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The pharmaceutical industry is constantly striving for innovative ways to bridge the translational gap between preclinical and clinical drug development to reduce attrition. Substantial effort has focused on the preclinical application of human-based microphysiological systems (MPS) to better identify compounds not likely to be safe or efficacious in the clinic. The Coronavirus 2019 (COVID-19) pandemic provides a clear opportunity for assessing the utility of MPS models of the lungs and other organ systems affected by the disease in understanding the pathophysiology of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and in the development of effective therapeutics. Here, we review progress and describe the establishment of a global working group to coordinate activities around MPS and COVID-19 and to maximize their scientific, human health, and animal welfare impacts.

Although evaluations of members of parliaments’ (MPs) parliamentary work have gained increasing public popularity, the academic literature on the concept and measurement of parliamentary performance is surprisingly scarce. Most studies analysing (aspects of) MPs’ parliamentary performance focus on quantitative parliamentary activity indicators only, thereby neglecting the quality and effectiveness of parliamentary work, and the importance of less visible parliamentary activities. This article introduces a conceptual framework of parliamentary performance as well as a more encompassing measurement approach, and provides a first empirical test of theoretically expected underlying dimensions on 325 Belgian MPs. This study proposes an innovative method relying on the collective expertise of MPs through peer assessment while controlling for potential rater effects. I demonstrate that parliamentary performance cannot be captured by parliamentary activity indicators alone. Exploratory and confirmatory factor analyses show that apart from three factors of parliamentary activity, two more qualitative factors (content and policy-making effectiveness) can be identified. The results suggest that future evaluations of MPs’ parliamentary work may need to include more qualitative elements.

Метою статті є оцінювання рівня маніпулювання керівників та проявів макіавеллізму в трудовому колективі залежно від його соціально-демографічних характеристик. На основі теоретичного аналізу визначено три гіпотези щодо вивчення відмінностей між маніпуляціями та проявами макіавеллізму з точки зору місця проживання працівників (міських чи сільських), форми власності організації (приватної чи державної) та віку працівників. Вихідні дані дослідження сформовано на основі результатів опитування 123 респондентів. Для перевірки висунутих гіпотез застосовано методологічний інструментарій CASADI (розсудливість, самоствердження, дипломатичність) та шкалу макіавеллізму особистості (MPS). Використання CASADI дозволило визначити прояви макіавеллізму в бізнесі та управлінській поведінці на основі результатів оцінювання думки респондентів щодо маніпуляцій між людьми. Методологія MPS дозволила оцінити рівень маніпуляцій керівників. Практичну реалізацію усіх етапів дослідження здійснено за допомогою t-тесту та коефіцієнта кореляції Пірсона. Емпіричні розрахунки підтвердили наявність відмінностей у рівнях самоствердження, бажання контролю та недовіри залежно від місця проживання респондентів. У ході дослідження встановлено статистичну значущість між віковою різницею та проявом дипломатії відповідно до макіавеллізму, а також прагненні до соціального статусу при маніпуляціях керівників. Встановлено статистичну значущість для рівнів самоствердження та розсудливості (які є атрибутами прояву макіавеллізму), а також атрибутів маніпуляцій лідерів (аморальності, бажання контролювати та недовіри до інших) залежно від форми власності організації (приватної чи державної). Авторами наголошено, що працівники, які проживають у місті, мають вищий рівень макіавеллізму, про що свідчать мотивація до отримання прибутку, необхідність контролювати інших та недовіра. При цьому рівень макіавеллізму є обернено пропорційним до віку. Отримані результати засвідчили, що у працівників приватних організацій більш виражені прояви макіавеллізму. This research aims to assess the level of manipulation of leaders and Machiavellian manifestations in the work process within selected socio-demographic characteristics of employees. Based on the described theoretical basis, three hypotheses were established. The hypotheses concern is examining the differences between manipulation and Machiavellian manifestations regarding employees' residence (urban or rural), the sphere of the organization (private or public) in which they work, and the age of employees. The data were obtained through a questionnaire survey in which 123 respondents participated. The study involved methodological tools such as CASADI (Calculativness, Self-Assertion, Diplomacy) and MPS (Machiavellian Personality Scale). The new CASADI methodology identifies Machiavellian manifestations in business and managerial behavior. It contains statements that relate to the respondent's opinion on manipulation between people. The MPS methodology was created for leaders in determining the level of their manipulation through four factors determining Machiavellianism. The survey results were evaluated through a t-test and Pearson's correlation coefficient. The findings confirmed the differences in SelfAssertion, Desire for Control, and Distrust regarding respondents' residence. The study of age differences recorded the statistical significance for the attribute of Diplomacy within Machiavellian manifestations and the attribute of Desire for social status within the manipulation of leaders. Within the differences between the private and public spheres, statistical significance was recorded for the attributes of Machiavellian manifestations of Computation and SelfEnforcement, and for the attributes of the manipulation of leaders Amorality, Desire for Control and Distrust of others. The research results indicated that employees living in the city might have a higher degree of Machiavellianism. It is reflected in their motivation for for-profit and the need to control others and not trust them. Research suggested that the rate of Machiavellianism decreases with age. In the case of the organization activity where the employee works, it was found that Machiavellian tendencies were more pronounced in employees of the private sphere.

Introduction Sanfilippo syndrome (MPS III) is a rare, degenerative condition characterized by symptoms impacting cognitive ability, mobility, behavior, and quality of life. Currently there are no approved therapies for this severe life-limiting disease. Integrating patient and caregiver experience data into drug development and regulatory decision-making has become a priority of the Food and Drug Administration and rare disease patient communities. Methods This study assesses parents’ perceptions of their child’s Sanfilippo syndrome disease-related symptoms using a research approach that is consistent with the Center for Drug Evaluation and Research (CDER) guidance. This study was initiated by the Cure Sanfilippo Foundation, and all steps in the research process were informed by a multidisciplinary advisory committee, with an objective of informing biopharmaceutical companies and regulatory agencies. We explored caregiver burden, symptoms with greatest impact, and meaningful but unmet treatment needs. Data were collected from 25 parents through three focus groups and a questionnaire. Transcripts were coded and analyzed using inductive thematic analysis, and descriptive analysis of quantitative data was conducted. Results Participating parents’ children ranged in age from 4 to 36 years. Participants endorsed high caregiving burden across all stages of the disease. Analysis revealed multiple domains of unmet need that impact child and family quality of life, including cognitive-behavioral challenges in communication, relationships, behavior, anxiety, and child safety; and physical health symptoms including sleep, pain, and mobility. Participants reported placing high value on incremental benefits targeting those symptoms, and on a treatment that would slow or stop symptom progression. Conclusion Even modest treatment benefits for Sanfilippo syndrome were shown to be highly valued. Despite high caregiver burden, most parents expressed a willingness to “try anything,” including treatments with potentially high risk profiles, to maintain their child’s current state. Electronic supplementary material The online version of this article (10.1007/s40120-020-00226-z) contains supplementary material, which is available to authorized users.

Identification and approval of new drugs for use in patients requires extensive preclinical studies and clinical trials. Preclinical studies rely on in vitro experiments and animal models of human diseases. The transferability of drug toxicity and efficacy estimates to humans from animal models is being called into question. Subsequent clinical studies often reveal lower than expected efficacy and higher drug toxicity in humans than that seen in animal models. Microphysiological systems (MPS), sometimes called organ or human-on-chip models, present a potential alternative to animal-based models used for drug toxicity screening. This review discusses multi-organ MPS that can be used to model diseases and test the efficacy and safety of drug candidates. The translation of an in vivo environment to an in vitro system requires physiologically relevant organ scaling, vascular dimensions, and appropriate flow rates. Even small changes in those parameters can alter the outcome of experiments conducted with MPS. With many MPS devices being developed, we have outlined some established standards for designing MPS devices and described techniques to validate the devices. A physiologically realistic mimic of the human body can help determine the dose response and toxicity effects of a new drug candidate with higher predictive power.

In traditional clinical trial design, efficacy is typically assessed using a single primary endpoint in a randomized controlled trial to detect an expected treatment effect of a therapy in a narrowly selected patient population. This accepted paradigm is based on clinical evaluations that may not actually capture the breadth of the impact of a disease, which is especially true in the setting of complex, multisystem, rare diseases with small, extremely heterogeneous patient populations. The multi-domain responder index (MDRI) is a novel approach that accommodates complex and heterogeneous disease manifestations and evaluates a broad array of clinical disease without impairing the power or rigor of a study to fully understand a treatment. The MDRI sums the scores corresponding to clinically significant thresholds of change for each component domain in each individual patient, capturing the mean clinically meaningful change across multiple domains within individuals. This novel approach combines and then sums the results of independent domain endpoint responder analyses into one responder score to provide a broad basis for the assessment of efficacy. The impact of a treatment across multiple, physiologically independent domains, can be assessed clinically, reducing the adverse impact of heterogeneity on trial outcomes and allowing eligibility criteria to enroll a wider range of patients, ultimately resulting in efficacy and safety assessments of a therapy across a broad group of heterogeneous patients in rare disease programs.Trial registration The following studies are referenced within this manuscript (CLINICALTRIALS.GOV registration numbers): NCT00912925; NCT00146770; NCT00067470; NCT00104234; NCT00069641; NCT02230566; NCT02377921; NCT02432144.

The mucopolysaccharidoses (MPS) are a group of rare, genetic, lysosomal storage disorders characterized by progressive, multisystemic accumulation of glycosaminoglycans. Individuals with severe MPS often present with significant neurological involvement and may exhibit challenging behaviors, including hyperactivity, aggression, and sleep disturbance. These behaviors can cause adverse outcomes and necessitate the development of specific measures to support affected families. Through an analysis of the results reported by Hoffmann et al. in their recent study, this letter outlines important factors that must be considered when evaluating the impact of challenging behaviors associated with MPS, including treatment history, age, sibling and family relationships, the feasibility of daily caregiving, and caregiver burden. These recommendations can help guide future studies to identify the most effective coping strategies to support families of people with MPS who have challenging behaviors.

Background Mucopolysaccharidosis type III (MPS III) comprises a group of rare lysosomal storage diseases. Although musculoskeletal symptoms are less pronounced than in other MPS subtypes, pathologies of hip and spine have been reported in MPS III patients. The purpose of this study was to describe hip pathologies and influencing parameters in MPS III patients. Methods A retrospective chart review was performed for 101 MPS III patients. Thirty-two patients met the inclusion criteria of enzymatically or genetically confirmed diagnosis and anteroposterior radiograph of the hips. Modified Ficat classification, Wiberg’s center-edge angle, and Reimer’s migration percentage were measured. Results The mean age at data assessment was 11.0 years (SD 5.7). Osteonecrosis of the femoral head was observed in 17/32 patients. No statistically significant association was found between these changes and age, sex, or MPS III subtype. Patients with a severe phenotype showed significantly higher rates of osteonecrosis (14/17) than patients with an intermediate phenotype. Hip dysplasia was present in 9/32 patients and was significantly associated with osteonecrosis of the femoral head (p = 0.04). Conclusions The present study demonstrates a high rate of hip pathologies in MPS III patients. Hip dysplasia and severe phenotype were significantly correlated with osteonecrosis of the femoral head. Therefore, radiographs of the hips are highly recommended in baseline and follow-up assessments of MPS III patients. Trial registration Retrospectively registered.

The hips are frequently involved in inheritable diseases which affect the bones. The clinical and radiological presentation of these diseases may be very similar to common hip disorders as developmental dysplasia of the hip, osteoarthritis and avascular necrosis, so the diagnosis may be easily overlooked and treatment may be suboptimal. Mucopolysaccharidosis (MPS) and Mucolipidosis (ML II and III) are lysosomal storage disorders with multisystemic involvement. Characteristic skeletal abnormalities, known as dysostosis multiplex, are common in MPS and ML and originate from intra-lysosomal storage of glycosaminoglycans in cells of the cartilage, bones and ligaments. The hip joint is severely affected in MPS and ML. Hip pathology results in limitations in mobility and pain from young age, and negatively affects quality of life. In order to better understand the underlying process that causes hip disease in MPS and ML, this review first describes the normal physiological (embryonic) hip joint development, including the interplay between the acetabulum and the femoral head. In the second part the factors contributing to altered hip morphology and function in MPS and ML are discussed, such as abnormal development of the pelvic- and femoral bones (which results in altered biomechanical forces) and inflammation. In the last part of this review therapeutic options and future perspectives are addressed.

Cardiac amyloid is an uncommon cause of diastolic dysfunction the recognition of which requires the internist to have clinical suspicion to guide diagnosis and treatment. Cardiac amyloid is an infiltrative cardiomyopathy with significant morbidity and mortality. Appropriate diagnosis is important because management of cardiac amyloid differs from typical heart failure with preserved ejection fraction. An astute internist must be able to recognize common findings of cardiac amyloidosis. Here we present a case of a patient presenting with diastolic heart failure and the steps leading towards diagnosis and subsequent treatment.

Metalloproteinases (MPs) are proteolytic enzymes involved in extracellular matrix deposition, regulation of cellular signals of inflammation, proliferation, and apoptosis. Metalloproteinases are classified into three families: Matrix-MPs (MMPs), A-Disintegrin-and-Metalloprotease (ADAMs), and the A-Disintegrin-and-Metalloproteinase-with-Thrombospondin-1-like-Domains (ADAMTS). Previous studies showed that MPs are involved in the development of aortic aneurysms (AA) and, concomitantly, in the onset of chronic kidney disease (CKD). CKD has been, per se, associated with an increased risk for AA. The aim of this review is to examine the pathways that may associate MPs with CKD and AA. Several MMPs, such as MMP-2, -8, -9, and TIMP-1 have been shown to damage the AA wall and to have a toxic effect on renal tubular cells, leading to fibrosis. Similarly, ADAM10 and 17 have been shown to degrade collagen in the AA wall and to worsen kidney function via pro-inflammatory stimuli, the impairment of the Renin-Angiotensin-Aldosterone System, and the degradation of structural proteins. Moreover, MMP-2 and -9 inhibitors reduced aneurysm growth and albuminuria in experimental and human studies. It would be important, in the future, to expand research on MPs from both a prognostic, namely, to refine risk stratification in CKD patients, and a predictive perspective, likely to improve prognosis in response to targeted treatments.

Mucopolysaccharidosis (MPS) is a group of rare disorders that are characterized by intracellular accumulation of glycosaminoglycans with subsequent cellular and organ dysfunction. In the Middle East, especially Saudi Arabia, higher prevalence of MPS type I was observed compared to reported rates from European countries and the United States (U.S). The present work was developed as a part of the Saudi MPS Group’s efforts to address the current situation of MPS type I in Saudi Arabia and to reach a national consensus in the management of MPS type I. The first “Management of MPS Type I Advisory Board” meeting was held in Riyadh on May 2, 2019, to reflect the expert opinions regarding different aspects of MPS type I and develop this manuscript; eight consultants from different specialties (medical genetics, pediatric rheumatology, and pediatric endocrinology), representing six Saudi institutions, in addition to a global expert in genetics participated in the meeting.

Background: Mucopolysaccharidoses (MPS) are rare, inherited disorders associated with enzyme deficiencies that result in glycosaminoglycan (GAG) accumulation in multiple organ systems. Management of MPS is evolving as patients increasingly survive to adulthood and undergo multiple surgeries throughout their lives. As surgeries in these patients are considered to be high risk, this can result in a range of critical clinical situations in adult patients. Results: We discuss strategies to prepare for and manage critical clinical situations in adult patients with MPS, including supporting the multidisciplinary team, preoperative and airway assessments, surgical preparations, and postoperative care. We also present eight critical clinical cases (age range: 21–38 years) from four leading inherited metabolic disease centres in Europe to highlight challenges and practical solutions to optimise the care of adult patients with MPS. Critical clinical situations included surgical procedures, pregnancy and a thrombus in a port-a-cath. Conclusions: Individualised strategies to manage critical clinical situations need to be developed for each patient to compensate for the heterogeneous symptoms that may be present and the potential complications that may occur. These strategies should include input from the wider MDT, and be coordinated by metabolic specialists with expertise in the management of MPS disorders and surgery in adult patients with MPS.

Mucopolysaccharidosis type I (MPS I) is a hereditary metabolic disease that manifests itself in childhood by systemic damage to tissues and organs, a constantly progressive course leading to disability. Diagnosis of mild forms of the disease is particularly difficult due to the absence of specific symptoms. A specific symptom of the mild forms of MPS I (as for other types of MPS) is joint stiffness in children combined with hernia, frequent infections, or valvular defects. Stiffness in MPS I is often interpreted as a manifestation of rheumatological diseases (arthrogriposis, juvenile idiopathic arthritis). The article offers a simple algorithm for diagnosing MPS I, which helps to eliminate the disease using a simple test for determining the activity of an enzyme called alpha-L-iduronidase in a dried blood spot.

Enzyme replacement therapy (ERT) is available for mucopolysaccharidosis (MPS) I, MPS II, MPS VI, and MPS IVA. The efficacy of ERT has been evaluated in clinical trials and in many post-marketing studies with a long-term follow-up for MPS I, MPS II, and MPS VI. While ERT is effective in reducing urinary glycosaminoglycans (GAGs) and liver and spleen volume, cartilaginous organs such as the trachea and bronchi, bones and eyes are poorly impacted by ERT probably due to limited penetration in the specific tissue. ERT in the present formulations also does not cross the blood–brain barrier, with the consequence that the central nervous system is not cured by ERT. This is particularly important for severe forms of MPS I and MPS II characterized by cognitive decline. For severe MPS I patients (Hurler), early haematopoietic stem cell transplantation is the gold standard, while still controversial is the role of stem cell transplantation in MPS II. The use of ERT in patients with severe cognitive decline is the subject of debate; the current position of the scientific community is that ERT must be started in all patients who do not have a more effective treatment. Neonatal screening is widely suggested for treatable MPS, and many pilot studies are ongoing. The rationale is that early, possibly pre-symptomatic treatment can improve prognosis. All patients develop anti-ERT antibodies but only a few have drug-related adverse reactions. It has not yet been definitely clarified if high-titre antibodies may, at least in some cases, reduce the efficacy of ERT.

Background Mucopolysaccharidoses (MPS) are a group of rare inherited disorders characterized by abnormal accumulation of glycosaminoglycans (GAGs) within the myocytes and coronary arteries. Little is known about hyperlipidaemia as a potential cardiovascular risk factor in these patients. Baseline cholesterol data in adults are scarce. Therefore, the aim of this study was to analyse factors affecting lipid profile in different types of MPSs to determine if abnormalities in lipid profile contribute to the overall risk of cardiovascular disease. Methods Adult patients (above the age of 16) with MPS type I, II, III, IV and VI attending clinics in two Inherited Metabolic Disorders centres were included. Their lipid profile, lipoprotein (a), HbA1c, Glucose Tolerance Test (GTT), BMI and treatment type were extracted. Analysis included descriptive statistics and Student t-test. Results Eighty two patients with five MPS types (I, II, III, IV and VI) were included in the study; 29 were females (35%) and 53 were males (65%). BMI above 25 kg/m2 in all MPS types indicated that some patients were overweight for their height. Only one patient post-HSCT had diabetes. In 3 cases insulin was analysed during GTT and showed no insulin resistance despite raised BMI. Mean total cholesterol and LDL-cholesterol were below 5 mmol/L and 3 mmol/L, respectively, in five individual MPS types. Lipoprotein (a) was available for 6 MPS IV patients and was not significantly raised. Conclusions MPS disorders are not associated with significant hypercholesterolaemia or diabetes mellitus despite increased BMI. Total cholesterol and LDL-cholesterol were within the targets for primary prevention for non-MPS population. Lipoprotein (a) is not a useful marker of cardiovascular disease in a small group of adult MPS IV patients irrespectively of treatment option. Whether long-term cardiovascular risk is dependent on lipid profile, diabetes, obesity or GAGs deposition within the organ system remains unanswered.

Introduction: Mucopolysaccharidosis (MPS) type IVA is a rare, autosomal recessive lysosomal storage disease causing substrate accumulation in various organs and tissues. MPS IVA is associated with both obstructive and restrictive airway disease, with the former often resulting in sleep disordered breathing (SDB). Respiratory failure is a primary cause of death in this condition. The aim of this study was to characterise and catalogue the long-term respiratory changes in patients with MPS IVA treated with, or without, enzyme replacement therapy (ERT). Methods: In this retrospective, longitudinal, repeated-measures cohort study, descriptive statistics and non-parametric correlation were performed for demographic, respiratory function and oximetry variables over a study period from January 2009 to December 2018. Composite clinical endpoints used in this study for evaluating pulmonary function included spirometry variables (FEV1, FEV1 [%Pred] FVC, FVC [%Pred] and FEV1/FVC), oximetry variables (median %Spo2, ODI 3%, mean nadir 3%, ODI 4%, mean nadir 4% and min dip SpO2 [%]) and 6MWT to assess functional exercise capacity and thus integrated cardiopulmonary function. Results: Sequential spirometry and oximetry values were collected from 16 patients, of which 13/16 were ERT treated. In general, during the study period there was a global reduction in static spirometry values in all subjects, as well as cardiorespiratory function as assessed by the 6MWT, with the decline being delayed in the ERT group. Oximetry changed to a minor degree over time in the ERT group, whereas it declined in the non-ERT group. FEV1, FVC [%predicted] and ODI 3% exhibited a strong, combined positive correlation (r 0.74–95% CI 0.61 to 0.83; p

Patients with mucopolysaccharidoses (MPS) frequently require anaesthesia for diagnostic or surgical interventions and thereby experience high morbidity. This study aimed to develop a multivariable prediction model for anaesthesia-related complications in MPS. This two-centred study was performed by retrospective chart review of children and adults with MPS undergoing anaesthesia from 2002 until 2018. We retrieved the patients’ demographics, medical history, clinical manifestations, and indication by each anaesthesia. Multivariable mixed-effects logistic regression was calculated for a clinical model based on preoperative predictors preselected by lasso regression and another model based on disease subtypes only. Of the 484 anaesthesia cases in 99 patients, 22.7% experienced at least one adverse event. The clinical model resulted in a better forecast performance than the subtype-model (AICc 460.4 vs. 467.7). The most relevant predictors were hepatosplenomegaly (OR 3.10, CI 1.54–6.26), immobility (OR 3.80, CI 0.98–14.73), and planned major surgery (OR 6.64, CI 2.25–19.55), while disease-specific therapies, i.e., haematopoietic stem cell transplantation (OR 0.45, CI 0.20–1.03), produced a protective effect. Anaesthetic complications can best be predicted by surrogates for advanced disease stages and protective therapeutic factors. Further model validation in different cohorts is needed.

PURPOSE This study was conducted to determine 1) the concentration of hyaluronan (HA) in the tear films of contact lens (CL) wearers versus non-CL wearers and 2) whether HA sorbed from Biotrue, an HA-containing multipurpose solution (MPS), onto senofilcon A lenses affects the concentration of HA in tears after 2 hours of wear. PATIENTS AND METHODS Tears of habitual CL wearers and non-CL wearers were collected on Schirmer strips at baseline and after 2 hours of wear of senofilcon A CLs that had first been either rinsed with Sensitive Eyes Saline or soaked in Biotrue MPS for 14 hours. HA concentrations were measured by enzyme-linked immunosorbent assay (ELISA) and adjusted for sample volumes. RESULTS No difference in baseline concentrations of HA in tears was found between CL wearers and non-CL wearers (P=0.07), nor between males and females (P=0.06). However, age was significantly negatively associated with HA concentration (P

In spectral-spatial classification of hyperspectral image tasks, the performance of conventional morphological profiles (MPs) that use a sequence of structural elements (SEs) with predefined sizes and shapes could be limited by mismatching all the sizes and shapes of real-world objects in an image. To overcome such limitation, this paper proposes the use of object-guided morphological profiles (OMPs) by adopting multiresolution segmentation (MRS)-based objects as SEs for morphological closing and opening by geodesic reconstruction. Additionally, the ExtraTrees, bagging, adaptive boosting (AdaBoost), and MultiBoost ensemble versions of the extremely randomized decision trees (ERDTs) are introduced and comparatively investigated for spectral-spatial classification of hyperspectral images. Two hyperspectral benchmark images are used to validate the proposed approaches in terms of classification accuracy. The experimental results confirm the effectiveness of the proposed spatial feature extractors and ensemble classifiers.

Objectives: As the feasibility of obtaining health care has improved in the last decade, there is an increase in the number of performing unnecessary coronary angiogram. Red Cell Distribution Width (RDW), which shows erythrocyte dispersion volume, is associated with coronary artery disease. The present study aims to evaluate the relationship between RDW value and the severity of coronary artery disease in patients who undergo myocardial perfusion scintigraphy (MPS) as an evaluation for coronary ischemia and after which patients had a coronary angiography. Methods: This retrospective study included 452 patients diagnosed as stabile angina that had MPS to evaluate coronary ischemia and after which coronary angiography was performed. Complete blood count was obtained on the same day. Patients were first divided into two groups: patients with and without ischemia on MPS. Then, the group who had ischemia on the MPS where divided into another two groups: patients who had RDW values ≥13.5 and the others who had RDW value

Mucopolysaccharidoses (MPS) constitute a heterogeneous group of rare genetic disorders caused by enzymatic deficiencies that lead to the accumulation of glycosaminoglycans (GAGs). Clinical observations suggest a health-related impairment in quality of life in patients with MPS. Professionals with extensive experience in the care of patients with inborn errors of metabolism, such as MPS, held a meeting in April 2017 to discuss and propose recommendations for the evaluation and management of quality of life in MPS patients in Latin America. In the light of this scenario, the present work summarizes the content of the discussions and presents the recommendations produced at the meeting. The panel had suggested the use of the following tools for the assessment of health-related quality of life (HRQoL): Children's Health Assessment Questionnaire (CHAQ) for children and patients unable to express their feelings, Health Assessments Questionnaire (HAQ) and EuroQol 5 Domains (EQ-5D) scales for adult patients. Based on the scores verified in these scales, the panel proposes interventions that aim reducing the impairment of the quality of life in patients with MPS disorders.

This paper explores the demand for performance information by members of the Croatian Parliament, and the supply thereof by the Croatian public administration. The research consists of data content analysis of parliamentary questions and answers in the first six months of 2015. The results show that the demand for performance information by MPs is lower than its supply by the administration. The MPs’ personal characteristics have an influence on the demand for performance information since higher demand is shown by those belonging to opposition parties, while those most experienced politically are the ones requesting least information. The influence of MPs’ education on the demand for performance information is not unequivocal. Two issues are further discussed: development of the performance management system and an increase in the power of executives, which can be a result of the Europeanization process.

In very high resolution (VHR) remote sensing (RS) classification tasks, conventional pixel-based contextual information extraction methods such as morphological profiles (MPs), extended MPs (EMPs) and MPs with partial reconstruction (MPPR) with limited numbers, sizes and shapes of structural elements (SEs) cannot perfectly match all sizes and shapes of the objects in an image. To overcome such limitation, we introduce novel spatial feature extractors, namely, the superpixel-guided morphological profiles (SPMPs), where the superpixels are used as SEs in opening by reconstruction and closing by reconstruction operations. Moreover, to avoid possible side effects from unusual maximum and minimum values within superpixels, the mean pixel value of superpixels is adopted (SPMPsM). Additionally, new decision forest based on penalizing the attributes in previous trees, the ForestPA is introduced and evaluated through a comparative investigation on three VHR multi-/hyperspectral RS image classification tasks. Support vector machine and benchmark ensemble classifiers, including bagging, AdaBoost, MultiBoost, ExtraTrees, Random Forest and Rotation Forest, are adopted. The experimental results confirm the effectiveness and superior performances of the proposed SPMPs and SPMPsM relative to those of the MPs and MPPR. Moreover, ForestPA outperforms only bagging and is not suitable for learning from large numbers of samples with high dimensionality from the computational efficiency and classification accuracy perspective.

The aim of this review is to summarize the evidence on efficacy, effectiveness and safety of intravenous enzyme replacement therapy (ERT) available for mucopolysaccharidoses (MPSs) I, II, IVA, VI and VII, gained in phase III clinical trials and in observational post-approval studies. Post-marketing data are sometimes conflicting or controversial, possibly depending on disease severity, differently involved organs, age at starting treatment, and development of anti-drug antibodies (ADAs). There is general agreement that ERT is effective in reducing urinary glycosaminoglycans and liver and spleen volume, while heart and joints outcomes are variable in different studies. Effectiveness on cardiac valves, trachea and bronchi, hearing and eyes is definitely poor, probably due to limited penetration in the specific tissues. ERT does not cross the blood–brain barrier, with the consequence that the central nervous system is not cured by intravenously injected ERT. All patients develop ADAs but their role in ERT tolerance and effectiveness has not been well defined yet. Lack of reliable biomarkers contributes to the uncertainties about effectiveness. The data obtained from affected siblings strongly indicates the need of neonatal screening for treatable MPSs. Currently, other treatments are under evaluation and will surely help improve the prognosis of MPS patients.

Mucopolysaccharidoses (MPS) are a group of rare lysosomal storage disorders characterized by the accumulation of glycosaminoglycans (GAGs) in different parts of the eye. Ocular problems are very common in MPS children, and the cornea, sclera, trabecular meshwork, retina, and optic nerve may all be involved. Early diagnosis is very important to preserve the visual function, and the diagnosis requires experience and different evaluations. Follow-up is mandatory to allow a correct pathway to consequent therapy. This article aims to provide a review of ocular alterations and treatment options in MPS. The ophthalmologist is sometimes the first physician who can suspect a metabolic disease and can help to make the correct diagnosis. It is important to stimulate awareness of MPS among ophthalmologists.

Mucopolysaccharidoses (MPS) comprise a group of lysosomal disorders that are characterized by progressive, systemic clinical manifestations and a coarse phenotype. The different types, having clinical, biochemical, and genetic heterogeneity, share key clinical features in varying combinations, including joint and skeletal dysplasia, coarse facial features, corneal clouding, inguinal or abdominal hernias, recurrent upper respiratory tract infections, heart valve disease, carpal tunnel syndrome, and variable neurological involvement. In the severe forms, these features usually appear in the first months of life, but a correct diagnosis is often reached later when suggestive signs are manifest. All MPS types may have severe or attenuated presentations depending on the residual enzymatic activity of the patient. Based on data from the literature and from personal experience, here we underline the very early signs of the severe forms which should alert the paediatrician on their first appearance. A few early signs are typical of MPS (i.e. gibbus) while many are unspecific (hernias, upper airway infections, organomegaly, etc.), and finding the association of many unspecific signs might prompt the paediatrician to search for a common cause and to carefully look for other more specific signs (gibbus and other skeletal deformities, heart murmur). We stress the need to increase awareness of MPS among paediatricians and other specialists to shorten the still existing diagnostic delay. A timely diagnosis is mandatory for the commencement of treatment as soon as possible, when available, to possibly obtain better results.

International audience; Developing nanoparticles to improve the specificity of anticancer agents towards tumor tissues and to better control drug delivery is a rising strategy in oncology. An increasing number of forms (e.g., conjugated nanoparticles, liposomes, immunoliposomes…) are now made available on the shelves and numerous other scaffolds (e.g., dendrimeres, nanospheres, squalenes…) are currently at various stages of development. However, the attrition rate when developing nanoparticles is particularly high and several promising forms showing excellent behavior and efficacy in preclinical studies failed to succeed in subsequent first-in-man studies or later in phase-II trials. The issue of pharmacokinetic variability is a major, yet largely underestimated issue with nanoparticles. A wide variety of causes (e.g; tumor type and disease staging, comorbidities, patient’s immune system) can explain this variability, which can in return impact negatively on pharmacodynamic endpoints such as lack of efficacy or severe toxicities. This review aims at covering the main causes for erratic pharmacokinetics observed with most nanoparticles. Should the main causes of such variability be identified, specific studies in non-clinical or clinical development stages could be undertaken using dedicated models (i.e., mechanistic or semi-mechanistic mathematical models such as PBPK approaches) to better describe nanoparticles pharmacokinetics and decipher PK/PD relationships. In addition, identifying relevant biomarkers or parameters likely to impact on nanoparticles pharmacokinetics would allow either modifying their characteristics to reduce the influence of the expected variability during development phases, or developing biomarker-based adaptive dosing strategies to maintain an optimal efficacy/toxicity balance. Overall, we call of developing comprehensive distribution studies and state-of-the-art modeling support to help better picture and anticipate nanoparticles pharmacokinetics.

The objective of this research is to develop a Master Production Scheduling (MPS) model to maximize the total profit using Mixed Integer Linear Programming (MILP). The model is solved using both MILP with the Xpress software and genetic algorithms with the Evolver solver. The model is built for Evolver in MS Excel. Results of both solving tools are compared to analyze the performance of each of them. The accuracy and capability of the model to solve the MPS problems have been verified through the discussion of its results logicality for different cases of different patterns.

Over-the-air multi-probe setups provide an efficient way to characterize the performance of today’s advanced wireless communication systems. In this paper the measurement uncertainty of such a setup using a car as a test object is characterized through three experiments: measurement system analysis, channel sounder measurements, and probe coupling measurements. Four issues were in focus for the analysis; precision, realization of the wireless communication channel, coupling between the probes, and the influence of the test object size. The analysis shows that a large test object such as a car in an over-the-air multi-probe ring will affect the measurement uncertainty, but only to a small degree. The measurement uncertainty expressed as expanded uncertainty was below +/-1dB, a level that would not violate best practice total uncertainty levels for comparable over-the-air methods.

The mucopolysaccharidoses (MPS) are a group of lysosomal storage disorders caused by inborn errors of glycosaminoglycan (GAG) metabolism. These diseases are classified by enzyme deficiency into seven groups: type I, II, III, IV, VI, VII, and IX. GAG accumulation leads to characteristic clinical features. Some ophthalmic findings that are characteristic of MPS diseases include corneal clouding, retinal degeneration, decreased electroretinogram wave amplitude, optic atrophy, papilledema, and glaucoma. Current treatments such as hematopoietic stem cell transplantation and enzyme replacement therapy have increased the life span of many MPS patients and created the need to improve management of ocular symptoms. This article aims to provide a comprehensive review of ocular manifestations and treatment options for the various types of MPS.

This study of political communication in France and Germany offers a detailed analysis of citizens’ as well as representatives’ behavior in several political communication situations (interpersonal, mediated by the mass media, online). By comparing MPs’ strategies of top-down political communication with citizens’ tendencies to get political information from traditional media sources, the authors observe a dichotomy in communication styles. A communication gap results from MPs shifting efforts to online channels while citizens continue their reliance on traditional mass media.

Mucopolysaccharidoses type IVA (Morquio disease) is a rare, autosomal recessive lysosomal storage disease that causes both obstructive and restrictive airway pathology, with respiratory failure being the primary cause of death. This article provides original data on the longitudinal characterization of pulmonary function changes in children with Mucopolysaccharidoses (MPS) IVA by presenting the data and nuanced trends of changes from sequential spirometry and oximetry. The sample size included 16 subjects, 13 had undergone enzyme replacement therapy (ERT), three had not undergone ERT treatment. A total of 180 individual plots are presented for spirometry variables (FEV1, FEV1 [%Pred] FVC, FVC [%Pred] and FEV1/FVC), 6MWT and oximetry variables (median %Spo2, ODI 3%, mean nadir 3%, ODI 4%, mean nadir 4% and min dip SpO2 [%]); over a nine-year period at a single quaternary paediatric metabolic centre. This data has been made public and has utility to clinicians and researchers due to the following: [1,2] by providing the first comprehensive report of detailed changes in pulmonary function in children with MPS IVA, with and without ERT; [1–3] as well as changes in pulmonary function following the institution of non-invasive ventilation (NIV) and adenotonsillectomy. The data presented is related to the research article by Kenth et al. “The Characterization of Pulmonary Function in Patients with Mucopolysaccharidoses IVA: A Longitudinal Analysis”. Keywords: Morquio syndrome, Mucopolysaccharidosis IVA, MPS, Respiratory changes, Enzyme replacement therapy, Sleep-disordered breathing

Objective Mucopolysaccharidosis IVA (MPS IVA, or Morquio A syndrome) and VI (MPS VI, or Maroteaux–Lamy syndrome) are autosomal recessive lysosomal storage disorders. Skeletal abnormalities are common initial presenting symptoms and, when recognized early, may facilitate timely diagnosis and intervention, leading to improved patient outcomes. Patients with slowly progressing disease and nonclassic phenotypes can be particularly challenging to diagnose. The objective was to describe the radiographic features of patients with a delayed diagnosis of MPS IVA or VI. Materials and Methods This was a retrospective study. The records of 5 MPS IVA and 3 MPS VI patients with delayed diagnosis were reviewed. Radiographs were evaluated by a radiologist with special expertise in skeletal dysplasias. Results An important common theme in these cases was the appearance of multiple epiphyseal dysplasia (MED) with epiphyseal changes seemingly confined to the capital (proximal) femoral epiphyses. Very few patients had the skeletal features of classical dysostosis multiplex. Conclusions Radiologists should appreciate the wide phenotypic variability of MPS IVA and VI. The cases presented here illustrate the importance of considering MPS in the differential diagnosis of certain skeletal dysplasias/disorders, including MED, some forms of spondylo-epiphyseal dysplasia (SED), and bilateral Perthes-like disease. It is important to combine radiographic findings with clinical information to facilitate early testing and accurate diagnosis.

The mucopolysaccharidoses (MPS disorders) are rare inherited diseases associated with multi-organ accumulation of glycosaminoglycans, leading to musculoskeletal, respiratory, cardiac, neurological, ophthalmological, otolaryngological, and gastrointestinal abnormalities. As a result of improvements in diagnosis, multi-disciplinary care, and therapies such as enzyme replacement therapy and hematopoietic stem cell transplantation, an increasing number of patients with MPS are reaching adulthood and are involved in family planning. Data on fertility and pregnancy outcome in MPS is sparse and comprises primarily isolated case reports. To address this evidence gap, we present a case series on fertility and pregnancy in eight mothers and five fathers with MPS. This case series demonstrates that women with MPS have high-risk pregnancies and deliveries secondary to their underlying disease. However, with appropriate pre-conceptual multi-disciplinary evaluation, optimization and discussion regarding potential risks, combined with regular multi-disciplinary maternal and fetal surveillance in a tertiary center, the outcome of most pregnancies in this case series seems to be favorable with all babies developing normally. Partners of fathers with MPS had uncomplicated pregnancies and deliveries. All children were healthy, with normal growth and development.

Katarzyna A Wygladacz, Daniel J Hook Vision Care, Bausch & Lomb Incorporated, Rochester, NY, USA Abstract: Biotrue multipurpose solution (MPS) is a bioinspired disinfecting and conditioning solution that includes hyaluronic acid (HA) as a natural wetting agent. Previous studies demonstrated that HA sorbed from Biotrue MPS on both conventional and silicone hydrogel (SiHy) contact lens materials; an in vitro simulated-wear test validated the presence of HA on the lens surfaces for as long as 20 hours. In this study, the morphology and distribution of HA sorbed from both Biotrue and pure HA solution on SiHy contact lens surfaces was examined. Atomic force microscopy imaging was used to illustrate the topography of fresh SiHy contact lens materials before and after incubation with 0.1% (w/v) HA solution. The distribution, as well as fine details of the HA network, were resolved by first staining HA with Gram’s safranin, then imaging with confocal laser-scanning microscopy and differential interference-contrast microscopy. In this approach, SiHy materials take up the dye (safranin) nonspecifically, such that the resultant safranin–HA complex appears dim against the fluorescent lens background. Balafilcon A was chosen as the representative of glassy SiHy lenses that require postpolymerization plasma treatment to increase wettability. Senofilcon A and samfilcon A were chosen as representatives of SiHy materials fabricated with an internal wetting agent. A confluent and dim HA–safranin network was observed adhered to balafilcon A, senofilcon A, and samfilcon A lens surfaces incubated with either 0.1% (w/v) HA solution or Biotrue MPS. Therefore, the conditioning function provided by Biotrue MPS may be in part explained by the presence of the HA humectant layer that readily sorbs on the various types of SiHy contact lens materials. Keywords: contact lens, hyaluronan, MPS, AFM, CLSM, DIC microscopy

Background: The presence of severe hypokinesia or akinesia and near complete stenotic lesions on coronary angiography, in a patient with acute myocardial infarction raises a question of viability in the involved territory and its response to revascularization. The decision of revascularization can be effectively taken after myocardial perfusion scintigraphy (MPS). Aim: To evaluate the role of MPS in patients with acute or recent myocardial infarction after invasive coronary angiography. Materials and Methods: Thirty-five patients (27 Males, 8 Females; Mean age 54 years) with acute myocardial infarction, who underwent invasive angiography, were included prospectively. Invasive angiography was attempted during the episode of acute chest pain in 20 patients. Fifteen patients underwent angiography without MPS because of non-availability of MPS at the time of initial presentation in the referring hospital. Revascularization was deferred because of complete / near complete block of artery with hypokinesia / akinesia of the distal LV segments in 32 / 35 patients and 50 to 70% block in 3 / 35. These patients were subjected to MPS. Results: Twenty patients underwent stress MPS and 15 underwent nitrate-augmented rest re-distribution study (RR study). Imaging was performed using the hybrid SPECT / CT system. The average defect size of the perfusion defect was 34% (5 - 57% range). Sixteen patients (46%) had fixed perfusion defects. Reversible ischemia was present in 19 (54%). Ten patients had a < 10% reversible perfusion defect. Nine patients had reversible ischemia, > 10% of the LV myocardium, and underwent the invasive revascularization procedure. Conclusion: MPS is invaluable in patients who have total / near total occlusion of the coronary artery and distal segment hypokinesia or akinesia on invasive angiography. One in four patients, deemed to have non-viable myocardium, underwent an invasive revascularization after undergoing MPS.

WOS: 000377110800007, PubMed ID: 26908836, Background Mucopolysaccharidosis VII (MPS VII) is an ultra-rare disease characterised by the deficiency of beta-glucuronidase (GUS). Patients' phenotypes vary from severe forms with hydrops fetalis, skeletal dysplasia and mental retardation to milder forms with fewer manifestations and mild skeletal abnormalities. Accurate assessments on the frequency and clinical characteristics of the disease have been scarce. The aim of this study was to collect such data. Methods We have conducted a survey of physicians to document the medical history of patients with MPS VII. The survey included anonymous information on patient demographics, family history, mode of diagnosis, age of onset, signs and symptoms, severity, management, clinical features and natural progression of the disease. Results We collected information on 56 patients from 11 countries. Patients with MPS VII were classified based on their phenotype into three different groups: (1) neonatal non-immune hydrops fetalis (NIHF) (n=10), (2) Infantile or adolescent form with history of hydrops fetalis (n=13) and (3) Infantile or adolescent form without known hydrops fetalis (n=33). Thirteen patients with MPS VII who had the infantile form with history of hydrops fetalis and survived childhood, had a wide range of clinical manifestations from mild to severe. Five patients underwent bone marrow transplantation and one patient underwent enzyme replacement therapy with recombinant human GUS. Conclusions MPS VII is a pan-ethnic inherited lysosomal storage disease with considerable phenotypical heterogeneity. Most patients have short stature, skeletal dysplasia, hepatosplenomegaly, hernias, cardiac involvement, pulmonary insufficiency and cognitive impairment. In these respects it resembles MPS I and MPS II. In MPS VII, however, one unique and distinguishing clinical feature is the unexpectedly high proportion of patients (41%) that had a history of NIHF. Presence of NIHF does not, by itself, predict the eventual severity of the clinical course, if the patient survives infancy., Ultragenyx Pharmaceutical [16232], This work was supported in part by Ultragenyx Pharmaceutical grant number 16232.

The edge of the RFX-mod (R=2m, a=0.46m) Reversed Field Pinch device is characterized by weak magnetic chaos affecting ion and electron diffusion. Edge particle transport is strongly influenced by a toroidal asymmetry caused by magnetic islands and an ambipolar radial electric field ensures local neutrality, in a way similar to the stochastic edge of tokamaks when resonant magnetic perturbations (RMPs) are applied. The H? emission and floating potential Vf measured in different poloidal and toroidal positions shows a helical shape of the Plasma Wall Interaction, fitting the spatial periodicity of the innermost resonant tearing mode (m/n=1/7) [1]. However, detailed measurements, along the poloidal (parallel) direction, of the electron density and temperature with the Thermal Helium Beam, and of the floating potential Vf with electrostatic probes, show that the response of the edge plasma depends on the poloidal angle, in a more complicated way than a pure 1/7 harmonic. In particular, multiple poloidal harmonics can be recognized in the measurements. The results are robust, because data analysis has been performed with different techniques: in terms of correlations between Vf signals and the corresponding local flux-surface displacement, by the conditional average technique applied at Vf signals, and finally also in terms of a travelling helical angle frame as reference of the measurements. The interpretation of the results is not obvious, but it highlights the fact that the correlation between magnetic islands and kinetic properties of the edge plasma is not a simple one-to-one causal relationship, as it is often assumed in RMP studies in tokamaks.

For realistic turbulent flow simulations, quantitative representation of turbulent flow dynamics is desired. In the present study, two-dimensional homogeneous isotropic turbulence is simulated by using a grid-free vortex method to focus on the viscous dissipation process. The results are compared with those of spectral DNS. Two viscous diffusion models, i.e., a core spreading model and Moving Particle Semi-implicit (MPS) Laplacian model, are compared. For the former model, merging and insertion of particles are incorporated to ensure uniform distribution of vortex elements. It is shown that the MPS Laplacian model is superior to the conventional core spreading model in terms of the decay rate of enstrophy and energy spectra. Furthermore, the computational time is remarkably reduced by using a Fast Multipole Method (FMM), while retaining accuracy.

Introduction: Of the 762 public hospitals in Australia, 71% have less than fifty beds. These smaller hospitals, in most cases, were built decades ago and little or no attempt has been made to redesign them. There is little, if any, research or studies into their operation, mostly no plans for their future and how they could become hubs for integrated care. There is however an exception to this. This presentation describes this exception and how this knowledge was derived. Method: This doctoral research investigated the role of the smaller public hospitals to contribute to a better understanding of factors driving change in rural hospitals and characteristics that assist them to be viable and sustainable. A sample of 25 small rural hospitals, of different sizes and throughputs, were examined in detail through quantitative analysis of retrospective data over an eleven year period. The response of these facilities to their catchment populations’ needs were examined in detail for a range of factors. As part of the study an instrument the Hospital Supply Index (HSI) was developed to measure whether a public hospital was responding to the contemporary healthcare needs of its catchment population and was likely to be sustainable into the future. Results: Among the hospitals examined, one group stood out. These were called Multi-Purpose Services (MPS). In these facilities the entire service: aged care; in-hospital care; out of hospital care; primary health care; and social services are integrated and work ‘as one’. Discussion: Out of the sample of 25 hospitals in the study, the six MPSs were ‘different’. These hospitals had reinvented themselves and were the exceptions to the trend. The index showed they were sustainable services, responding to the needs of the population (HSI of >40) and the community relied heavily on their services. The care provided by these facilities was significantly different to other hospitals of similar size. On investigation it was found that these MPS hospitals had certain characteristics that made them different. These primarily related to integration. The facilities had co-located the care the patients needed on one site. They had: a single management structure for all elements of care (inpatient hospital care, aged care, outpatient community care, and social services); they had a single budget; the management was able to move resources to follow the patient’s needs; the workforce worked closely together, met regularly and collaborated; the care of the patient came first; and there were structures and organisational arrangements to support patient-centred care. International Journal of Integrated Care – Volume 15, 17 Nov – URN:NBN:NL:UI:10-1-117319 – http://www.ijic.org 3 rd World Congress on Integrated Care, Mexico City, Mexico, 19-21 November, 2015 Conclusion: There are certain characteristics that make MPSs different form the historical rural hospital structure and facilitate provision of integrated care to the community. It could be said that the integration characteristics of these hospitals have allowed them to be successful and sustainable in contrast to their peers that have not embraced change and are frequently ‘bypassed’ by local residents and are losing services. There is much that can be learned from the transformation the MPS facilities have gone through and their characteristics. Conference abstract Spanish Introduccion: De los 762 hospitales publicos que hay en Australia, el 71% tiene menos de cincuenta camas. Estos hospitales mas pequenos, en la mayoria de los casos, fueron construidos hace decadas y pocos o ninguno ha hecho un intento para redisenarlos. Hay poca o ninguna investigacion o estudios sobre su funcionamiento, y en su mayoria no hay planes para su futuro ni forma en que podrian convertirse en centros de atencion integral. Sin embargo, existe una excepcion a esto. Esta presentacion describe esta excepcion y como se obtuvo ese conocimiento. Metodo: Esta investigacion doctoral investigo el papel de los hospitales publicos mas pequenos para contribuir a una mejor comprension de los factores de cambio en los hospitales rurales y las caracteristicas que les ayuden a ser viable y sostenible su conduccion. Una muestra de 25 pequenos hospitales rurales, de diferentes tamanos y rendimientos, se examinaron en detalle a traves del analisis cuantitativo de los datos retrospectivos en un periodo de once anos. La respuesta de estas instalaciones a las necesidades de la poblacionque atienden 'fue examinada en detalle para una serie de factores. Como parte del estudio de un instrumento el indice de alimentacion del Hospital (HSI) fue desarrollado para medir si un hospital publico estaba respondiendo a las necesidades de salud actuales de su poblacion atendida y su probabilidad de ser sostenible en el futuro. Resultados: Entre los hospitales analizados, un grupo se destaco, estos fueron llamados Servicios Multi-Propositos (MPS). En estas instalaciones se brindan todos los servicios: cuidado de ancianos; cuidados dentro del hospital; atencion hospitalaria externa; primeros auxilios; y servicios sociales son integrados y trabajan "como uno". Discusion: De la muestra de 25 hospitales en el estudio, los seis MPS eran "diferentes". Estos hospitales se han reinventado a si mismos y la tendencia eran las excepciones. El indice mostro que eran servicios sostenibles, respondiendo a las necesidades de la poblacion (HSI de> 40) y a la comunidad basados en gran medida en sus servicios. La atencion recibida por estas instalaciones fue significativamente diferente a otros hospitales de tamano similar. En la investigacion se encontro que estos hospitales de MPS tenian ciertas caracteristicas que los hacian diferentes. Estas principalmente relacionadas con la integracion. Las instalaciones habian co-localizado el cuidado de los pacientes en un sitio necesario. Tenian: una unica estructura de gestion para todos los elementos de la atencion (atencion hospitalaria, cuidado de ancianos, cuidado de la comunidad ambulatoria, y servicios sociales); tenian un presupuesto unico; la gestion fue capaz de mover los recursos para seguir las necesidades del paciente; la poblacion activa trabajaba en estrecha colaboracion, se reunio periodicamente y colaboro; con el cuidado del paciente en orden de llegada; y habia estructuras y arreglos de organizacion para apoyar la atencion centrada en el paciente. Conclusion: Hay ciertas caracteristicas que hacen que los MPS formen una diferente estructura de hospital rural historico y faciliten la prestacion de atencion integrada a la comunidad. Se podria decir que las caracteristicas de integracion de estos hospitales han permitido que sean exitosos y sostenibles en contraste con sus similaes que no han adoptado el cambio y son con frecuencia "anulados" por los residentes locales y estan perdiendo servicios. Es mucho lo que se puede aprender de la transformacion de las instalaciones de los MPS han atravesado y sus caracteristicas.

Routine use of massively parallel sequencing (MPS) for forensic genomics is on the horizon. The last few years, several algorithms and workflows have been developed to analyze forensic MPS data. However, none have yet been tailored to the needs of the forensic analyst who does not possess an extensive bioinformatics background.We developed our previously published forensic MPS data analysis framework MyFLq (My-Forensic-Loci-queries) into an open-source, user-friendly, web-based application. It can be installed as a standalone web application, or run directly from the Illumina BaseSpace environment. In the former, laboratories can keep their data on-site, while in the latter, data from forensic samples that are sequenced on an Illumina sequencer can be uploaded to Basespace during acquisition, and can subsequently be analyzed using the published MyFLq BaseSpace application. Additional features were implemented such as an interactive graphical report of the results, an interactive threshold selection bar, and an allele length-based analysis in addition to the sequenced-based analysis.Practical use of the application is demonstrated through the analysis of four 16-plex short tandem repeat (STR) samples, showing the complementarity between the sequence- and length-based analysis of the same MPS data.

Over the last decade, significant progress has been made in the field of drug delivery. The advent of engineered nanoparticles has allowed us to circumvent the initial limitations to drug delivery such as pharmacokinetics and solubility. However, in spite of significant advances to tumor targeting, an effective treatment strategy for malignant tumors still remains elusive. Tumors possess distinct physiological features which allow them to resist traditional treatment approaches. This combined with the complexity of the biological system presents significant hurdles to the site-specific delivery of therapeutic drugs. One of the key features of engineered nanoparticles is that these can be tailored to execute specific functions. With this review, we hope to provide the reader with a clear understanding and knowledge of biological barriers and the methods to exploit these characteristics to design multifunctional nanocarriers, effect useful dosing regimens and subsequently improve therapeutic outcomes in the clinic.

[Purpose] The present study examined the effects of treatment using PNF extension techniques on the pain, pressure pain, and neck and shoulder functions of the upper trapezius muscles of myofascial pain syndrome (MPS) patients. [Subjects] Thirty-two patients with MPS in the upper trapezius muscle were divided into two groups: a PNF group (n=16), and a control group (n=16) [Methods] The PNF group received upper trapezius muscle relaxation therapy and shoulder joint stabilizing exercises. Subjects in the control group received only the general physical therapies for the upper trapezius muscles. Subjects were measured for pain on a visual analog scale (VAS), pressure pain threshold (PPT), the neck disability index (NDI), and the Constant-Murley scale (CMS). [Results] None of the VAS, PPT, and NDI results showed significant differences between the groups, while performing postures, internal rotation, and external rotation among the CMS items showed significant differences between the groups. [Conclusion] Exercise programs that apply PNF techniques can be said to be effective at improving the function of MPS patients.

This paper explores some causes and the consequences of constituency service in a proportional representational system. Turkey provides an interesting case here. First, its province-size constituencies generate a significant size of personal votes for a candidate, though nominated in the party list. Second, as in other non-western democracies, it is the service and allocational aspects of responsiveness that compose the most frequent demands from constituents to parliamentarians in Turkey. There exists, however, conflicting evidence regarding what priority Turkish parliamentarians give to constituency service. The analysis of the data collected through a questionnaire survey highlights several features of constituency service in Turkey. First, in terms of daily activities, parliamentarians spend for constituency service the largest part of their time at their own disposal. Second, for reelection purposes, parliamentarians consider their individual activities to be almost as important as party popularity. Third, the demand for and supply of constituency service depend on different politico-economic structures of the constituency. The smaller the constituency size, the larger will be the demand for and the supply of constituency service. The economically less developed constituencies tend to generate more demand than the more developed constituencies but do not significantly motivate the parliamentarians to provide constituency service. In addition, the Turkish parliamentarian’s turnover rate is much higher than in other democratic countries. Therefore even reelected parliamentarians have to take constituency service seriously. The statistical test shows no significant difference in the practices of constituency service between newly-elected and reelected parliamentarians.

The Modular Production System (MPS) can be used to reproduce nearly any function in complex manufacturing processes. In this work a different way of real time TCP/IP control of three different MPS controlled by embedded processors inside a FPGA is proposed. The digital design with FPGA is particularly advantageous due to its parallel processing made possible by its flexible structure, high integration and velocity. The TCP/IP control is carried out with a Rabbit Core microprocessor. This device contains the functions required to implement a web server allowing the remote control of the MPS. A user enters a public IP direction on a designed web page to enable/disable each independent manufacturing process.

Dual left anterior descending artery (LAD) is a rare variation in the coronary artery anatomy having 4 different subtypes. We report a rare scenario of type IV dual LAD, with short LAD critical stenosis, compensated by a long LAD perfusing the same territory, which was missed on initial angiographic evaluation. Myocardial perfusion scan (MPS) of this patient showed preserved perfusion. A review of angiogram revealed this anomaly, indicating that a meticulous correlation of anatomic and functional modalities is necessary as it could change further management of patient.