detect the reaction resultants on the ball surface, and the results show that SiO2 is the main resultant of the chemical reaction between Si3N4 and CeO2, and the test results confirm the correctness of thermodynamic analysis based on Gibb's free energy of formation. It is also found that water play as a key factor in CMP.


Organic–inorganic composite proton exchange membranes (PEMs) are of interest in fuel cell applications because of potential benefits in conductivity, mechanical, and transport properties that may be imparted by the inorganic component. Our previous work showed that polymeric membranes based on blends of poly(vinylidene fluoride) (PVDF) and cross-linked sulfonated acrylic polyelectrolytes (PE) compare favorably against the proton conductivity and mechanical properties of commercial perfluorosulfonic acid-based PEMs. One problem found in the previous study was that crystalline regions in homopolymers of PVDF interfered with the formation of proton conducting pathways by the PE component. In this study, we explore the ability to use proton-conductive zirconium-based inorganic particles to improve conductivity in such PVDF/PE membranes. Three different particles were considered, namely, zirconium oxide, zirconium hydroxide sulfate, and zirconium hydrogen phosphate. Dispersion of particles in the polymer matrix was limited, resulting in severe aggregation at particle loadings above 5 wt %. Nevertheless, a general improvement in proton conductivity was evidenced in composite membranes with 0.5 to 1 wt % particle loadings. This beneficial effect was particularly noticeable in membranes manufactured from highly crystalline PVDF homopolymers (7 to 14% increase). We propose that the surface of zirconium particles act to provide proton conducting pathways between PE regions that otherwise would become blocked due to PVDF crystallization. In addition to conductivity, composite membranes exhibited enhancement of tensile properties at identical particle loadings, especially in membranes containing more flexible PVDF:HFP copolymers, where a reinforcing stiffening effect was evident (19 to 22% elastic modulus increment). © 2012 Wiley Periodicals, Inc. J Appl Polym Sci, 2012


Increased precipitation is one projected outcome of climate change that may enhance the discharge of freshwater to the coastal zone. The resulting lower salinity, and associated discharge of both nutrients and dissolved organic carbon, may influence food web functioning. The scope of this study was to determine the net outcome of increased freshwater discharge on the balance between auto‐ and heterotrophic processes in the coastal zone. By using long‐term ecological time series data covering 13 years, we show that increased river discharge suppresses phytoplankton biomass production and shifts the carbon flow towards microbial heterotrophy. A 76% increase in freshwater discharge resulted in a 2.2 times higher ratio of bacterio‐ to phytoplankton production (Pb:Pp). The level of Pb:Pp is a function of riverine total organic carbon supply to the coastal zone. This is mainly due to the negative effect of freshwater and total organic carbon discharge on phytoplankton growth, despite a concomitant increase in discharge of nitrogen and phosphorus. With a time lag of 2 years the bacterial production recovered after an initial decline, further synergistically elevating the microbial heterotrophy. Current climate change projections suggesting increased precipitation may therefore lead to increased microbial heterotrophy, thereby decreasing the transfer efficiency of biomass to higher trophic levels. This prognosis would suggest reduced fish production and lower sedimentation rates of phytoplankton, a factor of detriment to benthic fauna. Our findings show that discharge of freshwater and total organic carbon significantly contributes to the balance of coastal processes at large spatial and temporal scales, and that model's would be greatly augmented by the inclusion of these environmental drivers as regulators of coastal productivity.


Experiments on rats (both in vivo and in vitro) were made to examine phospholipid transport between liver microsomes and mitochondria, microsomes and high density lipoproteins of the blood, as well as to assess the effect of nutrition on the processes under consideration. Phospholipid transport from liver microsomes to blood high density lipids under the in-vitro conditions is effected without special intermediaries. Supplementation of the incubation medium with lipid-carrying proteins from the liver speeds up phospholipid transport to blood lipoproteins. In this case, bilateral exchange of phospholipids takes place. The diets that are imbalanced as regards the content of carbohydrates and fat alter the intensity of phospholipid transport between liver microsomes and mitochondria. Phospholipid transport from cell membranes to high density proteins of the blood does not seem likely to depend on the alimentary factor.


The expression of tumor necrosis factor-alpha (TNF-alpha) mRNA in murine inflammatory peritoneal macrophages (M phi) was studied with a sensitive liquid hybridization method. Upon exposure to 10-1000 ng/ml of lipopolysaccharide (LPS), M phi were induced to express TNF-alpha mRNA in a dose-dependent manner. mRNA was detectable within 1 h after stimulation, peaked at about 2 h and then gradually declined. A 10 min treatment with LPS was enough to stimulate the maximal level of TNF-alpha mRNA, as determined in a 2 h period. Although calcium ionophore A23187 and macrophage activating factor (MAF) (both can activate M phi to mediate tumoricidal activity) did not induce TNF-alpha mRNA expression by themselves, they did act synergistically with LPS. Treatment of M phi with retinoic acid strongly inhibited LPS-induced TNF-alpha mRNA expression, whereas trifluoperazine had an opposite effect. Cycloheximide not only synergized with LPS but also induced TNF-alpha mRNA expression by itself. In contrast, actinomycin D completely blocked LPS-induced TNF-alpha gene activation. These findings indicate that LPS-induced TNF-alpha mRNA expression is not solely due to an increase in intracellular free calcium ion and is independent of the protein kinase C pathway of signal transduction. In addition, TNF gene activity may be regulated by short-lived protein repressor(s).


A 2-loop waste heat recovery system with Rankine steam cycles for the improvement of fuel efficiency of gasoline vehicles has been investigated. A high temperature loop is used to recover waste heat from exhaust gas and a low temperature loop is used to recover waste heat from cold engine coolant. In this paper has dealt with a layout of low temperature loop system, the review of the factors through numerical analysis. According to the result of analysis, the designed heat exchanger, LT Boiler has low equivalent stress than ultimate stress of the material. And comparing with flow analysis results, LT Boiler is safe to operation.


The effects of inclusion in the diet of different sources of soya bean meal (SBM) on growth performance, total tract apparent digestibility (TTAD) and apparent ileal digestibility (AID) of major dietary components and mucosal ileum morphology were studied in Iberian pigs weaned at 30 days of age. From 30 to 51 days of age (phase I), there was a control diet based on regular soya bean meal (R-SBM; 44% CP) of Argentina (ARG) origin and five extra diets in which a high-protein soya bean meal (HP-SBM; 49% CP) of the USA or ARG origin, either ground (990 μm) or micronized (60 μm), or a soya protein concentrate (SPC; 65% CP) substituted the R-SBM. From 51 to 61 days of age (phase II), all pigs were fed a common commercial diet in mash form. The following pre-planned orthogonal contrasts were conducted: (1) R-SBM v. all the other diets, (2) SPC v. all the HP-SBM diets, (3) micronized HP-SBM v. ground HP-SBM, (4) HP-SBM of ARG origin v. HP-SBM of US origin and (5) interaction between source and the degree of grinding of the HP-SBM. Dietary treatment did not affect growth performance of the pigs at any age but from 30 to 51 days of age, post weaning diarrhoea (PWD) was higher (P<0.001) and the TTAD and AID of all nutrients were lower for pigs fed the R-SBM diet than for pigs fed the HP-SBM or the SPC diets. However, no differences between the HP-SBM and the SPC containing diets were detected for any trait. The TTAD of organic matter (P=0.07) and gross energy (GE) (P=0.05) tended to be higher for the micronized HP-SBM than for the ground HP-SBM and that of GE was higher (P<0.05) for US meal than for the ARG meal. Pigs fed R-SBM had lower villus height (P<0.01) than pigs fed HP-SBM or SPC but no differences in ileal mucosal morphology were detected between SPC and HP-SBM containing diets. It is concluded that feeding the HP-SBM or SPC-reduced PWD and improved nutrient digestibility and ileal morphology as compared with feeding the R-SBM, but had no effect on pig performance. The inclusion in the diet of added value soya products (micronized SBM or SPC) in substitution of the R-SBM increased the TTAD of all nutrients and reduced PWD but had no advantage in terms of growth performance over the use of ground HP-SBM.


AbstractBACKGROUND: The growth of managed care has raised a number of concerns about patient and physician satisfaction. An association between physicians' professional satisfaction and the satisfaction of their patients could suggest new types of organizational interventions to improve the satisfaction of both.
 OBJECTIVE: To examine the relation between the satisfaction of general internists and their patients.
 DESIGN: Cross-sectional surveys of patients and physicians.
 SETTING: Eleven academically affiliated general internal medicine practices in the greater-Boston area.
 PARTICIPANTS: A random sample of English-speaking and Spanish-speaking patients (n=2,620) with at least one visit to their physician (n=166) during the preceding year.
 MEASUREMENTS: Patients' overall satisfaction with their health care, and their satisfaction with their most recent physician visit.
 MAIN RESULTS: After adjustment, the patients of physicians who rated themselves to be very or extremely satisfied with their work had higher scores for overall satisfaction with their health care (regression coefficient 2.10; 95% confidence interval 0.73–3.48), and for satisfaction with their most recent physician visit (regression coefficient 1.23; 95% confidence interval 0.26–2.21). In addition, younger patients, those with better overall health status, and those cared for by a physician who worked part-time were significantly more likely to report better satisfaction with both measures. Minority patients and those with managed care insurance also reported lower overal satisfaction.
 CONCLUSIONS: The patients of physicians who have higher professional satisfaction may themselves be more satisfied with their care. Further research will need to consider factors that may mediate the relation between patient and physician satisfaction.


The deformation mechanisms and mechanical properties of Cu/Fe multilayer during compression process are investigated via atomistic simulations and rationalized analysis. It is found that yield stress and strain of Kurdjumov–Sachs model are lower than that of Nishiyama–Wassermann model, and lattice dislocation nucleates from periodic arrangement structures on the interface. We present that preferred slip systems are dominated not only by Schmidt factors but also by intersection line orientations of slip system on the interface, as well as angles between activated slip system of Cu layer and slip system of Fe layer. During deformation process, extended full dislocation dominates deformation behavior of Cu layer, and perfect dislocation and twinning dominate deformation behavior of Fe layer. After deformation, tetrahedral structures and point defects form on Cu side of interface and inside Fe layer, respectively. We calculate evolution curves for number of dislocation segments and interface thickness to illuminate deformation behavior.


Introduction Recent systematic review confirms the potential of biomarkers to predict preterm labour.1 Aims To identify plasma biomarkers that predict preterm/term labour. Methods 82 women with threatened preterm labour (23–35/40) were recruited. Plasma was taken at presentation and repeated ≤24 h following spontaneous delivery. 10 case-matched sets of women were analysed across 2 experiments (n = 30). Each set comprised of a standardised control, asymptomatic low-risk antenatal sample, antenatal and postnatal sample from a symptomatic woman delivering at term, and antenatal and postnatal sample from a symptomatic woman delivering preterm. The Orbitrap Mass Spectrometer analysed samples. Protein changes were observed through the comparison of pre/post delivery ratios. Results Two proteins were significantly up-regulated postnatally in every term sample: Haptoglobulin, Pappalysin-1 (p < 0.05). This effect was absent in preterm groups. 5 proteins were significantly down-regulated in postnatal preterm samples, whilst up-regulated postnatally in term women; Alpha-2 macroglobulin, Ig kappa chain V-I region Lay, Ig kappa chain V-I region BAN, Corticosteroid-binding globulin, Cysteine-rich secretory protein 3 (p < 0.05). Alpha-2 macroglobulin was significantly up-regulated antenatally in a comparison of preterm women versus gestation-matched low-risk asymptomatic women (p < 0.05). Volcanic plots demonstrate that most proteins did not alter significantly (p > 0.05). Conclusion Exclusive up-regulation of 2 proteins in term deliveries suggests potential variation in the underlying mechanisms of term versus preterm labour. Nevertheless, the majority of protein changes across mid-gestation are small. The significant up-regulation of Alpha-2 macroglobulin antenatally, represents a potential plasma biomarker of clinical use for the accurate diagnosis of preterm labour.


Background Coaching psychology is of increasing interest to medical educators for its potential benefits as a facilitative method in problem-based learning (PBL). However, the field lacks empirical studies that explore the lived experiences of students and tutors in the PBL coaching process. This study aimed to elicit knowledge regarding medical students' and tutors' experiences and perceptions of PBL coaching in the context of Chinese undergraduate medical education. Methods The qualitative methodology of interpretative phenomenological analysis (IPA) was employed. Participants comprised third year medical students (n=20) and PBL tutors (n=5) who have adopted a coaching approach in PBL for a semester. Semi-structured interviews were utilized to obtain a comprehensive understanding of their experiences of PBL coaching. Data analysis followed an iterative four-stage scheme of Biggerstaff and Thompson. Results Six main themes emerged from diverse experiences and interpretations: 1) mindsets of coaching and learning, 2) the development of learning dispositions and capacities, 3) student group collaboration, 4) tutor-student relationships, 5) personal and professional development, and 6) challenges and difficulties in implementation. Conclusions It could be concluded that PBL coaching is a dynamic, facilitative process that makes a particular contribution to the learning process from psychological, emotional, and social perspectives, whilst it demonstrates significant overlaps with PBL tutoring in terms of supporting students' cognitive activities in PBL. Further research is needed to identify the barriers and challenges for medical educators to implement coaching in the PBL process.


Stormwater run-off generally refers to pluvial, i.e. rainfall related, water that does not soak into the ground at the point at which it falls. The volume and timing of stormwater run-off, specifically from roof tops is highly important to urban flood control and its capture has the potential for non-potable uses within (e.g. for WC flushing and for washing machines) and outside the home (e.g. car washing and garden watering). The former runs a risk of flash floods where local and downstream stormwater (or combined sewer) systems become overburdened in times of extreme rainfall events. The later will influence potential future urban water supplies, which is particularly important at time(s) where mains water availability is scarce (e.g. times of drought or when the national demand for water in the UK increases beyond supply capabilities) population. Rainwater harvesting (RWH) systems can benefit flood risk and water supply however their ability to do either / both is dependent on the subtleties of filling and emptying (i.e. stored water volume or spare storage capacity) which are not fully understood, particularly in peak flow events. Through the use of five years worth of daily rainfall data for Birmingham (2007 - a record breaking year for UK flooding, to 2011) these subtleties are investigated through a sensitivity type analysis of tank size, occupancy rates and technology efficiency. The results show that RWH tanks sized according to BS8515 would not have been capable of capturing rainfall that fell in peak flow events. Moreover not all yearly non-potable demands would have been met. If tanks were over-sized by a factor of 3.0 (i.e. use the larger of 15% yearly non-potable demands or rainfall) this would have been sufficient to meet all demands and eliminate roof-top run-off.


In this article, the authors develop a market risk model for hedge fund portfolios by integrating cluster analysis, extreme value theory (EVT), and copula modeling. Because the cluster model is exclusively based on fund returns, cluster classifications are more objective than self-reported styles. The EVT contribution considers the fat-tailed distribution of hedge fund returns, implicitly accounting for jump risk. The copula method accounts for the dependence between clusters. Two Gumbel copulas are constructed—one on the average returns of funds in the clusters, and the other on returns of all funds in the clusters. The first copula is directly applicable to a highly diversified portfolio and the authors show how to apply this copula to a general hedge fund portfolio. The second copula is suitable for simulations on nondiversified portfolios and also provides a tool for stress tests. Monte Carlo simulations indicate that investing in a broadly diversified hedge fund portfolio is not riskier than investing in a traditional diversified portfolio.


Oral and intravenous glucose tolerance tests were performed in ten normal subjects. Phenformin pretreatment flattened the glucose and insulin response to oral glucose loading but did not significantly alter the response to intravenous glucose. It is suggested that these results can best be explained by an inhibitory effect of the drug on the rate of intestinal glucose absorption.


It has been known for quite a while that the Vapnik-Chervonenkis dimension (VC-dimension) of a feedforward neural net with linear threshold gates is at most O(w log w), where w is the total number of weights in the neural net. We show in this paper that this bound is in fact asymptotically optimal. More precisely, we exhibit for any depth d 3 a large class of feedforward neural nets of depth d with w weights that have VC-dimension (w log w). This lower bound holds even if the inputs are restricted to Boolean values. The proof of this result relies on a new method that allows us to encode more program-bits in the weights of a neural net than previously thought possible.


BACKGROUND
 Mobile apps provide an accessible way to test new health-related methodologies. Tobacco is still the primary preventable cause of death in industrialized countries, constituting an important public health issue. New technologies provide novel opportunities that are effective in the cessation of smoking tobacco.

 OBJECTIVE
 This paper aims to evaluate the efficacy and usage of a mobile app for assisting adult smokers to quit smoking.

 METHODS
 We conducted a cluster randomized clinical trial. We included smokers older than 18 years who were motivated to stop smoking and used a mobile phone compatible with our mobile app. We carried out follow-up visits at 15, 30, and 45 days, and at 2, 3, 6, and 12 months. Participants of the intervention group had access to the Tobbstop mobile app designed by the research team. The primary outcomes were continuous smoking abstinence at 3 and 12 months.

 RESULTS
 A total of 773 participants were included in the trial, of which 602 (77.9%) began the study on their D-Day. Of participants in the intervention group, 34.15% (97/284) did not use the app. The continuous abstention level was significantly larger in the intervention group participants who used the app than in those who did not use the app at both 3 months (72/187, 38.5% vs 13/97, 13.4%; P<.001) and 12 months (39/187, 20.9% vs 8/97, 8.25%; P=.01). Participants in the intervention group who used the app regularly and correctly had a higher probability of not being smokers at 12 months (OR 7.20, 95% CI 2.14-24.20; P=.001) than the participants of the CG.

 CONCLUSIONS
 Regular use of an app for smoking cessation is effective in comparison with standard clinical practice.

 CLINICALTRIAL
 Clinicaltrials.gov NCT01734421; https://clinicaltrials.gov/ct2/show/NCT01734421


Prospective reimbursement is forcing laboratories across the country to reduce their expenditures. Following are an analysis of the direct and indirect costs in the laboratory and mathematical equations that can be used for predicting them.


Significance Although Americans believe the confusion caused by false news is extensive, relatively few indicate having seen or shared it—a discrepancy suggesting that members of the public may not only have a hard time identifying false news but fail to recognize their own deficiencies at doing so. If people incorrectly see themselves as highly skilled at identifying false news, they may unwittingly participate in its circulation. In this large-scale study, we show that not only is overconfidence extensive, but it is also linked to both self-reported and behavioral measures of false news website visits, engagement, and belief. Our results suggest that overconfidence may be a crucial factor for explaining how false and low-quality information spreads via social media. We examine the role of overconfidence in news judgment using two large nationally representative survey samples. First, we show that three in four Americans overestimate their relative ability to distinguish between legitimate and false news headlines; respondents place themselves 22 percentiles higher than warranted on average. This overconfidence is, in turn, correlated with consequential differences in real-world beliefs and behavior. We show that overconfident individuals are more likely to visit untrustworthy websites in behavioral data; to fail to successfully distinguish between true and false claims about current events in survey questions; and to report greater willingness to like or share false content on social media, especially when it is politically congenial. In all, these results paint a worrying picture: The individuals who are least equipped to identify false news content are also the least aware of their own limitations and, therefore, more susceptible to believing it and spreading it further.


Immigrants are increasingly important in driving growth and innovation in America, as evidenced by the role played by foreign-born founders and key personnel in the nation's breakthrough companies. Immigrants have started nearly half of America's 50 top venture-funded companies and are key members of management or product development teams in more than 75 percent of our country's leading cutting-edge companies. The research finds that among the top venture-backed companies, immigrant founders have created an average of approximately 150 jobs per company in the United States. The research involved conducting interviews and gathering information on the top 50 venture-funded companies in the United States, which were ranked in 2011 by the research firm VentureSource based on factors that included company growth, (successful) track record of CEOs, founders and investors, and capital raised. The companies, all privately-held and with the potential to become publicly traded on the stock market in the years ahead, are today each valued at less than $1 billion and have received venture capital (equity) financing within the past three years, an important indicator of the promise seen by investors.The research finds that 48 percent, or 24 out of 50, of the country's top venture-funded companies had at least one immigrant founder. This illustrates the increasing importance and contributions of immigrants to the U.S. economy. A 2006 study conducted with the National Venture Capital Association identified an immigrant founder in 1 in 4, or 25 percent, of publicly traded venture-backed companies created between 1990 and 2005. This study is the first to examine the role immigrants play on the management or product development team in leading private companies in information technology, health, energy, business and financial services, and other fields. The research found 38 of the top 50 companies, or 76 percent, had at least one immigrant helping the company grow and innovate by filling a key management or product development position. Chief technology officer, CEO and vice president of engineering are the most common positions held by immigrants in the top 50 venture-backed companies.


To effectively test the signal integrity problems on high-speed ultra-width buses, a test scheduling strategy which is based on the k-line dividing theory and the Wheel Rotation algorithm is proposed in this paper. With k-line dividing theory, the ultra-width bus could be divided into many sub-buses consisting of k lines each. By testing all the k-line sub-buses in parallel with Wheel Rotation algorithm, the number of test patterns required for testing the crosstalk faults on high-speed ultra-width buses can be greatly reduced. Experimental results show that the proposed approach can significantly reduce the test time while retaining the test accuracy.


Abstract. Wildfires represent a major source for aerosols impacting atmospheric radiation, atmospheric chemistry and cloud micro-physical properties. Previous case studies indicated that the height of the aerosol–radiation interaction may crucially affect atmospheric radiation, but the sensitivity to emission heights has been examined with only a few models and is still uncertain. In this study we use the general circulation model ECHAM6 extended by the aerosol module HAM2 to investigate the impact of wildfire emission heights on atmospheric long-range transport, black carbon (BC) concentrations and atmospheric radiation. We simulate the wildfire aerosol release using either various versions of a semi-empirical plume height parametrization or prescribed standard emission heights in ECHAM6-HAM2. Extreme scenarios of near-surface or free-tropospheric-only injections provide lower and upper constraints on the emission height climate impact. We find relative changes in mean global atmospheric BC burden of up to 7.9±4.4 % caused by average changes in emission heights of 1.5–3.5 km. Regionally, changes in BC burden exceed 30–40 % in the major biomass burning regions. The model evaluation of aerosol optical thickness (AOT) against Moderate Resolution Imaging Spectroradiometer (MODIS), AErosol RObotic NETwork (AERONET) and Cloud–Aerosol Lidar with Orthogonal Polarization (CALIOP) observations indicates that the implementation of a plume height parametrization slightly reduces the ECHAM6-HAM2 biases regionally, but on the global scale these improvements in model performance are small. For prescribed emission release at the surface, wildfire emissions entail a total sky top-of-atmosphere (TOA) radiative forcing (RF) of −0.16±0.06 W m−2. The application of a plume height parametrization which agrees reasonably well with observations introduces a slightly stronger negative TOA RF of −0.20±0.07 W m−2. The standard ECHAM6-HAM2 model in which 25 % of the wildfire emissions are injected into the free troposphere (FT) and 75 % into the planetary boundary layer (PBL), leads to a TOA RF of −0.24±0.06 W m−2. Overall, we conclude that simple plume height parametrizations provide sufficient representations of emission heights for global climate modeling. Significant improvements in aerosol wildfire modeling likely depend on better emission inventories and aerosol process modeling rather than on improved emission height parametrizations.


PURPOSE
To decide whether the transitory coexpression of cone visual pigments described in the developing rat and gerbil retina is a universal feature of dichromatic mammalian species.

METHODS
The rabbit, a species widely used in eye research, was selected for the study and a search made for the presence of cones that bound more than one cone antibody during the first postnatal week. To plot the densities of individual cone types and to colocalize the two visual pigments, immunocytochemistry on retinal wholemounts and consecutive tangential sections, respectively, were used.

RESULTS
The sequence in which the visual pigments began to be expressed was the same as that observed in other mammals: first, rhodopsin; second, blue pigment; and last, green pigment. The striking increase in blue cone density numbers observed in the rat, however, did not occur in the rabbit. Instead, some days after the first blue cones appeared, the green cones also started to express their visual pigment, and this cone type soon outnumbered the blue cones. Within the limits of the immunocytochemical method, it was established that unlike the developing rat, the presence of double-labeled cones was not a character of the rabbit retina.

CONCLUSIONS
Visual pigment coexpression is an interesting phenomenon of retinal development, however, it is not the exclusive scenario of photoreceptor differentiation. Each species must be carefully studied before deciding whether its retinal cones synthesize both pigments during retinal development.


One of the best-developed carbonate successions of the Lower Permian in eastern Gondwana is the Callytharra Formation, deposited above glacially influenced sediments in a narrow elongate rift basin far from the open ocean. This formation and the underlying Carrandibby Formation provide evidence for faunal changes that accompanied the melting of the Sakmarian Gondwanan ice sheets. Diverse smaller benthic foraminifera including organic-cemented agglutinated, hyaline, and porcelaneous calcitic forms, accompany a heterozoan macrofauna (mainly bryozoans, crinoids and brachiopods). Fusulinid foraminifera and calcareous algae are absent. Seven foraminiferal assemblage zones subdivide the succession and parallel changes in associated macrofauna and lithofacies. Environmental changes determined from the succession include (1) a transition from nearshore, low-energy, low-salinity, cool waters to higher-energy, normal-marine waters supporting bryozoan, crinoidal and non-skeletal-macroalgal meadows; and (2) a transition from well-oxygenated, shallow-water, sandy substrates to deeper-water, less-oxygenated, muddy substrates. Faunal comparisons suggest that at paleolatitudes higher than 45°S, in widely separated interior basins in eastern Gondwana, a change from low-diversity, siliceous-agglutinated to high-diversity, Calcitornella -rich, foraminiferal assemblages took place during the Sakmarian. This change may have been associated with a reduction in melt-water influx into the interior basins from retreating Gondwanan ice sheets. The warming was insufficient to allow colonization of the shallow seas by fusulinids and calcareous algae, which only ranged as far south as 45°S paleolatitude.


: A class of rotaxane is created, not by encapsulating a conventional linear thread, but rather by wrapping a large cucurbit[10]uril macrocycle about a three-dimensional, cylindrical, nanosized, self-assembled supramolecular helicate as the axle. The resulting pseudo-rotaxane is readily converted into a proper interlocked rotaxane by adding branch points to the helicate strands that form the surface of the cylinder (like branches and roots on a tree trunk). The supramolecular cylinder that forms the axle is itself a member of a unique and remarkable class of helicate metallo-drugs that bind Y-shaped DNA junction structures and induce cell death. While pseudo-rotaxanation does not modify the DNA-binding properties, proper, mechanically-interlocked rotaxanation transforms the DNA-binding and biological activity of the cylinder. The ability of the cylinder to de-thread from the rotaxane (and thus to bind DNA junction structures) is controlled by the extent of branching: fully-branched cylinders are locked inside the cucurbit[10]uril macrocycle, while cylinders with incomplete branch points can de-thread from the rotaxane in response to competitor guests. The number of branch points can thus a ff ord kinetic control over the drug de-threading and release.


There has been very little research that has explored self-help groups (SHGs) in relation to self-harm. Yet, from the limited research undertaken self-harm SHGs appear to provide a valuable and much needed source of support. This study explores the perspectives of those who attend and support such groups with the aim of building a more comprehensive understanding of the role of these groups.

The research is framed within an interpretative paradigm of inquiry and guided by a qualitative case study approach. The first phase involved working with two self-harm SHGs to gain an in-depth understanding of the strengths and challenges specific to these groups. In the second phase, semi-structured interviews were undertaken with four individuals who had experience of supporting self-harm SHGs directly and/or at an organisational level to gain broader insights into the running and development of such groups.

A thematic approach to the analysis of the findings illustrated that these groups provide a safe, non-judgmental space where those who self-harm can meet, listen and talk to others who share similar experiences for mutual and reciprocal peer support. Participation in the groups was found to offer direct individual benefits and wider gains, along with external and internal challenges.

Despite a current interest in the value of peer support in mental health services, the thesis illustrates that this is largely missing for those who self-harm. Concerns about the risk of peer support for those who self-harm remains a barrier affecting the development of self-harm SHGs, which is further constrained by a privileging of an individualistic approach in mainstream services. The thesis contributes new evidence about the value of collective peer support for those who self-harm. In addition it provides a more nuanced theoretical understanding of the paradoxical meaning of 'safe space' in a SHG for those who self-harm.


This study reports an integrated microfluidic system capable of automatic extraction and analysis of mitochondrial DNA (mtDNA). Mitochondria are the energy production and metabolism centres of human and animal cells, which supply most of the energy for maintaining physiological functions and play an important role in the process of cell death. Because it lacks an effective repair system, mtDNA suffers much higher oxidative damage and usually harbours more mutations than nuclear DNA. Alterations of mtDNA have been reported to be strongly associated with mitochondrial dysfunction, mitochondria-related diseases, aging, and many important human diseases such as diabetes and cancers. Thus, an effective tool for automatic detection of mtDNA deletion is in great need. This study, therefore, proposed a microfluidic system integrating three enabling modules to perform the entire protocol for the detection of mtDNA deletion. Crucial processes which included mtDNA extraction, nucleic acid amplification, separation and detection of the target genes were automatically performed. When compared with traditional assays, the developed microfluidic system consumed fewer samples and reagents, achieved a higher mtDNA extraction rate, and could automate all the processes within a shorter period of time (150 minutes). It may provide a powerful tool for the analysis of mitochondria mutations in the near future.


A robust controller design for a synchronous reluctance drive system is presented. Based on a simplified model of the system, a robust position controller has been derived. A digital signal processor (DSP), TNO-320-C30, is used to implement the control algorithm. Furthermore, all the current, velocity, and position control loops are executed by the DSP. The system, as a result, is very flexible. Although the hardware circuit of the system is very simple, the synchronous reluctance drive system can accurately control a one-axis table. In addition, the system also has good transient response, load disturbance response, and tracking ability. Several experimental results validate the theoretical analysis.


Forkhead box class O (FOXO) proteins are transcription factors that function downstream of the PTEN tumor suppressor and directly control the expression of genes involved in apoptosis, cell cycle progression, and stress responses. In the present study, we show that FOXO1 interacts with four and a half LIM 2 (FHL2) in prostate cancer cells. This interaction occurred in the nucleus and was enhanced by lysophosphatic acid. FHL2 decreased the transcriptional activity of FOXO1 and the expression of known FOXO target genes and inhibited FOXO1-induced apoptosis. Interestingly, SIRT1, a mammalian homolog of yeast Sir2, bound to and deacetylated FOXO1 and inhibited its transcriptional activity. FHL2 enhanced the interaction of FOXO1 and SIRT1 and the deacetylation of FOXO1 by Sirtuin-1 (SIRT1). Overall, our data show that FHL2 inhibits FOXO1 activity in prostate cancer cells by promoting the deacetylation of FOXO1 by SIRT1.


We live in an era where outcomes, guidelines, and clinical trials are at the forefront of medical training. However, to care implies having an understanding of the human being and build reflective practitioners impregnated of a humanistic perspective of doctoring. Although technical knowledge and skills can be acquired through training with little reflective process, it is impossible to refine attitudes, acquire virtues, and incorporate values without reflection. Empathy, which is required for a deep understanding of the human condition, could bridge the gap between patient-centered medicine and evidence-based medicine therefore representing a profound therapeutic potential. The challenge is how to teach empathy, an important issue in medical education, hard to teach and to measure. The authors' broad experience in medical education using movies points out an innovative methodology to promote empathy because it reaches the learners' affective domain. A description of the cinematic teaching methodology is provided and an extensive list of movie scenes are included so faculty and educators can try it in their own teaching scenario.


The Fox project will use an advanced programming language to build software such as operating systems, network protocols, and distributed systems. The goals of the project are to improve the design and construction of real systems software and to further the development of advanced programming languages. We will base our work on Standard ML, a modern functional programming language that provides polymorphism, first-class functions, exception handling, garbage collection, a parameterized module system, static typing, and formal semantics. The Fox project spans a wide range of research interests, from experimental systems building to type theory, and involves several faculty members. This research was sponsored by the Air Force Systems Command and the Defense Advanced Research Projects Agency (DARPA) under Contract F19628-91-C-0128. The views and conclusions contained in this document are those of the authors and should not be interpreted as representing the official policies, either expressed or implied, of the Defense Advanced Research Projects Agency or the U.S. Government.


Sheet glass powder (SGP) used in concrete making leads to greener environment. In shops, near by Chidamba- ram many sheet glass cuttings go to waste, which are not recycled at present and usually delivered to landfills for disposal. Using SGP in concrete is an interesting possibility for economy on waste disposal sites and conservation of natural re- sources. This paper examines the possibility of using SGP as a replacement in fine aggregate for a new concrete. Natural sand was partially replaced (10%, 20%, 30%, 40% and 50%) with SGP. Compressive strength, Tensile strength (cubes and cylinders) and Flexural strength up to 180 days of age were compared with those of concrete made with natural fine aggregates. Fineness modulus, specific gravity, moisture content, water absorption, bulk density, %voids, % porosity (loose and compact) state for sand (S) and SDA were also studied. The test results indicate that it is possible to manufac- ture concrete containing Sheet glass powder (SGP) with characteristics similar to those of natural sand aggregate concrete provided that the percentage of SGP as fine aggregate is limited to 10-20%, respectively.


Each of us has a story which we can think of as a set of beliefs, hopefully consistent. We make our decisions in view of our beliefs which may be probabilistic, in the general case, but simple yes or no as in this paper. Our beliefs are our envelope just as the shell of a tortoise is its envelope. Decision theory—or single agent game theory tells us when to make the best choice in a game of us against nature. But nature has no desire to further or frustrate our efforts. Nature is mysterious but not malign. Things change when there are other agents involved. Then the best thing for us to do will depend on what they do. And they will think the same. And we predict their actions in terms of what we think their beliefs are. But how do we coordinate with others whose beliefs are different? This paper addresses the issue of working together despite different beliefs.


On of the "most taxing issues" addressed by last month's report of the Independent Inquiries into Paediatric Cardiac Services at the Royal Brompton Hospital and Harefield Hospital 1 2 was the allegation that children with Down's syndrome were discriminated against at the Royal Brompton Hospital. It was alleged (but not proved) that children were inappropriately "steered away" from surgery for heart defects because they had Down's syndrome. The report recommends that: "The Trust's policies confirm clearly that people with a disability are entitled to, and will be accorded … the same rights of access to services as those without a disability; and that consultants should take the lead in implementing policies and influencing attitudes regarding equality of access." Similarly, a guiding principle in the report's model guidance to avoid discrimination is that: "Access to services, and priority for treatment, should be determined only on the basis of clinical need." The principle of equality of access is thus equal treatment for equal need.

Equality of access is uncontroversial when there are resources to treat everyone. It would then be unfair discrimination to deny a child lifesaving surgery because she had a disability—unless one believed her disability was so severe that it was not in her interests to continue to live. Until a few years ago some doctors did believe that about Down's syndrome.3 Such a view is now roundly rejected. One of the report's major points is that prolonging treatment is in the interests of a person with Down's syndrome.

Equality of access is problematic, however, when resources are scarce. The report admits there were serious shortcomings in resources for cardiac surgery in the 1980s and early 1990s, though it is difficult to judge how relevant these were to treatment decisions. However, resource considerations are critical when …


Introduction: Missed abortion is a type of abortion in which the dead fetus is retained within the uterus. The objective of the study was to find out whether the use of one or two doses of 800 µg misoprostol alone, administered intra-vaginally, is effective and safe in termination of missed abortion up to 20 weeks of pregnancy.
Materials and Methods: This Interventional study was conducted in a tertiary care hospital, for a period of 12 months. Sample size consisted of 67 cases of missed abortion up to 20 weeks of pregnancy which was confirmed by ultrasound. These patients were given 800µg misoprostol and were followed up for successful termination of pregnancy and side effects, viz., pain, excessive bleeding, need for surgical evacuation, rupture uterus and infection. If complete abortion had not been attained by a single dose, a repeat dose of 800µg vaginal misoprostol was inserted.
Results: In the present study, 88.06% patients aborted completely after giving misoprostol alone; where as 72.9% patients requiring only single dose of misoprostol. The success rate decreased with increasing parity and number of previous abortions in patients and results were found statistically significant (p = 0.008 and 0.035 respectively). Side effects were tolerable and required only proper counseling.
Conclusion: Misoprostol alone is a safe and effective method of termination of missed abortion up to 20 weeks of gestation; and will prove to be a good alternative to surgical management.

Keywords: Missed abortion, Misoprostol, Intra-vaginally, Termination of pregnancy, 20 weeks gestation, Surgical evacuation.


Although it is known that the spectral element method (SEM) has both high accuracy and a lower computational cost when compared with finite-element or finite-difference methods, the SEM is not widely utilized in the modeling of boundary value problems in electromagnetics. This paper provides a 2-D formulation of the well-known perfectly-matched-layer approach in the context of the SEM for the frequency-domain electromagnetic problems in which dielectric scatterers are involved. The formulation is then utilized to numerically study photonic nanojets after the demonstration of SEM accuracy in an electromagnetic scattering problem. Interesting cases where unusual results are obtained from scattering dielectric cylinders are reported and discussed in this paper. On the other hand, a finite-difference time-domain method that is widely deployed for investigating photonic nanojets is found to fail in successfully capturing such resonance cases. Sharp resonances are characteristic of high-Q cavities and numerical methods with high accuracy, e.g., the SEM can provide superior performance while exploring such resonators.


Objectives: This study aimed to evaluate the COVID-19 triage results of the admissions made by patients in a certain region to the Education Family Practice Center (E-FPC) during the pandemic period. Methods: Patients aged 18 years and above, who were applied to the E-FPC between March 12 and April 30, 2020, were included in the study. Every patient had filled in a triage form. Potential cases were referred to a high-level healthcare center. Polymerase chain reaction (PCR) and chest computed tomography (CT) results of the referred patients were followed up and noted. Results: Four hundred sixty-one patients were included in the study. Twenty-seven (5.9%) patients had a fever, 219 (47.5%) patients had a cough, 34 (7.4%) patients had dyspnea, and 305 (66.2%) patients had other symptoms. Eighty-six (18.6%) of the patients were admitted to the hospital for PCR test of which 15 (17.4%) had a positive test result. Seventy-one (15.4%) patients underwent a chest CT and 25 (35.2%) of them had results compatible with COVID-19. Fever was detected in 8 (53.3%) of the patients with a positive PCR result and in 6 (8.5%) patients with a negative PCR result (p<0.001). Dyspnea was detected in 13 (52.0%) patients whose chest CT results were compatible with COVID-19 and in 5 (10.9%) patients whose chest CT results were not compatible with COVID-19 (p<0.001). Conclusion: Symptoms, CT imaging, and PCR results should be evaluated together in the diagnosis of COVID-19. Triage practices should be maintained in primary healthcare centers throughout the pandemic. ©Copyright 2022 by Anatolian Journal of Family Medicine


When ethnic minority parties are excluded from government coalitions, are group attributes such as religion related to the groups' use of political violence? We argue that extremist factions within minority groups make use of divergence in religion to mobilize support for violent action when the group is excluded from government. Thus, we posit that while religion per se is not a source of violence, extremist elements of ethnic minorities, whose religion differs from the majority, may use religious divergence to mobilize group members to perpetrate terrorism. Specifically we test the hypotheses that extremist factions of an excluded group will be more likely to carry out terrorist attacks when the group's members belong to a different religion as well as when they belong to a different denomination or sect of a religion than the majority. To test these propositions, we use data on ethnic minority party inclusion in government coalitions, ethnic minority group religion, and the Global Terrorism Database (GTD) by matching perpetrators with ethnic groups for all democracies, 1970–2004.


Existing election algorithms suffer limited scalability. This limit stems from the communication design which in turn stems from their fundamentally two-state behaviour. This paper presents a new election algorithm specifically designed to be highly scalable in broadcast networks whilst allowing any processing node to become coordinator with initially equal probability. To achieve this, careful attention has been paid to the communication design, and an additional state has been introduced. The design of the tri-state election algorithm has been motivated by the requirements analysis of a major research project to deliver robust scalable distributed applications, including load sharing, in hostile computing environments in which it is common for processing nodes to be rebooted frequently without notice. The new election algorithm is based in-part on a simple 'emergent' design. The science of emergence is of great relevance to developers of distributed applications because it describes how higher-level self-regulatory behaviour can arise from many participants following a small set of simple rules. The tri-state election algorithm is shown to have very low communication complexity in which the number of messages generated remains loosely-bounded regardless of scale for large systems; is highly scalable because nodes in the idle state do not transmit any messages; and because of its self-organising characteristics, is very stable.


Abstract Lumacaftor-ivacaftor is a combination of two small molecule therapies targeting the basic defect in cystic fibrosis (CF) at a cellular level. It is a precision medicine and its effects are specific to individuals with two copies of the p.Phe508del gene mutation. The drug combination works by restoring functioning CF transmembrane conductance regulator (CFTR) protein in cell surface membranes and was the first CFTR modulator licensed for the homozygous p.Phe508del genotype. The drug is a combination of a CFTR corrector and potentiator. Lumacaftor, the corrector, works by increasing the trafficking of CFTR proteins to the outer cell membrane. Ivacaftor, the potentiator, works by enabling the opening of what would otherwise be a dysfunctional chloride channel. In vivo lumacaftor-ivacaftor improves Phe508del-CFTR activity in airways, sweat ducts and intestine to approximately 10–20% of normal CFTR function with greater reductions in sweat chloride levels in children versus adults. Its use results in a modest improvement in lung function and a decreased rate of subsequent decline. Perhaps more importantly, those treated report increased levels of well-being and their rate of respiratory exacerbations is significantly improved. This review traces the development and use of this combination of CFTR modulators, the first licensed drug for treating the homozygous p.Phe508del CF genotype at the intracellular level by correcting the protein defect.


We show analytically as well as experimentally a photonic technique for generation of frequency-tunable microwave signals. The technique involves propagating an array of uniformly spaced optical combs with identical comb profile into a length of dispersive single-mode fiber (SMF) prior to photodetection. A new scheme that involves a supercontinuum source and a Fourier-domain programmable optical processor as a spectral filter is proposed to generate the required array of optical combs. For an initial optical comb with a fixed repetition rate and a given length of standard SMF, our scheme shows that by choosing appropriate values of the number of optical combs, the number of comb lines in each optical comb, as well as the frequency spacing between the adjacent optical combs, we can generate a microwave signal whose frequency can be tuned to any integer multiple of the optical comb's repetition frequency that lies within the bandwidth of the photodetector. Based on the proposed scheme, using a 2 GHz supercontinuum source as an initial optical comb, we demonstrate the generation of stable microwave signals tunable to 8, 10, and 12 GHz.