Pediatric spinal cord injury (SCI) often leads to increased nociceptive input resulting in aberrant motor output like tremor and spasticity. Acute plasticity within spinal pain and motor networks following pediatric SCI may result in long-term sensorimotor disabilities. Despite this, pediatric SCI remains poorly understood. Part of the problem lies in the paucity of detailed studies aimed at defining sensorimotor control by nociceptors during development. This review provides an overview of work that highlights afferent control of sensorimotor networks by defined nociceptors in the developing spinal cord. Here, we focus on the well established and widely used neonatal sensorimotor model called sacrocaudal afferent (SCA) pathway. Until recently, the identity of specific subclasses of nociceptive afferents in the SCA pathway controlling developing sensorimotor networks was unknown. We highlight here the use of members of the Transient Receptor Potential (TRP) ion channels and mouse genetics to identify specific subsets of nociceptive afferents in the SCA pathway. In addition, we highlight the use of mouse genetics to map sensorimotor networks during development and potential future applications. A neonatal spinal cord model of central neuropathic pain via a defined set of nociceptors is presented as a probe into potential therapeutic avenues in neonatal SCI. Finally, knowledge translation from neonatal basic research to the pediatric population in the clinic is described. In conclusion, studies in neonatal models may lead to therapeutic strategies and pharmaceuticals for chronic pain and motor dysfunction after SCI during development.


Nine new species belonging to the Porcellidiidae are described from Queensland and New South Wales, Australia. Two new genera Ravania gen. nov., and Synurus gen. nov., have been erected to accommodate three new species from Queensland, Ravania wellsi sp. nov., R. doliocauda sp. nov., and Synurus ctenocheirus sp. nov. Two other new species, Acutiramus bipunctatus sp. nov., and Kensakia australis sp. nov., are also described from Queensland. Four new species are added to the New South Wales list, Kushia spathoides sp. nov., Acutiramus edenensis sp. nov., A. cumulus sp. nov., and A. iwasakii sp. nov. A Japanese species, Clavigofera pacifica, is recorded from NSW. This brings the total number of species known for the East coast of Australia to 30. The importance of the male antennule in taxonomy of the family is discussed.


Cities rather than individual pioneers have been the driving force in the settlement and economic development of the western half of North America. Throughout the seventeenth, eighteenth, and nineteenth centuries, western urban centers served as starting points for conquest and settlement. As these frontier cities matured into metropolitan centers, they grew from imitators of eastern culture and outposts of eastern capital into independent sources of economic, cultural, and intellectual change.From the Gulf of Alaska to the Mississippi River and from the binational metropolis of San Diego-Tijuana to the Prairie Province capitals of Canada, Carl Abbott explores the complex urban history of western Canada and the United States. The evolution of western cities from stations for exploration and military occupation to contemporary entry points for migration and components of a global economy reminds us that it is cities that "won the West." And today, as cultural change increasingly moves from west to east, Abbott argues that the urban West represents a new center from which emerging patterns of behavior and changing customs will help to shape North America in the twenty-first century.


The Michael addition of benzylamine to the homochiral methylenebutanedioate 10 gave an adduct 11 in good yield with high stereoselectivity. By performing the reaction in methanol the (2R,3R) diastereoisomer 11 was obtained in 88% de, which was increased to 98% de after recrystallisation of the primary amine derivative 13. The ratio of diastereoisomers was reversed by performing the reaction in aprotic solvents, with the (2R,3S) diastereoisomer 12 being obtained in 40% de in tetrahydrofuran. The Michael adduct 11 is formed under kinetic control. The primary amine 15 is a key intermediate in the synthesis of novel matrix metalloproteinase inhibitors.


I. INTRODUCTION The people of North Carolina have the power to elect the justices who sit on the state's Supreme Court. (1) Between 1995 and 2002, the registered voters of the state used this power to transform the court from one dominated by Democrats to one controlled by Republicans. (2) From 1995 to 1998, the court was composed of five Democrats and two Republicans. (3) The election of Republicans Mark Martin and George L. Wainwright, Jr. in 1999, both taking seats formerly held by Democrats, marked the beginning of the change. (4) In 2000, Republicans I. Beverly Lake, Jr. and Robert H. Edmunds, Jr. won their races, further shifting the balance of the court, and leaving only two Democrats still holding seats. (5) The 2003 election ushered in another Republican justice--Edward Thomas Brady--and created a court comprised of six Republicans and one Democrat. (6) This high court study of the North Carolina Supreme Court was conducted in order to determine what impact, if any, this dramatic shift in the court's political composition had on its rulings in both criminal and tort cases. Did the court's voting pattern fluctuate as a result of the changes in the number of Democratic or Republican justices? And if so, would it be possible to judge a court simply based on the party affiliations of its members? This study addresses these questions. In order to gain insight into the effect recent changes have had on the court, one must go beyond the partisan labels of the justices and examine each justice's voting record and individual writings to discern the true nature of each one's decision-making process. (7) This study was designed to explore these issues and provide a comprehensive analysis of the North Carolina Supreme Court. Part II describes the methodology used to conduct this study. It will also expand on what is meant by "conservative" and "liberal" in the judicial sense, labels that will be used to provide a general idea of each justice's judicial approach. Part III briefly discusses the court's organizational structure and the justices who were included in the study. Parts IV and V examine and analyze each justice's voting record along with his or her judicial values and philosophies. Part VI assesses the court as a whole and concludes that during the eight-year period considered, the court remained conservative when voting on criminal cases, but became more liberal in its treatment of tort cases. II. THE STUDY The methodological process of this study involved analyzing both criminal and tort cases decided by the North Carolina Supreme Court that resulted in divided opinions. (8) Criminal cases were examined separately from tort cases in order to determine whether a particular justice's voting tendency would remain consistent regardless of the subject matter. Only cases filed between 1995 and 2002 were included in this study. By utilizing a two-part analysis, a broad and in-depth understanding of each justice's decision-making process emerged. The first part of the analysis was quantitative in nature, providing a general picture of each justice's conservative or liberal leanings. This study reviewed forty-two criminal cases; in each case a justice's vote was labeled either pro-defendant or pro-prosecution. A vote was classified as "pro-defendant" if it operated to protect the rights of the accused: conversely, a justice's vote was classified as "pro-prosecution" if it favored an outcome the state desired or advocated. This study also analyzed thirty tort cases; for each case, a justice's vote was labeled as either pro-individual or pro-tortfeasor. A vote was labeled "pro-individual" if the reasoning used to support the vote protected the rights of an allegedly injured party. If the vote protected the alleged tortfeasor, to the detriment of the allegedly injured party, it was deemed to be a "pro-tortfeasor" vote. Graphing the pro-defendant and pro-individual voting percentages demonstrated the voting tendencies of each justice, and the court as a whole. …


Over the recent years, mobility in wireless communications has become a big
interest of communication and network researches due to the rising demand on
and expectations of wireless Internet access. However, since none of the existing
wireless technologies can individually fulfill all the tasks arising from the
Internet users' demands, the integration or coexistence of different
communication systems having different network characteristics is inevitable.
This integration on the other hand, requires seamless inter-system mobility
solutions. Every inter-system roaming which leads to vertical handoff requires
proper interaction of both link and IP layers, since network point of attachment
as well as the device interface are involved in handoff. Many investigations in standardization are being made to finally design and implement each of these
communication layers. This thesis details out the whole research, which is done
in two main components. As for the first component, a link layer mechanism
with the notion of a selection algorithm based on weighted mean is primarily
introduced for collecting link layer information and discovering the candidate
access router. This mechanism is then used as handoff decision phase with an
improved mobile-assisted handoff method as an extension of Fast Mobile IPv6
Handoff (FMIPv6) in vertical mode. The performance of the proposed methods
is discussed using analysis and comparison of simulation results with wellknown
methods in the field. The method has been shown to achieve
performance improvements in terms of higher preference level of selection for
various cases, and in terms of latency and packet loss, by 45% and 83%
respectively, while maintaining comparatively lower buffer sizes. As the second
component, a framework is proposed to incorporate an integration mode of
cellular and wireless networks called semi tightly-coupled. This framework is
further used to design and implement an end-to-end roaming solution as
Vertical Fast Handoff (VFHO) for the integrated network. The performance of
the proposed framework has been analyzed mathematically and through
simulations which show the robustness of VFHO in terms of signaling cost, endto-
end packet delivery cost, overall handoff latency, and packet loss based on
various system variables. Under several simulations, the number of lost packets
encountered by VFHO stayed as low as 20 packets when the arrival rate was a maximum of 50 packets per second, and did not exceed 10 packets in the case
when packet sizes was at a maximum of 256 Bytes or when buffer size was set to
50 KB. Besides, the delay varied between 200 and 600 ms in cases when the
Duplicate Address Detection (DAD) and wireless link delays reached up to 600
ms and 70 ms, respectively. In conclusion, the selection-based decision
mechanism in vertical handoff such as VFHO, can be good for congestion
control, and achieve long-term objectives such as load sharing.


Objective A systematic summary of the observational studies informing heart transplant guideline recommendations for selection of candidates and donors has thus far been unavailable. We performed a meta-analysis to better understand the impact of such known risk factors. Methods We systematically searched and meta-analysed the association between known pretransplant factor and 1-year mortality identified by multivariable regression models. Our review used the Grading of Recommendations, Assessment, Development and Evaluation for assessing the quality of assessment. We pooled risk estimates by using random effects models. Results Recipient variables including age (HR 1.16 per 10-year increase, 95% CI 1.10–1.22, high quality), congenital aetiology (HR 2.35, 95% CI 1.62 to 3.41, moderate quality), diabetes (HR 1.37, 95% CI 1.15 to 1.62, high quality), creatinine (HR 1.11 per 1 mg/dL increase, 95% CI 1.06 to 1.16, high quality), mechanical ventilation (HR 2.46, 95% CI 1.48 to 4.09, low quality) and short-term mechanical circulatory support (MCS) (HR 2.47, 95% CI 1.04 to 5.87, low quality) were significantly associated with 1-year mortality. Donor age (HR 1.20 per 10-year increase, 95% CI 1.14 to 1.26, high quality) and female donor to male recipient sex mismatch (HR 1.38, 95% CI 1.06 to 1.80, high quality) were significantly associated with 1-year mortality. None of the operative factors proved significant predictors. Conclusion High-quality and moderate-quality evidence demonstrates that recipient age, congenital aetiology, creatinine, pulsatile MCS, donor age and female donor to male recipient sex mismatch are associated with 1-year mortality post heart transplant. The results of this study should inform future guideline and predictive model development.


The recent decision of the High Court in Cameron v The Queen provides a timely opportunity to re-examine the precise rationales behind the policy observed in all Australian criminal courts (whether exercising State or Commonwealth jurisdiction) of 'discounting' an otherwise appropriate sentence in return for a plea of guilty. It also raises important issues regarding the appropriateness of 'utilitarianism' as one of those rationales, the relevance, as a sentencing factor, of the timing of a guilty plea, and the desirability of the sentencing court placing on the record what level of discount has been granted, and on what basis. Controversially, it raises the prospect of future High Court rulings to the effect that a discount for pleading guilty is discriminatory of those who exercise their right to plead not guilty, thereby obliging the Crown to prove its allegations against them. Finally, it reminds us yet again of the fragility of the current regime for providing indigent accused with adequate legal representation.


This manuscript deals in confirmation of drop in photovoltaic panel temperature under load. Two panels are compared, one with the load and other without the load. The panel under load should have larger heat dissipation (i.e. be cooler), when electrical yield is taken as an outgoing heat flow. During the experiment, a thermovision of the panels under solar irradiance was made with the thermal camera. Results of the first case show only minor change in panel temperature. Results of the second case, where one panel is under load, show reduced temperature of loaded panel, by up to 4 °C. Previously developed numerical model is updated with the measured data in the experiment. A measured electrical yield is taken into the account when the solar irradiance was modelled. Numerical model confirms the temperature drop and corresponds with infrared thermography data. Gained results can help in design of the photovoltaic systems, where more variants of operating conditions can be used in order to keep the panel on desired operating temperature.


In 1995, one of the largest outbreaks of human toxoplasmosis occurred in the Pacific Northwest region of North America. Genetic typing identified a novel Toxoplasma gondii strain linked to the outbreak, in which a wide spectrum of human disease was observed. For this globally-distributed, water-borne zoonosis, strain type is one variable influencing disease, but the inability of strain type to consistently explain variations in disease severity suggests that parasite genotype alone does not determine the outcome of infection. We investigated polyparasitism (infection with multiple parasite species) as a modulator of disease severity by examining the association of concomitant infection of T. gondii and the related parasite Sarcocystis neurona with protozoal disease in wild marine mammals from the Pacific Northwest. These hosts ostensibly serve as sentinels for the detection of terrestrial parasites implicated in water-borne epidemics of humans and wildlife in this endemic region. Marine mammals (151 stranded and 10 healthy individuals) sampled over 6 years were assessed for protozoal infection using multi-locus PCR-DNA sequencing directly from host tissues. Genetic analyses uncovered a high prevalence and diversity of protozoa, with 147/161 (91%) of our sampled population infected. From 2004 to 2009, the relative frequency of S. neurona infections increased dramatically, surpassing that of T. gondii. The majority of T. gondii infections were by genotypes bearing Type I lineage alleles, though strain genotype was not associated with disease severity. Significantly, polyparasitism with S. neurona and T. gondii was common (42%) and was associated with higher mortality and more severe protozoal encephalitis. Our finding of widespread polyparasitism among marine mammals indicates pervasive contamination of waterways by zoonotic agents. Furthermore, the significant association of concomitant infection with mortality and protozoal encephalitis identifies polyparasitism as an important factor contributing to disease severity in marine mammals.


Schizophrenia is a severe mental health condition that requires a long and complicated diagnostic process. However, early diagnosis is vital to control symptoms. Deep learning has recently become a popular way to analyse and interpret medical data. Past attempts to use deep learning for schizophrenia diagnosis from brain-imaging data have shown promise but suffer from a large training-application gap - it is difficult to apply lab research to the real world. We propose to reduce this training-application gap by focusing on readily accessible data. We collect a data set of psychiatric observations of patients based on DSM-5 criteria. Because similar data is already recorded in all mental health clinics that diagnose schizophrenia using DSM-5, our method could be easily integrated into current processes as a tool to assist clinicians, whilst abiding by formal diagnostic criteria. To facilitate real-world usage of our system, we show that it is interpretable and robust. Understanding how a machine learning tool reaches its diagnosis is essential to allow clinicians to trust that diagnosis. To interpret the framework, we fuse two complementary attention mechanisms, 'squeeze and excitation' and 'self-attention', to determine global attribute importance and attribute interactivity, respectively. The model uses these importance scores to make decisions. This allows clinicians to understand how a diagnosis was reached, improving trust in the model. Because machine learning models often struggle to generalise to data from different sources, we perform experiments with augmented test data to evaluate the model's applicability to the real world. We find that our model is more robust to perturbations, and should therefore perform better in a clinical setting. It achieves 98% accuracy with 10-fold cross-validation.


Until recently love existed in the realm of poets, artists and philosophers. Latterly it has been studies from multiple scientific perspectives. The author argues that the specialist approach has overlooked the importance of love as a potential new strategy for human survival, and that the old survival strategy, the domination of nature and other human groups, is no longer appropriate. By weaving together data from a multitude of disciplines, Michel Odent is able to back up his argument in insightful and exciting ways, making the case for the adoption of radical new strategies for human survival. This revised edition includes two new chapters. Michel Odent is the author of The Farmer and the Obstetrician, also published by Free Association Books and and is more familiarly known as the obstetrician who introduced new birthing concepts which played a significant part in the radical change in attitudes towards maternity and childbirth in recent years. The author of 10 books in 19 languages, Dr Odent continues his research at the Primal Health Centre in London, which he founded.


This article focuses on the development of a language portfolio for teachers in primaty education. Portfolios are being used more and more in education, particularly in higher education. But also in primary education, a language portfolio for pupils (which has been accredited by the European Council) has been introduced and turned out to be useful, especially in schools with a multicultural population. Following the same guidelines as in the pupil's portfolio, a language portfolio for teachers has been developed. The first version of this portfolio has been used in a small-scale evaluation. It turned out that the language portfolio for teachers can function as an instrument for the evaluation and documentation of the language, didactic and cultural knowledge, and skills of teachers. Teachers can use the portfolio to assess their own proficiencies and to collect and store documentation of their proficiencies. Major differences were foundin the views of language teachers in primary schools (teachers of Turkish and Arabic) and those of general teachers. The latter group expressed their doubts about the usefulness of the language portfolio in their teaching situation, as teaching language (meaning: teaching English) is only a small part of their task. Recent developments in primary education, however, seem to point to a growing importance of languages in this type of education. In this case, language portfolios could prove to be useful instruments.


In May 2013, the American Psychiatric Association released the fifth edition of the Diagnostic and Statistical Manual of Mental Disorders ("DSM-5"). Among other changes, the DSM-5 includes new entries for hoarding disorder and premenstrual dysphoric disorder as well as a reclassified entry for gambling disorder. Using these changes as examples, this Article examines the implications of the DSM-5 for key issues in health law, including health insurance coverage, public and private disability benefit eligibility, and disability discrimination protection. As a descriptive matter, this Article illustrates how the addition  of new disorders and the reclassification of existing disorders in the DSM- 5 can significantly impact health insurance coverage and has some  relevance to disability benefit eligibility and disability discrimination  protection. From a normative perspective, this Article offers guidelines  designed to prevent attorneys, judges, and other nonclinicians from  abusing the DSM-5 in civil and administrative health law proceedings.


The purpose of this study was to gain initial feedback from lesbian, gay, bisexual, trans, queer, two-spirit and other gender and sexual minority (LGBTQ2S+) counsellors, social workers and anti-violence workers on the Islands of Safety response-based model and whether it could be used in LGBTQ2S+ communities. Online, asynchronous focus groups were conducted over the course of a week in February 2016 with 26 counsellors, social workers, psychiatric nurses, antiviolence workers and outreach workers from across a spectrum of genders, sexualities and ethnicities. Results showed that resistance and dignity were the most embraced response-based ideas. Focusing on both responses and impacts of violence was important. Including family of choice, using the client's language for their gender and sexuality and not making assumptions about family structure and the gender of the primary parent was important. Participants who stated that they knew about or were connected to Métis and Indigenous cultures and politics supported working to bridge differences in genders and sexualities across cultures without changing the Islands of Safety model. Non-Indigenous, non-Métis LGBTQ+ health care practitioners need more training around Métis and Indigenous views of gender and family structure to contextualize the traditional view of family used in the model. Adapting the Islands of Safety model for LGBTQ2S+ communities iv


The detection of circulating breast cancer cells in blood could be of special interest as an indicator of diagnosis and prognosis, and for the selection of treatment. In a previous report, our research group determined gene expression pro- files in samples of breast cancer tissue, identifying over-expression of the BIK/NBK mRNA gene in 90% of the analyzed samples. In this paper, we analyze the BIK/NBK gene expression as a possible biomarker of circulating breast cancer cells in blood. We demonstrate that the BIK/NBK gene expression is not a significant biomarker in the detection of circulating breast cancer cells in the blood of women with breast cancer. Several studies have evaluated the regulation of apoptosis by estrogens in breast cancer cells, demonstrating the importance of BIK/NBK protein, in estrogen-regulated breast cancer cell apoptosis, which suggests that the regulation of its expression may be an important therapeutic target or strategy in the management of cancer, and, although we did not find statistically significant differences among the patient groups to demonstrate that BIK/NBK gene expression is a biomarker of circulating breast cancer cells in blood, we consider it neces- sary to continue the study of this gene in breast cancer tissue and its role in the development and progression of breast cancer, its prognostic value, and its potential use as therapeutic target.


Most machine learning algorithms are lazy: they extract from the training set the minimum information needed to predict its labels. Unfortunately, this often leads to models that are not robust when features are removed or obscured in future test data. For example, a backprop net trained to steer a car typically learns to recognize the edges of the road, but does not learn to recognize other features such as the stripes painted on the road which could be useful when road edges disappear in tunnels or are obscured by passing trucks. The net learns the minimum necessary to steer on the training set. In contrast, human driving is remarkably robust as features become obscured. Motivated by this, we propose a framework for robust learning that biases induction to learn many different models from the same inputs. We present a meta algorithm for robust learning called FeatureBoost, and demonstrate it on several problems using backprop nets, k-nearest neighbor, and decision trees.


Deterioration processes occurring within two moving surfaces of tribological system manifested through the loss of material or any other material change are defined as wear. In this contribution, the analysis of wear is indispensable in terms of wear rate decrease as the point in time at which the system becomes nonfunctional. It is assumed that this moment in time can be postponed by ensuring lower wear rate. The technical system concerned in this contribution as example is a wind turbine system (WTS). The analysis of wear mechanisms herein is carried out taking into consideration critical components of WTS. Concerning this the most attention is attracted to thermal, mechanical, and chemical aspects of wear processes occurring in critical components and contributing to the loss of functionality due to related aging. The failures appearing within wind turbine systems as well as corresponding decrease in WTS reliability are intensively inferred in recent years. A number of reliability databases have ensued targeting to obtain detailed knowledge of failure causes and failure modes with special emphasis to the correlation of failure modes to applied loads. Using benchmark data stored in reliability databases, the identification of critical components concerning the failure occurrence frequency, the number of system downtimes, mean time between failures, as well as related additional reliability parameters is facilitated. In this contribution, the focus is given on wear process of rotor blades and bearings. The wear modes briefly introduced herein are associated with aforementioned components. The idea lies behind gaining the knowledge about actual system's state is the modeling of deterioration processes. Finally, the options for adapted operating conditions targeting to achieve decreased deterioration rate are pointed out. doi: 10.12783/SHM2015/353


This paper gives a critical review of E.A.Nida's translation theory of dynamic equivalence and initiates a comparative study of dynamic equivalence and formal correspondence with special reference to the translation between English and Chinese, for the purpose of confirming the applicability of dynamic equivalence to English-Chinese translation. The findings further prove that though the theory of dynamic equivalence has its defects, it usually takes precedence over formal correspondence in the translation between the Chinese and the English languages.


OBJECTIVE
To describe a frameless stereotactic technique used to resect cerebral arteriovenous malformations (AVMs) and to determine whether frameless stereotaxy during AVM resection could decrease operative times, minimize intraoperative blood losses, reduce postoperative complications, and improve surgical outcomes.

METHODS
Data for 44 consecutive patients with surgically resected cerebral AVMs were retrospectively reviewed. The first 22 patients underwent resection without stereotaxy (Group 1), whereas the next 22 patients underwent resection with the assistance of a frameless stereotaxy system (Group 2).

RESULTS
The patient characteristics, AVM morphological features, and percentages of preoperatively embolized cases were statistically similar for the two treatment groups. The mean operative time for Group 1 was 497 minutes, compared with 290 minutes for Group 2 (P = 0.0005). The estimated blood loss for Group 1 was 657 ml, compared with 311 ml for Group 2 (P = 0.0008). Complication rates, residual AVM incidences, and clinical outcomes were similar for the two groups.

CONCLUSION
Frameless stereotaxy allows surgeons to 1) plan the optimal trajectory to an AVM, 2) minimize the skin incision and craniotomy sizes, and 3) confirm the AVM margins and identify deep vascular components during resection. These benefits of stereotaxy were most apparent for small, deep AVMs that were not visible on the surface of the brain. Frameless stereotaxy reduces the operative time and blood loss during AVM resection.


In this study we explore the seasonal variability of the mean winds, diurnal, semidiurnal tidal amplitude and phases as well as the Reynolds stress components during 2019, utilizing meteor radars at six southern hemisphere locations ranging from midto polar latitudes. These include Tierra del Fuego, King Edward Point on South Georgia island, King Sejong Station, Rothera, Davis and McMurdo stations. The year 2019 was exceptional in the southern hemisphere, due to the occurrence of a rare minor stratospheric warming in September. Our results show a substantial longitudinal and latitudinal seasonal variability 5 of mean winds and tides pointing towards a wobbling and asymmetric polar vortex. Furthermore, the derived momentum fluxes and wind variances, utilizing a recently developed algorithm, reveal a characteristic seasonal pattern at each location included in this study. The longitudinal and latitudinal variability of vertical flux of zonal and meridional momentum is discussed in the context of polar vortex asymmetry, spatial and temporal variability, and the longitude and latitude dependence of the vertical propagation conditions of gravity waves. The horizontal momentum fluxes exhibit a rather consistent seasonal structure 10 between the stations while the wind variances indicate a clear seasonal behaviour and altitude dependence showing the largest values at higher altitudes during the hemispheric winter and two variance minima during the equinoxes. Also the hemispheric summer mesopause and the zonal wind reversal can be identified in the wind variances. Copyright statement. CC BY 4.0 License


Rheumatoid arthritis (RA) is an autoimmune disease that primarily affects thejoints and is characterized by bone and cartilage erosion. These patients have an
increased risk of developing co-morbid cardiovascular disease (CVD). In this study the vascular adventitia from patients with coexisting RA and CVD was investigated to identify factors in the vascular environment that could affect the immune component of RA. This included the histological evaluation of aortic adventitial sections for known RA-associated autoantigens; B cells their survival
factors and associated cytokines. In addition, these human studies were the impetus for the initiation of a study to investigate the effect of B cell depletion
on atherosclerosis.

Citrullinated proteins (CP), RA associated antigens, are an inflammation specific entity. These modified proteins are processed by (PADI), a calcium dependent enzyme expressed by inflammatory cells and some microbial species. The presence of RA specific autoantibodies (ACPA) suggests a role for citrullinated proteins in RA pathogenesis. The aim of the present study was to determine whether the inflammatory milieu in the vascular adventitia of RA patients had any association with CP. The expression of CP was confirmed in the vascular adventitia, and CVD patients with coexisting RA were found to have increased levels of CP compared to non-RA CVD patients. In addition, ACPA levels were detectable in serum samples of only RA patients. When ACPA positive RA patients were sub grouped (CP>5.5), a strong association was observed between ACPA levels and C-reactive protein (CRP) in this subgroup (CP>5.5). This is suggestive of a CP and ACPA link in vascular inflammation in patients with coexisting RA.
The presence of B-lymphocytes has been shown in both murine and human vascular adventitia. In this study we demonstrated that the presence of B cell aggregates is tissue specific, since matched internal mammary artery (IMA) had no detectable B cells in the adventitia. Furthermore, BAFF and APRIL are present in the aortic adventitia and support the conclusion that a survival niche is present in the aortic adventitia; cytokine expression was demonstrated in lymphocytes, adipocytes and vascular endothelial cells. Interestingly, smoking resulted in higher levels of BAFF expression in the aortic adventitia of CVD patients. Previous studies have shown that smoking induces vasoconstriction of small vessels (vasa vasorum), and hence hypoxia of the vascular endothelial cells. We hypothesised that hypoxia would induce the increased expression of BAFF and APRIL in vascular endothelial cells. Using murine vascular endothelial cells we investigated the effect of hypoxia on BAFF and APRIL mRNA transcript
levels. However, hypoxia did not have any effect on transcript levels. In addition, significant correlations were observed in RA patients only, between B
cells and APRIL, B cells and CP, APRIL and CP. This part of my thesis demonstrates that the aortic adventitia of RA patients with coronary heart disease is associated with an environment that is conducive to B cell survival and
harbours a known RA-associated self-antigen. Importantly, these insights provide a rationale for the perpetuation of B cell auto-reactivity outside of both lymphoid tissue and the joint in RA.

Previous studies have shown that atherosclerosis is a T cell mediated disease with an imbalance in Th1 and Th2 responses. Macrophages and interleukin 18 (IL-
18, proatherogenic) cytokine have been demonstrated in aortic adventitia of humans in previous studies. However, their expression in the vascular adventitia of RA patients has not been investigated. The present study confirmed
macrophage IL-18 expression in vascular adventitia, which is similar among the Subgroups (RA vs. non RA) and (smokers vs. non smokers). Furthermore, a Th2 phenotype has been proposed as atheroprotective, mediated by anti oxLDL antibody producing B cells. Interestingly, recent studies have demonstrated interleukin 33 (IL-33) a Th2 cytokine to reduce the atherosclerotic lesion in an experimental model of atherosclerosis. However, it's expression and
significance in human vessels has not been extensively investigated. In this study, using immunohistochemistry, IL-33 was localised to vascular endothelial cells of vasa vasorum in aortic adventitia and lining layer of IMA. Importantly, IL-33 was down regulated in smoker's AA suggestive of failed protective mechanism
of this Th2 cytokine. In contrast, IL-33 expression was not affected by smoking in the matched IMA tissue.
In the past B-lymphocytes have been shown as an atheroprotective pathway; whereas the use of B cells depletion therapy (Rituximab) suggests a proinflammatory role of these cells in RA. Could B cell depletion therefore
mediate unexpected deficit on vascular lesions in RA? My thesis revealed expression of B cells and their survival factors in the aortic adventitia. Therefore
to investigate the impact of B cell depletion therapy on atherosclerosis, a mouse model (huCD20/ApoE-/-) was generated. The preliminary data are suggestive of
reduction in atherosclerotic plaques with B cells depletion. These studies will be extended in future to formally test the above hypothesis.

In summary I have shown for the first time the cytokine and cellular niche that exists in human aorta in RA patients. Such data will in due course inform the mechanism of accelerated vascular pathogenesis in RA.


Framed within Antoine Culioli's Enunciative Model of language, this article suggests a new analysis regarding the semantic properties of the suffix -esque and argues that this suffix refers to an alterity expressed within a typical property. Moreover this article reassesses earlier findings made about the suffix -esque, namely its low productivity in creation of neologisms and its apparent usage limited to literary and journalistic styles. The alleged constraint for all its bases to be referring to a human being is also reconsidered and our semantic analysis questions the value of "extreme" supposedly added by -esque to the nominal basis. Indeed, its usage in French shows that if this suffix is no longer typically associated to a nominal basis referring to the people of a country (see mauresque or arabesque), the human dimension associated to the nominal basis such as in la soldatesque, is not always found either (see TV-esque). Rather, this suffix seems to have lost its role as a simple identifier towards a referential domain as found in expressions such as une oeuvre molièresque which could be glossed over as "une oeuvre typique de Molière". This identification is most of the time linked to a laudatory or negative appreciation on the part of the enunciator, as found in examples such as gargantuesque. Besides, the contemporary dynamism of the -esque flexion enables the creation of neologisms. These neologisms are derived from proper nouns (mitterrandesque) or from acronyms (rmiesque) that do not exhibit standard properties. This begs the question of whether the value which seemed to be added to the composite [noun + esque] is determined by the suffix itself or whether it is partially connected to the atypical notional value of the root's semantic value.


ABSTRACT Gelinas, M.; Bokuniewicz, H.; Rapaglia, J., and Lwiza, K.M.M., 2013. Sediment resuspension by ship wakes in the Venice Lagoon. Observations of Bernoulli wakes were recorded and analyzed for 22 passing ships in the industrial Malamocco–Marghera shipping channel in the Venice Lagoon. The wakes were characterized as a progressive N-wave with a dominant, leading trough preceded and followed by small crests. As the wake traveled, water transport under the trough was initially opposite the direction of wake propagation, sending resuspended sediment back toward the channel. Water velocities were documented to reach more than 2 m s−1 under the trough, and suspended sediment concentrations exceeded 380 mg L−1. Sediment loads were successfully predicted from measurements of current speeds, settling speeds, and sediment flux determined as a function of bottom shear stress. Resuspension rates reached several thousand milligrams per square meter per second. The size of the wake, and the amount of resuspension it can cause, might be parameterized by a nonlinear combination of a blocking coefficient S and a depth-based Froude number F; both parameters depend only on the channel geometry and ship's dimensions and speed. In this case, both the depth of the trough and the maximum suspended sediment concentration depended on S1.6F3.5.


Through the Air Quality Education in Animal Agriculture (AQEAA) project, Land-Grant University specialists from across the U.S. have been collaborating in delivering applied, research-based air quality information to those who work with livestock and poultry producers. The AQEAA project developed Air Quality content on the Animal Manure Management eXtension website in collaboration with the Livestock and Poultry Environmental Learning Center (LPELC). The Air Quality web content makes widely accessible the educational resources produced by this project for use in developing the knowledge base and skills of professionals who interact [and pre-professionals who plan to interact] with livestock and poultry producers. The online materials include 18 written publications, 3 videos, and 16 recorded webinars (webcasts). Also made accessible are selected research and technology summaries as well as online content produced by other organizations. The AQEAA project also developed the skills of professionals regarding air quality topics via professional development events. Website usage information, participant polls, and stakeholder surveys provided evidence that the resources developed by this project are being utilized and that delivery of the information via eXtension has been an effective means of communicating information on this topic. Webcasts were especially effective in communicating information and providing continuing professional development. AQEAA-sponsored workshops were effective in providing in-depth air quality information and experiences to more than 300 professionals. Collaboration with the LPELC facilitated having a ready eXtension outlet for project materials and is providing continued, sustainable access to online information from this project.


In this paper we estimate and compare several alternative exchange rate models that have received wide attention, but little comparison, during the 1970s. In order to compare purchasing power parity (PPP), nominal interest rate parity, real interest rate parity, and portfolio balance models, we first strip each down to its essential core and undertake comparable single-equation tests of both 'hard' and 'easy' (more and less constrained) versions of each model. We then embed each of the 'hard' versions in a new macroeconomic model of Canada, and assess their implications for the impacts of monetary and fiscal shocks. Using annual Canadian data from the 1950s and 1970s, all of the models have single-equation errors of about 3%, except for the 'hard' versions of PPP and real interest parity, which are heavily rejected by the data. In a macroeconomic context, the models have modestly different implications for the effects of fiscal shocks, and diverge more widely under monetary shocks.


As most of us are unaware that we have a very effective and efficient relational database with the name FileMaker which falls under the category of less known Relational Database Management System (RDBMS) to develop and deploy all types of computer applications to manage the business of a Small and Medium Enterprises (SME's). Our research paper presents a time tested computerized information system designed to manage class/department for Cihan University, Erbil. The main objective of this research paper is to offer an automated, faster and efficient system to the end-user in order to process faster and increase the overall efficiency in the overall cycle. As of now the system has been deployed for single entity i.e. teacher. Later on we would extend it to the usage of Head of the Department (HOD) & the office secretary as well. Our objective of this practical research would be to focus on the design part as well as the functionality of the application software.


In the present study reduction of nitrogen oxides using reburning technology, during combustion of sewage sludge (fuel I) and the mixture of sewage sludge, wasted bleaching earth and CaO (fuel II), was carried out. The experimental works were conducted in a laboratory-scale fluidized bed reactor (power up to 10 kW) with application of two types of beds: chemically inert bed (sand) and chemically active bed (CaO). The second combustion (reburning) zone in the reactor was formed by dosing into an area above the bed, additional gaseous fuel (propane). Obtained reduction in emissions of nitrogen oxides in both types of beds was at a level 70% - 79%. Additionally bed of CaO has the desulfurizing effect and also reduces the CO concentration in the exhaust fumes. A significant drawback of active bed is the adverse effect on increase of the primary NO which enters the second combustion zone. The result of this fact is higher NOx emission during combustion of the same fuel in bed of CaO in comparison to the combustion of this fuel in the sand bed, when the same maximum degree of reduction of NOx will be obtained for both types of beds.


Traditionally, mothers in Nova Scotia have sought out prenatal education through inperson formats. Recently, however, more online resources have become available, for example, in 2014, a free prenatal education website was introduced by Public Health to replace in-person classes. The purpose of this inquiry was to explore mothers' experiences of prenatal information and support in Nova Scotia. Semi-structured interviews were conducted with eight first-time mothers. Feminist poststructuralism and discourse analysis were used to analyze how women's experiences were socially and institutionally constructed. Results revealed that pregnancy was a significant moment in time for all participants, yet becoming a mother encompassed more than the information they received. The findings of the study suggest that nurses, researchers, and policy makers may have to reconsider the structure of maternity programs to reflect the notion that women's transition of 'becoming a mother' is a process, beginning in pregnancy and continuing into the postpartum period.


Background Paramedics are called on frequently to provide care to patients with mental health and/or and alcohol and other drug (AOD) problems, but may have mixed views about how this fits within their role. Aims To explore paramedics' experience of caring for patients with non-medical emergency-related mental health and/or AOD problems, understand their perceptions of their scope of practice in caring for these patients, and ascertain if their practice should be extended to incorporate education with these patients. Method A convenience sample of 73 paramedics from most Australian states and territories—recruited through an online survey—participated in individual audio-recorded, qualitative interviews, conducted by telephone. The interviews were part of a mixed method study comprising qualitative interviews and online survey. A Framework Method of analysis to analyse the qualitative data. Results Three themes and sub-themes were abstracted from the data about participants' experiences and, at times, opposing viewpoints about caring for patients with non-medical emergency-related mental health and/or AOD problems: caring for these patients is a routine part of paramedics' work, contrasting perspectives about scope of practice in caring for this group of patients, competing perspectives about extending scope of practice to incorporate education with this cohort of patients. Conclusions Paramedics need more undergraduate and in-service education about the care of patients with mental health and/or AOD problems, and to address concerns about extending their scope of practice to include education with these patients. Thought should be given to introducing alternative models of paramedic practice, such as community paramedicine, with a focus on supporting people in the community with mental health and/or AOD problems. There is a need for a change in workplace and organisational culture about scope of practice in caring for patients with these problems. Extending paramedics' role could, potentially, benefit people with these problems by improving the quality of care, reducing the need for transportation to emergency departments, and decreasing clinicians' workloads in these departments.


An increasing need for goods and passenger transportation drives continued worldwide growth in traffic. As traffic increases environmental concerns, traffic safety, and cost efficiency become ever more important. Advancements in microelectronics open the possibility to address these issues through new advanced driver assistance systems. Applications such as predictive cruise control, automated gearbox control, predictive front lighting control, and hybrid vehicle state-of-charge control decrease the energy consumption of vehicles and increase the safety. These control systems can benefit significantly from preview road grade information. This information is currently obtained using specialized survey vehicles, and is not widely available. This thesis proposes new methods to obtain road grade information using on-board sensors. The task of creating road grade maps is addressed by the proposal of a framework where vehicles using a road network collect the necessary data for estimating the road grade. The estimation can then be carried out locally in the vehicle, or in the presence of a communication link to the infrastructure, centrally. In either case the accuracy of the map increases over time, and costly road surveys can be avoided. This thesis presents a new distributed method for creating accurate road grade maps for vehicle control applications. Standard heavy duty vehicles in normal operation are used to collect measurements. Estimates from multiple passes along a road segment are merged to form a road grade map, which improves each time a vehicle retraces a route. The design and implementation of the road grade estimator are described, and the performance is experimentally evaluated using real vehicles. Three different grade estimation methods, based on different assumption on the road grade signal, are proposed and compared. They all use data from sensors that are standard equipment in heavy duty vehicles. Measurements of the vehicle speed and the engine torque are combined with observations of the road altitude from a GPS receiver, using vehicle and road models. The operation of the estimators is adjusted during gearshifts, braking, and poor satellite coverage, to account for variations in sensor and model reliability. The estimated error covariances of the road grade estimates are used together with their absolute positions to update a stored road grade map. Highway driving trials show that the proposed estimators produce accurate road grade data. The estimation performance improves as the number of road segment traces increases. A vehicle equipped with the proposed system will rapidly develop a road grade map for its area of operation. Simulations show that collaborative generation of the third dimension for a pre-existing large area two-dimensional map is feasible. The experimental results indicate that road grade estimates from the proposed methods are accurate enough to be used in predictive vehicle control systems to enhance safety, efficiency, and driver comfort in heavy duty vehicles. The grade estimators may also be used for on-line validation of road grade information from other sources. This is important in on-board applications, since the envisioned control applications can degrade vehicle performance if inaccurate data are used.


A must-have guide that covers all the new features of Visual Studio 2010 Visual Studio allows you to create and manage programming projects for the Windows platform, and the new 2010 version has undergone a major overhaul comprised of significant changes. Written by an author team of veteran programmers and developers, Professional Visual Studio 2010 gets you quickly up to speed on what you can expect from the newest version of Visual Studio. This book's first section is dedicated to familiarizing you with the core aspects of Visual Studio 2010. Everything you need is contained in the first five chapters, from the IDE structure and layout to the various options and settings you can change to make the user interface synchronize with your own way of doing things. From there, the remainder of the book is broken into 11 parts: Getting Started: In this part, you learn how to take control of your projects and organize them in ways that work with your own style. Digging Deeper: Though the many graphical components of Visual Studio that make a programmer's job easier are discussed in many places throughout this book, you often need help when you're in the process of actually writing code. This part deals with features that support the coding of applications such as IntelliSense, code refactoring, and creating and running unit tests In the latest version of the .NET framework, enhancements were added to support dynamic languages and move towards feature parity between the two primary .NET languages, C# and VB. This part covers changes to these languages, as well as looking at a range of features that will help you write better and more consistent code. Rich Client and Web Applications: For support building everything from Office add-ins to cloud applications, Visual Studio enables you to develop applications for a wide range of platforms. These two parts cover the application platforms that are supported within Visual Studio 2010, including ASP.NET and Office, WPF, Silverlight 2 and ASP.NET MVC. Data: A large proportion of applications use some form of data storage. Visual Studio 2010 and the .NET Framework include strong support for working with databases and other data sources. This part examines how to use DataSets, the Visual Database Tools, LINQ, Synchronization Services and ADO.NET Entity Framework to build applications that work with data. It also shows you how you can then present this data using Reporting. Application Services: Through the course of building an application you are likely to require access to services that may or may not reside within your organization. This part covers core technologies such as WCF, WF, Synchronization Services and WCF RIA services that you can use to connect to these services. Configuration and Internationalization: The built-in support for configuration files allows you to adjust the way an application functions on the fly without having to rebuild it. Furthermore, resource files can be used to both access static data and easily localize an application into foreign languages and cultures. This part of the book shows how to use .NET configuration and resource files. Debugging: Application debugging is one of the more challenging tasks developers have to tackle, but correct use of the Visual Studio 2010 debugging features will help you analyze the state of the application and determine the cause of any bugs. This part examines the rich debugging support provided by the IDE. Build and Deployment: In addition to discussing how to build your solutions effectively and getting applications into the hands of your end users, this part also deals with the process of upgrading your projects from previous versions. Customizing and Extending Visual Studio: If the functionality found in the previous part isn't enough to help you in your coding efforts, Microsoft has made Visual Studio 2010 even more extensible. This part covers the automation model, how to write add-ins and macros, and then how to use a new extensibility framework, MEF, to extend Visual Studio 2010. Visual Studio Ultimate: The final part of the book examines the additional features only available in the Premium and Ultimate versions of Visual Studio 2010. In addition, you'll also learn how the Team Foundation Server provides an essential tool for managing software projects. Though this breakdown of the Visual Studio feature set provides the most logical and easily understood set of topics, you may need to look for specific functions that will aid you in a particular activity. To address this need, references to appropriate chapters are provided whenever a feature is covered in more detail elsewhere in the book. Professional Visual Studio 2010 is for all developers new to Visual Studio as well as those programmers who have some experience but want to learn about features they may have previously overlooked. If you are familiar with the way previous versions of Visual Studio worked, you may want to skim over Part I, which deals with the basic constructs that make up the user interface, and move on to the remainder of the book where the new features found in Visual Studio 2010 are discussed in detail. While you may be familiar with most of Part I, it is worth reading this section in case there are features of Visual Studio 2010 that you haven't seen or used before. If you're just starting out, you'll greatly benefit from the first part, where basic concepts are explained and you're introduced to the user interface and how to customize it to suit your own style.


A tube in a radiant superheater, the boiler of which is coal fired, failed by creep after 17 years of service. The failed tube was specified to be made of ASME SA-213, grade T-22. Measurable swelling of the tube diameter by about 2.4 mm and tube wastage caused by corrosion or erosion were observed. Log stress versus Larson-Miller Parameter (LMP) plots were produced to assess the remaining life of the superheater. It was revealed that the estimated operating temperature of 1060 deg F was higher than the estimated design temperature of 1000 deg F and that the tube wastage had increased the actual operating stress. Tube wastage and high operating temperatures hastened the failure. A better understanding of the material condition of this superheater was recommended to verify all the suspect hot tubes.


Experimental designs for a solar domestic hot water storage system were built in efforts to maximize thermal stratification within the tank. A stratified thermal store has been shown by prior literature to maximize temperature of the hot water drawn from the tank while simultaneously increasing the temperature delta required for effective heat transfer from the solar panels, thereby improving the annual performance of domestic solar hot water heating systems (DSHWH) by 30%–60%. Our design incorporates partitions, thermal diodes, and a coiled heat exchanger enclosed in an annulus. The thermal diodes are passive devices that promote natural convection currents of hot water upwards, while inhibiting reverse flow and mixing. Several variations of heat exchanger coils, diodes and partitions were simulated using ANSYS Computational Fluid Dynamics, and benchmarked using experimental data. The results revealed that the optimum design incorporated two partitions separated by a specific distance with four diodes for each partition. In addition, it was discovered that varying the length and diameter of the thermal diodes greatly affected the temperature distribution. The thermal diodes and partitions were used to maintain stratification for long periods of time by facilitating natural convective currents and taking advantage of the buoyancy effect. The results of the experiment and simulations proved that incorporating these elements into the design can greatly improve the thermal performance and temperature stratification of a domestic hot water storage tank.© 2012 ASME


Abstract. Validation of cloud properties retrieved from passive spaceborne imagers is essential for cloud and climate applications but complicated due to the large differences in scale and observation geometry between the satellite footprint and the independent ground based or airborne observations. Here we illustrate and demonstrate an alternative approach: starting from the output of the COSMO-EU weather model of the German Weather Service realistic three-dimensional cloud structures at a spatial scale of 2.33 km are produced by statistical downscaling and microphysical properties are associated to them. The resulting data sets are used as input to the one-dimensional radiative transfer model libRadtran to simulate radiance observations for all eleven low resolution channels of MET-8/SEVIRI. At this point, both cloud properties and satellite radiances are known such that cloud property retrieval results can be tested and tuned against the objective input "truth". As an example, we validate a cloud property retrieval of the Institute of Atmospheric Physics of DLR and that of EUMETSAT's Climate Monitoring Science Application Facility CMSAF. Cloud detection and cloud phase assignment perform well. By both retrievals 88% of the pixels are correctly classified as clear or cloudy. The DLR algorithm assigns the correct thermodynamic phase to 95% of the cloudy pixels and the CMSAF retrieval to 84%. Cloud top temperature is slightly overestimated by the DLR code (+3.1 K mean difference with a standard deviation of 10.6 K) and to a very low extent by the CMSAF code (−0.12 K with a standard deviation of 7.6 K). Both retrievals account reasonably well for the distribution of optical thickness for both water and ice clouds, with a tendency to underestimation. Cloud effective radii are most difficult to evaluate but the APICS algorithm shows that realistic histograms of occurrences can be derived (CMSAF was not evaluated in this context). Cloud water path, which is a combination of the last two quantities, is slightly underestimated by APICS, while CMSAF shows a larger scattering.


INTRODUCTION Stress may affect health negatively. Therefore, it is important to identify risks factors for high levels of stress. Previous studies indicate that parents report higher levels of stress than adults without children. Whether this it due to having children or due to other circumstances is unknown. The purpose of this study is to investigate whether parents have higher levels of stress than adults without children after controlling for possible confounders. A possible interaction between being a parent and working time on perceived stress will be examined. METHODS Cross-sectional data from Danish Health and Morbidity Survey 2000 were used. 3,083 men and 2,813 women aged 25-49 years answered one question on perceived stress. All analyses were stratified on sex and marital status and adjusted for age, socio-economic level, income and work hours/week. RESULTS No differences in perceived stress between men and women with and without children were found. Women, who were lone parents and worked more than 37 hours a week, had a markedly increased level of stress (OR: 3.2, 95%CI: (1.3-7.8)) compared to single women without children working 37 hours a week. CONCLUSION Children in the household did not appear to be the cause of a high level of perceived stress. Single mothers with long working hours were an exception to this conclusion.


Belief networks are commonly used generative models of data, but require expensive posterior estimation to train and test the model. Learning typically proceeds by posterior sampling, variational approximations, or recognition networks, combined with stochastic optimization. We propose using an online Monte Carlo expectationmaximization (MCEM) algorithm to learn the maximum a posteriori (MAP) estimator of the generative model or optimize the variational lower bound of a recognition network. The E-step in this algorithm requires posterior samples, which are already generated in current learning schema. For the M-step, we augment with Polya-Gamma (PG) random variables to give an analytic updating scheme. We show relationships to standard learning approaches by deriving stochastic gradient ascent in the MCEM framework. We apply the proposed methods to both binary and count data. Experimental results show that MCEM improves the convergence speed and often improves hold-out performance over existing learning methods. Our approach is readily generalized to other recognition networks.


Short-chain fatty acids (SCFA; acetate, propionate, and butyrate) are generated in colon by bacterial fermentation of dietary fiber. Though diffusion in protonated form is a significant route, carrier-mediated mechanisms constitute the major route for the entry of SCFA in their anionic form into colonic epithelium. Several transport systems operate in cellular uptake of SCFA. MCT1 (SLC16A1) and MCT4 (SLC16A3) are H+-coupled and mediate electroneutral transport of SCFA (H+: SCFA stoichiometry; 1:1). MCT1 is expressed both in the apical membrane and basolateral membrane of colonic epithelium whereas MCT4 specifically in the basolateral membrane. SMCT1 (SLC5A8) and SMCT2 (SLC5A12) are Na+-coupled; SMCT1-mediated transport is electrogenic (Na+: SCFA stoichiometry; 2:1) whereas SMCT2-mediated transport is electroneutral (Na+: SCFA stoichiometry; 1:1). SMCT1 and SMCT2 are expressed exclusively in the apical membrane. An anion-exchange mechanism also operates in the apical membrane in which SCFA entry in anionic form is coupled to bicarbonate efflux; the molecular identity of this exchanger however remains unknown. All these transporters are subject to regulation, notably by their substrates themselves; this process involves cell-surface receptors with SCFA as signaling molecules. There are significant alterations in the expression of these transporters in ulcerative colitis and colon cancer. The tumor-associated changes occur via transcriptional regulation by p53 and HIF1α and by promoter methylation. As SCFA are obligatory for optimal colonic health, the transporters responsible for the entry and transcellular transfer of these bacterial products in colonic epithelium are critical determinants of colonic function under physiological conditions and in disease states. © 2018 American Physiological Society. Compr Physiol 8:299-314, 2018.


An optical-lever technique was used to stabilize the retinal image, in order to determine spatial contrast-transfer functions for several modes of presentation of rectangularly and sinusoidally modulated bar patterns. These modes include a sudden replacement of a uniform field by a bar pattern, the replacement of a bar pattern by a uniform field, the intermittent presentation of a bar pattern at several repetition rates, and the sudden superposition of a uniform field on a bar pattern. Average retinal illuminances of 50 and 5 td were used. The outcomes of these experiments enable us to decompose the spatial contrast-transfer function for the case of normal vision into a branch due to the positive primary image and a branch due to a negative afterimage. The interaction of the primary image and the afterimage causes spatial transients in the image to be enhanced.


The Cell BE processor has proved that heterogeneous multi-core systems can provide a huge computational power with high efficiency for a wide range of applications. The simple design of the computational units and the use of small managed local memories is the key to achieve high efficiency and performance at the same time. However, this simple and efficient hardware design comes at the price of higher code complexity. The code written to run in this kind of processors must deal with several issues such as code vectorization, loop unrolling or the explicit management of local memories. Some of these issues such as vectorization or loop unrolling can be partially solved by the compiler, but the overlapping of data transfer and computation times must be manually addressed by the programmer with techniques such as double buffering that increase the code complexity. In this paper we present a user level threading library called CellMT that effectively hide memory latencies. The concurrent execution of several threads inside each SPU naturally overlaps computation and data transfer times without increasing the code complexity. To prove the suitability and feasibility of our multi-threaded library, we perform an exhaustive performance evaluation with a synthetic benchmark and a real application. The experimental results show that the multithreaded approach can outperform a hand-coded double buffering scheme, with speedups from 0.96x to 3.2x, while maintaining the complexity of a naive buffering scheme.


Mercury PollutionMercury has beguiled people for centuries, but the heavy metal also poses serious health and environmental dangers. This week, three stories in Science examine issues surrounding the new Minamata Convention on Mercury, which aims to curb emissions of the dangerous toxin and jump-start research. But it also faces numerous obstacles.


Collecting information of ecological and behavioural processes often requires continuous field monitoring, however, reiterative human presence necessary to obtain monitoring data can disturb both the environment and the study species. An example of this phenomenon is the monitoring of the formation and dynamics of seabird colonies; one of the reasons for colony failure is disturbances caused by the presence of researchers or conservation managers during data collection. In this study, an Unmanned Aircraft System (UAS) was used throughout the breeding period to monitor the temporal and spatial dynamics of a black-headed gull colony in the interior of a difficult-to-access island. This methodology permitted weekly visits to the colony without disturbance, which allowed for the continuous collection of spatial and temporal data on the process of colony formation. We obtained detailed information about nesting success and its relation with the distance to the nearest incubating neighbour, as well as the colony boundary along breeding season. Thus, we successfully monitored the dynamics of a bird colony and identified factors affecting individual decision making in colony formation using a UAS.

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We study the behavior of 12 pairs of undergraduate students while they were involved in a simple coordination game requiring motor interaction. Three experimental conditions were defined according to whether a monetary prize was given to both or only one subject, if the couple was in successfully completing the required assignment. Electromyographic potentials (EMG) were recorded from the right first dorsal interosseus (FDI) muscle, a muscle critically involved in the motor task. We also collected written answers from a standard questionnaire from which we constructed individual measures of Social Capital (SC), based on organized group interaction, religious and political involvement. These measures are collected, by standard practice, to estimate individual pro-social attitudes and behavior. Consistently with our simple behavioral model, by which EMG signals are direct measures of subjects' personal concern (call it utility) associated to the given task, our evidence shows that EMG is increasing in the subjects' own monetary reward. When we split the subject pool into two subsamples (according to various measures of Social Capital obtained from the questionnaire), we find that monetary incentives explain the level of subjects' EMG only in the subsample characterized by low SC, while, for subjects with (comparatively) higher SC, effort in the coordination task is much less sensitive to whether it is directly rewarded or not. This result is robust across the different SC index specifications. The present findings seem to support the possibility that an electrophysiological measure, such as EMG, could reveal the most profound attitudes and believes that guide social interaction, and that our relatively inexpensive and ready-to-use technology can back-up socio-economic research in a very effective way.


Appraisers often use discounted cash flow (DCF) techniques to value timber and timberland. Land expectation value (LEV) is a standard DCF technique applied to many timberland situations. LEV calculates the value of bare land in perpetual timber production and is often used to value even- aged pine plantations. However, it is also useful in the valuation of immature timber stands and uneven-aged timber stands cut periodically. These models have wide applicability in timberland appraisal situations. LEV as used to estimate the oportunity costs or varoius management regimes for pinnus pinaster forestry in several locations in Portugal. We made modelation to estimate present value of costs and revenues from an infinite series of identical even-aged forest rotations starting from bare land and take a Forest Value (a generalization of LEV): the present value of a property with an existing stand of trees plus the present value of a LEV for all future rotations of timber that will be grown on the property after harvesting the current stand. So we determine when a given stand should be cut; separate the management of the current stand from that of future stands and account for price changes that might occur during the life of the current stand. We will still assume that the rotations and prices associated with the future stands (i.e., the stands that are established after the current stand is cut) will be the same. We show some exemples os land value and timber value for the pinnus pinaster forestry.


Phishing is a con game that scammers use to collect personal information from unsuspecting users. The falsee-mails often look surprisingly legitimate and even the Web pages where users are asked to enter their information may look real. Phishing is similar to fishing in a lake, but instead of trying to capture fish, phishers attempt to steal personal information. This paper gives brief information about phishing, its attacks, steps that users can take to safeguard their confidential information. This paper also shows a survey conducted by netcraft on phishing


A survey of sustainable cereal/livestock farmers in South-Eastern Australia in 1985-86 is described in this study.

The first conclusion is that the average net financial results of producers who farm without the use of synthetic fertilisers and pesticides can not be seen to be different from those obtained on comparable conventional farms in 1985-86.

The sustainable farms were in areas with similar climate and soil quality (as measured by improved capital value per hectare) to that of their conventional counterparts. The use of less fertilisers per cropped unit of land on sustainable farms is therefore not due to the intrinsic quality of the land, but to a conscious decision to adopt an approach to farming very different from the conventional production system. The fact that some farmers tending towards sustainable practices, especially those in relatively marginal cropping areas, were still using some synthetic fertilisers indicates that not all problems have been solved regarding soil fertility and alternatives to conventional inputs.

Several methods were used by sustainable farmers to prevent loss of soil fertility. First, the percentage of arable area cropped was kept down. On average the fully sustainable (fs) farmers cropped less than half of the arable area, while the conventional neighbours of the fs farmers (the cfs farmers) cropped more than three quarters. All of the fs farmers cropped less than their conventional counterparts. This was not true for the semi-sustainable (ss) producers, whose cropping percentages were, on average, much closer to those of their conventional counterparts (css).

Soil fertility was also maintained by the use of animals. However, no statistically significant differences in number of livestock were recorded between the two systems per hectare grazed.

A third possible method of maintaining soil fertility is by diversifying crops. Although no statistical differences in number of crops were recorded, the percentage of cropped area in wheat was lower on sustainable than on conventional farms.

Most of these management tools (levels of cropping and stocking, and diversification of cropping) can be used not only to solve soil fertility problems, but also in the battle against pests. With regard to mechanical pest management, differences in cultivation practices were not immediately obvious from figures on fuel costs per hectare cropped. Also timing of cultivation was similar in the two systems, although sustainable farmers tended more towards the use of tined implements.

The differences in management practices did not lead to significant differences in yields. However, the sustainable farmers did obtain lower receipts from cropping per hectare operated. This was due to a smaller cropped area as a percentage of arable area. These lower receipts are at least partly compensated for by lower input costs of fertilisers, pesticides, and especially machinery and equipment.

Receipts from livestock per hectare operated were similar under the two management systems, for those pairs of farmers where both kept stock. When all eight fs and cfs farmers are included a difference can be shown for this variable.

Overall, the total cash costs of sustainable farming were significantly lower than those of conventional farming. Total cash receipts, though not different between the two systems for the fs-cfs and ss-css farmers separately, was higher for the conventional farmers if all 13 farmers were pooled. The bottom line, return to capital and management adjusted for interest and rent, was that a difference between the two systems could not be shown statistically.

Apart from indications of differences between sustainable and conventional farmers, a picture of differences between the fs and ss group of farmers emerged. The css farmers, although selected in the same way as the cfs producers, showed some characteristics distinct from those encountered amongst the cfs farmers. On average, the pattern of inputs for the css farmers indicates that it is likely that they farm in more marginal areas than cfs producers (for example, relatively low land prices), where cropping is relatively extensive (for example, relatively low use per hectare cropped of pesticides, fuel, machinery and equipment, and labour).

The question could be asked whether there is a causal relationship between the degree of adoption of sustainable farming and the degree of marginality of the area. If a relationship could be established, the question arises whether the reasons for such a relationship are agronomic problems, or whether they are different in nature. For example, in marginal cropping areas the area in crop per farm is relatively large, with low returns per hectare. Although input costs per hectare are also low, total expenditure on inputs per average farm is relatively high. This could imply that higher risks are taken by sustainable farmers in marginal areas than by those in non-marginal area when adopting a management system about which little information is available. It is only when the cause of a relationship between the degree of acceptability of the sustainable system and the degree of the area's suitability for cropping is established, that a beginning can be made with answering the question about the limits of sustainable agriculture.

It is unlikely that differences between practitioners of the two systems in formal and informal education, experience, and knowledge of local conditions influenced the relative financial returns of the two types of farming. Likely differences in management skills between some pairs of farmers probably depressed average returns on sustainable farms. It is also likely that lack of information about sustainable farming negatively influenced the financial returns from this type of farm system.
In summary, the results from the survey indicate that net private financial benefits from sustainable farming were similar to those in the conventional sector in certain areas in 1985-86. This was the case despite lack of information about the sustainable management system, and despite the fact that some conventional farmers were likely to be better managers than their sustainable farmer counterparts.


An adaptive learning approach for the computation of the coefficients of the generalized nonorthogonal 2-D Gabor (1946) transform representation is introduced. The algorithm uses a recursive least squares (RLS) type algorithm. The aim is to achieve minimum mean squared error for the reconstructed image from the set of the Gabor coefficients. The proposed RLS learning offers better accuracy and faster convergence behavior when compared with the least mean squares (LMS)-based algorithms. Applications of this scheme in image data reduction are also demonstrated.


Space, location, coordinates, distance: these interrelated concepts and their practical realisations in data structures, analytical procedures, and visualization techniques arecentral to what computation is able to achieve in geographical research. We argue the ideals and approaches of GeoComputation have much to contribute to the realisation of a geographical computation that embraces not only the representation and analysis of phenomena in absolute, Euclidean space, but can engage relative and relational spaces as well. Such spaces emerge with process and relation, and they were viewed as central toadvancing geographical research during the quantitative revolution. We present results of initial steps taken in this geocomputational research agenda: we formalise, implement, exemplify, and analyse a generalized, empirical projection approach appropriate to translating between the (sometimes complicated and emergent) coordinate systems of relational, relative, and absolute spaces.


The remarkable growth spurt reported by the Sub-Saharan African (SSA) economy since the mid-1990s offers the opportunity to revisit the narrative of its economic development experience. We investigate whether the SSA economy has initiated a gradual process of convergence which reverses the long-term fall so far behind the U.S. frontier. Our framework begins with a top-down approach that performs a nested development accounting exercise. This aggregate analysis complements a bottom-up approach that tracks the sectoral origins of the SSA aggregate relative labor productivity performance. The application of this framework to a representative sample of the SSA economy over the 1970-2010 period suggests the following set of results. After one-quarter of a century of falling behind the U.S. level of real income per capita, the SSA economy observed a swift turnaround towards the end of the 1990s, yet without showing any sign of catch-up. Second, parallel to favorable demographic developments, SSA reports a startling relative labor productivity gap which accounts for much of its relative income per capita gap. Third, the use of the concept of cognitive skills reveals that human capital considerations have worsened o_ over time, making total factor productivity no longer the biggest part of the story underlying relative labor productivity differences. Fourth, the sectoral evidence points to the coexistence of headwinds (negative within- and reallocation-effects) and tailwinds (between-effects) which tend to cancel out each other, thus preventing SSA aggregate economic performance to get anywhere closer to the world frontier even during the growth spurt period.


I propose a new conceptual framework to disentangle the impacts of weather and climate on economic activity and growth: A stochastic frontier model with climate in the production frontier and weather shocks as a source of inefficiency. I test it on a sample of 160 countries over the period 1950-2014. Temperature and rainfall determine production possibilities in both rich and poor countries; positively in cold countries and negatively in hot ones. Weather anomalies reduce inefficiency in rich countries but increase inefficiency in poor and hot countries; and more so in countries with low weather variability. The climate effect is larger that the weather effect.


This study focused on the severity of injuries and fatalities incurred by pedestrians colliding with motor vehicles. The report includes a thorough review of the literature and a description of new research carried out on correlates of injury severity and measures of their relative effects on fatal or high injury collisions. The correlates consisted of both individual-level factors and attributes of environments at or near pedestrian collision sites. The study focused on state routes in King County, Washington. Data came from police records processed by the Washington State Department of Transportation (WSDOT) from 1999 to 2004. They included objective and modeled data in GIS on road characteristics, traffic conditions, and land uses at or near collision sites. The results of binary and ordinal logistic models showed that fatal and high injury collisions were strongly and significantly associated with (1) a pedestrian crossing at an unsignalized intersection (versus crossing at all other locations or walking along the roadway); (2) the vehicle moving straight ahead on the roadway (versus all other types of vehicle actions). There was a lack of association between injury severity and collision frequency, suggesting that safety programs intended to reduce the number of collisions and those intended to reduce the risk of severe injury and death should use different approaches. The latter should focus on individual factors such as driver or pedestrian actions and behaviors, as well as on road environment factors such as speed limits and intersection signalization. Finally, better reports and data on vehicular speed at the time of collision, and on the type of vehicles involved in pedestrian collisions, would help to inform effective future safety programs, policies, and standards.


Prior to CoP 10, our discussion paper ?On the Integration of Carbon Capture and Storage into the International Climate Regime? argued that carbon capture and storage (CCS) was similar to carbon sequestration in the area of Land Use, Land-Use Change and Forestry (LULUCF). This was criticized by several readers who observed that treating CCS as a removal activity (sink) would not be compatible with the UNFCCC sink definition, what we already had mentioned in the paper. The present paper is based on the UNFCCC definition and analyses how CCS could be integrated into the climate regime. As CO2 may re-enter the atmosphere after injection into geological reservoirs, the question of long-term liability has to be considered. Apart from this aspect, additional complexities arise from the fact that CO2 capture and storage can be carried out in two different countries. A classification of CCS cross-border activities shows that not all cases with non-Annex I participation fall under the CDM. Furthermore, we elaborate on the problem that seepage of CO2 from reservoirs located in non-Annex I countries – under current rules – would not be subtracted from the emission budget of any country. For these cases, solutions guaranteeing liability for possible non-permanence of CCS are proposed.


I decided to make you familiar with an aspect of American property law. You may not realize that a formalistic approach is taken regarding the necessity of consent to form contracts often presented to consumers, including subprime mortgage borrowers who signed the notes (which are themselves contracts) and mortgage documents to transfer the property to lenders. Because many who give what is known as objective consent ie they sign the paper incorporating an agreement, but they do not understand the terms of the contract or the impact on them, I argue that the form contract may protect businesses that use these, but not the property of those consumers/borrowers. These types of "take it or leave it" contracts are known as adhesion contracts. In subprime mortgages lenders offer borrowers form contracts (promissory notes) which the borrower must sign in order to obtain the loan. There is no negotiation of the terms of the note or the mortgage document.A significant part of the subprime crisis in residential real estate in the United States is due to a lack of subjective consent to the contracts entered into regarding the subprime mortgage loans. Then, of course because of globalization of investments this economic crisis affected investors worldwide. As was presented at the meeting of the Italian Civil Law Notaries in Torino in January 2008, many of these global investors trusted the US regulators and U.S. ratings agencies only to learn that neither was working effectively or as investors believed.


Brief discussions of previous investigations in the aerospace sciences and technical comments on papers published in the AIAA Journal are presented in this"special department. Entries must be restricted to a maximum of WOO words, or the equivalent of one Journal page including formulas and figures. A discussion mil be published as quickly as possible after receipt of the manuscript. Neither the AIAA nor its editors are responsible for the opinions expressed by the correspondents. Authors will be invited to reply promptly.


Diminishing water supply, changing weather patterns and pressure to enhance environmental flows are making it imperative to optimise water use efficiency (WUE) on cotton/grain farming systems. Growers are looking for better strategies to make the best use of limited water, but it is still not clear how to best use the available water at farm and field scale. This research project investigated the impact of management strategies to deal with limited water supplies on the yield and quality of irrigated cotton and wheat. The objectives were: (1) to develop irrigation management guidelines for the main irrigated crops on the Darling Downs for full- and deficitirrigation scenarios, taking into account the critical factors that affect irrigation decisions at the local level, (2) to quantify the evapotranspiration (ET) of Bollgard II cotton and wheat and its relationship to yield and quality under full- and deficit-irrigation scenarios, and (3) to increase industry awareness and education of farming systems practises for optimised economic water use efficiency.Objective (1) was addressed by (A) collaborating with ASPRU to develop the APSFarm model within APSIM to be able to perform multi-paddock simulations. APSFarm was then tested by conducting a case study at a farm near Dalby, and (B) conducting semi-structured interviews with individual farmers and crop consultants on the Darling Downs to document the strategies they are using to deal with limited water. Objective (2) was addressed by (A) building and installing 12 large (1 m x 1m x 1.5 m) weighing lysimeters to measure crop evapotranspiration. The lysimeters were installed at the Agri-Science Queensland research station at Kingsthorpe in November 2008, (B) conducting field experiments to measure crop evapotranspiration and crop development under four irrigation treatments, including dryland, deficit-irrigation, and full irrigation. Field experiments were conducted with cotton in 2007-08 and 2008-09, and with wheat in 2008 and 2009, and (C) collaborating with USQ on a PhD thesis to quantify the impact of crop stress on crop evapotranspiration and canopy temperature. Glasshouse experiments were conducted with wheat in 2008 and with cotton in 2008-09. Objective (3) was addressed by (A) conducting a field day at Kingsthorpe in 2009, which was attended by 80 participants, (B) presenting information in conferences in Australia and overseas, (D) presenting information at farmers meeting, (E) making presentations to crop consultants, and (F) preparing extension publications.As part of this project we contributed to the development of APSfarm, which has been successfully applied to evaluate the feasibility of practices at the whole-farm scale. From growers and crop consultants interviews we learned that there is a great variety of strategies, at different scales, that they are using to deal with limited water situation. These strategies will be summarised in the qLimited Water Guidelines for the Darling Downsq that we are currently preparing. As a result of this project, we now have a state-of-the-art lysimeter research facility (23 large weighing lysimeters) to be able to conduct replicated experiments to investigate daily water use of a variety of crops under different irrigation regimes and under different environments. Under this project, a series of field and glasshouse experiments were conducted with cotton and wheat, investigating aspects like: (A) quantification of daily and seasonal crop water use under nonstressed and stressed conditions, (B) impact of row configuration on crop water use, (C) impact of water stress on yield, evapotranspiration, crop vegetative and reproductive development, soil water extraction pattern, yield and yield quality. The information obtained from this project is now being used to develop web-based tools to help growers make planning and day-to-day irrigation decisions.


The debate over modernist music has continued for almost a century: from Strauss's Elektra and Webern's Symphony Op.21 to John Cage's renegotiation of musical control, the unusual musical practices of the Velvet Underground, and Stanley Kubrick's use of Ligeti's Lux Aeterna in the epic film 2001. The composers discussed in these pages -- including Bartok, Stockhausen, Bernard Herrmann, Steve Reich, and many others -- are modernists in that they are defined by their individualism, whether covert or overt, and share a basic urge toward redesigning musical discourse. The aim of this volume is to negotiate a varied and open middle ground between polemical extremes of reception. The contributors sketch out the possible significance of a repertory that in past discussions has been deemed either meaningless or beyond describable meaning. With an emphasis on recent aesthetics and contexts -- including film music, sexuality, metaphor, and ideas of a listening grammar -- they trace the meanings that such works and composers have held for listeners of different kinds. None of them takes up the usual mandate of "educated listening" to modernist works: the notion that a person can appreciate "difficult" music if given enough time and schooling. Instead the book defines novel but meaningful avenues of significance for modernist music, avenues beyond those deemed appropriate or acceptable by the academy. While some contributors offer new listening strategies, most interpret the listening premise more loosely: as a metaphor for any manner of personal and immediate connection with music. In addition to a previously untranslated article by Pierre Boulez, the volume contains articles (all but one previously unpublished) by twelve distinctive and prominent composers, music critics, and music theorists from America, Europe, Australia, and South Africa: Arved Ashby, Amy Bauer, William Bolcom, Jonathan Bernard, Judy Lochhead, Fred Maus, Andrew Mead, Greg Sandow, Martin Scherzinger, Jeremy Tambling, Richard Toop, and Lloyd Whitesell Arved Ashby is associate professor of music at the Ohio State University.


Abstract Fresh and weathered pyrochlore from the Lueshe carbonatite complex (in the northeast of the Democratic Republic of Congo) was studied by Fourier transfom infrared (FTIR) spectroscopy and by a combination of FTIR spectroscopy and thermal analysis. The former was carried out in the spectral range 400-4000 cm-1. The spectra for fresh and weathered pyrochlores were very different. For the weathered pyrochlore, two bands were identified as OH vibration modes, one broad band with a maximum at 3413 cm-1 and another finer band at 1630 cm-1. The fresh pyrochlore does not show OH absorption bands. The presence of OH confirms the hydrated state of the weathered pyrochlore suggested by previous microanalytical work. The combination of FTIR spectroscopy and thermal analysis allows 'real-time' observation of gas emanations and solid-state transformations taking place during heating up to 800°C. For fresh pyrochlore, no solid transformation was detected, except a CO2 emanation from 242-576°C. For the weathered pyrochlore a dehydration was observed between 234-565°C followed by an exothermic peak in Differential Scanning Calorimetric (DSC) curve at 604°C. This exothermic peak corresponds to the formation of a Nb oxide phase. At higher temperatures the weathered pyrochlore is partly decomposed, forming a dehydrated pyrochlore and a Nb oxide phase. The combination of FTIR and thermal analysis has provided useful information on both fresh and weathered pyrochlore transformations which has clarified our understanding of the water control of the structural stability of pyrochlore minerals.


Background: Data on the efficacy of intercellular adhesion molecule-1 antisense oligonucleotide alicaforsen in ulcerative colitis (UC) is inconsistent. Methods: All patients, who had received at least one dose of alicaforsen, were analyzed retrospectively. Alicaforsen's efficacy was assessed in patients treated for left-sided UC and proctitis by comparing clinical and (if applicable) endoscopic disease activity before/after treatment. Results: Twelve patients were treated for left-sided UC or proctitis. Eleven patients received a 6-week course of a once-daily 240 mg alicaforsen enema formulation. In 1 patient, treatment was discontinued, because it was found to be inefficient. Disease activity measured by the partial Mayo score and 6-point symptom score was significantly reduced after treatment (6.0 vs. 2.4, p = 0.011 and 3.7 vs. 1.4, p = 0.008). Faecal calprotectin showed a trend towards reduction (484.4 vs. 179.5 μg/g, p = 0.063). Clinical improvement was achieved in 10 patients (83.3%). In 7 patients, a relapse occurred (70%). Median duration of clinical improvement was 18.0 weeks (range 1–112). Three patients showed an ongoing improvement of >9 months. No adverse events were reported. Conclusions: A 6-week course of alicaforsen seemed to be safe and efficacious in inducing clinical improvement in patients with left-sided UC and proctitis. Prolonged clinical improvement was observed in many but not all patients.