A tomographic spatial-unfolding method for Compton gamma imaging measurements.

An advanced spatial-unfolding technique capable of reconstructing the activity distribution within an exclusion zone from Compton gamma imager measurements taken outside of it is introduced. Although the method is generally applicable to extended sources, we demonstrate it here on a calibrated Cs-137 point source through Monte Carlo simulation studies as well as with measurements made using a Silicon Compton Telescope for Safety and Security (SCoTSS) gamma imager. For synthetic data the method accurately reconstructs the total activity contained within the mapped zone of interest, even when the size of the basis elements used to reconstruct the activity distribution is larger than the source itself.

A national pilot of donation after circulatory death (DCD) heart transplantation within the United Kingdom.

Background: The United Kingdom (UK) was one of the first countries to pioneer heart transplantation from donation after circulatory death (DCD) donors. To facilitate equity of access to DCD hearts by all UK heart transplant centers and expand the retrieval zone nationwide, a Joint Innovation Fund (JIF) pilot was provided by NHS Blood and Transplant (NHSBT) and NHS England (NHSE). The activity and outcomes of this national DCD heart pilot program are reported.

Tomographic reconstruction of a spatially-extended source from the perimeter of a restricted-access zone using a SCoTSS compton gamma imager.

It is a standard procedure in many countries that response to a nuclear or radiological accident or incident would involve mobile aerial- or ground-based survey with highly sensitive gamma-ray detectors to map the distribution of radioactivity. There may however arise situations in which ground- or air-based detectors are not able to access an area to survey for radioactive materials, therefore technologies and techniques that can estimate the position and activity of radioactive materials from a distance are under development. Tomographic reconstruction methods, well-known in medical physics, permit the reconstruction of an N-dimensional map or image, from a number of N-1-dimensional cross-sectional images, or back-projections.

Revision of the Nearctic genus Tritoxa Loew (Diptera: Ulidiidae).

The species of the Nearctic genus Tritoxa Loew are revised. Seven species of Tritoxa are recognized, including two new species: T. californica sp.

Discovery of ONO-8590580: A novel, potent and selective GABA α negative allosteric modulator for the treatment of cognitive disorders.

The identification and SAR development of a series of negative allosteric modulators of the GABA α5 receptor is described. This novel series of compounds was optimised to provide analogues with high GABA α5 binding affinity, high α5 negative allosteric modulatory activity, good functional subtype selectivity and low microsomal turnover, culminating in identification of ONO-8590580.

myHip&Knee: Improving Patient Engagement and Self-Management Through Mobile Technology.

Given the increasing volume of hip and knee replacement surgery with reduced hospital stays and resources, we explored technology to address gaps in patient care and enhance self-management. The team at the Holland Orthopaedic and Arthritic Centre of Sunnybrook Health Sciences Centre, which performs a high volume of joint replacement surgery, partnered with patients and a health technology company to create a mobile app: myHip&Knee. The results to date demonstrate that the app improves patient experience and reduces follow-up calls to surgeons' offices, ultimately reducing demand on healthcare resources.

Proliferative Cartilaginous Lesions in the Calcaneal Tendons of huNOG Mice.

NOD/Shi-scid/IL-2Rγnull (NOG) mice are humanized with CD34+ hematopoietic cells (huNOG mice) and are commonly utilized for biological or medical research on human therapeutics. In the present study, nine 26-week-old, female huNOG mice were utilized for testing proprietary immune-modulating drugs over a 3-week period at the University of Washington. Two of the 9 mice developed unilateral swelling of a tibiotarsal joint with associated paresis of the affected limb.

A small molecule mitigates hearing loss in a mouse model of Usher syndrome III.

Usher syndrome type III (USH3), characterized by progressive deafness, variable balance disorder and blindness, is caused by destabilizing mutations in the gene encoding the clarin-1 (CLRN1) protein. Here we report a new strategy to mitigate hearing loss associated with a common USH3 mutation CLRN1(N48K) that involves cell-based high-throughput screening of small molecules capable of stabilizing CLRN1(N48K), followed by a secondary screening to eliminate general proteasome inhibitors, and finally an iterative process to optimize structure-activity relationships. This resulted in the identification of BioFocus 844 (BF844).

Identification of a series of compounds with potent antiviral activity for the treatment of enterovirus infections.

Rhinovirus (genus enterovirus) infections are responsible for many of the severe exacerbations of asthma and chronic obstructive pulmonary disease. Other members of the genus can cause life-threatening acute neurological infections. There is currently no antiviral drug approved for the treatment of such infections.

Evaluation of an advanced-practice physical therapist in a specialty shoulder clinic: diagnostic agreement and effect on wait times.

Purpose: To examine the role of an advanced-practice physiotherapist (APP) with respect to (1) agreement with an orthopaedic surgeon on diagnosis and management of patients with shoulder problems; (2) wait times; and (3) satisfaction with care.

Methods: This prospective study involved patients with shoulder complaints who were referred to a shoulder specialist in a tertiary care centre. Agreement was examined on seven major diagnostic categories, need for further examination and surgery, and type of surgical procedure.

A novel, broad-spectrum inhibitor of enterovirus replication that targets host cell factor phosphatidylinositol 4-kinase IIIβ.

Despite their high clinical and socioeconomic impacts, there is currently no approved antiviral therapy for the prophylaxis or treatment of enterovirus infections. Here we report on a novel inhibitor of enterovirus replication, compound 1, 2-fluoro-4-(2-methyl-8-(3-(methylsulfonyl)benzylamino)imidazo[1,2-a]pyrazin-3-yl)phenol. This compound exhibited a broad spectrum of antiviral activity, as it inhibited all tested species of enteroviruses and rhinoviruses, with 50% effective concentrations ranging between 4 and 71 nM.

Global differences in dialysis modality mix: the role of patient characteristics, macroeconomics and renal service indicators.

Background: An increase in the dialysis programme expenditure is expected in most countries given the continued rise in the number of people with end-stage renal disease (ESRD) globally. Since chronic peritoneal dialysis (PD) therapy is relatively less expensive compared with haemodialysis (HD) and because there is no survival difference between PD and HD, identifying factors associated with PD use is important.

Methods: Incidence counts for the years 2003-05 were available from 36 countries worldwide.

Exploring the association between macroeconomic indicators and dialysis mortality.

Background And Objectives: Mortality on dialysis varies greatly worldwide, with patient-level factors explaining only a small part of this variation. The aim of this study was to examine the association of national-level macroeconomic indicators with the mortality of incident dialysis populations and explore potential explanations through renal service indicators, incidence of dialysis, and characteristics of the dialysis population.

Design, Setting, Participants, & Measurements: Aggregated unadjusted survival probabilities were obtained from 22 renal registries worldwide for patients starting dialysis in 2003-2005.

Translating chronic kidney disease epidemiology into patient care--the individual/public health risk paradox.

Background: Applying the Kidney Disease Outcomes Quality Initiative definitions of chronic kidney disease (CKD), it appears that CKD is common. The increased recognition of CKD has brought with it the clinical challenge of translating into practice the implications for the patient and for service planning. To understand the clinical relevance and translate that into information to support individual patient care and service planning, we explored clinical outcomes in a large British CKD cohort, identified through routine opportunistic testing, with a 6-year follow-up (≈ 13,000 patient-years).

Global variation in renal replacement therapy for end-stage renal disease.

Background: Incidence rates of renal replacement therapy (RRT) for end-stage renal disease vary considerably worldwide. This study examines the independent association between the general population, health care system and renal service characteristics and RRT incidence rates.

Methods: RRT incidence data (2003-2005) were obtained from renal registries; general population age and health and macroeconomic indices were collected from secondary sources.

Identification of an Orally Bioavailable, Potent, and Selective Inhibitor of GlyT1.

Amalgamation of the structure-activity relationship of two series of GlyT1 inhibitors developed at Merck led to the discovery of a clinical candidate, compound 16 (DCCCyB), which demonstrated excellent in vivo occupancy of GlyT1 transporters in rhesus monkey as determined by displacement of a PET tracer ligand.

Non-basic ligands for aminergic GPCRs: the discovery and development diaryl sulfones as selective, orally bioavailable 5-HT2A receptor antagonists for the treatment of sleep disorders.

Scaffold hopping from a non-basic series of 5-HT(2A) receptor antagonists developed in-house that possessed reduced activity in vivo enabled the discovery of a novel series of diaryl sulfones that gave excellent occupancy on oral dosing. Not only does this work further demonstrate that oral bioavailability of a given series can be enhanced by improving physicochemical parameters such as log P, but it corroborates the growing evidence that a protonated amine is not essential for affinity at aminergic GPCRs.

The EVEREST study: an international collaboration.

Rates of initiation of renal replacement therapy (RRT), use of home modalities of treatment and patient outcomes vary considerably between countries. This paper reports the methods and baseline characteristics of countries participating in the EVEREST study (n = 46), a global collaboration examining the association between medical and non-medical factors and RRT incidence, modality mix and survival. Numbers of incident and prevalent patients were collected for current (2003-05) and historic (1983-85, 1988-90, 1993-95 and 1998-2000) periods stratified, where available, by age, gender, treatment modality and cause of end stage renal disease (diabetic versus non-diabetic).

In vitro and in vivo properties of 3-tert-butyl-7-(5-methylisoxazol-3-yl)-2-(1-methyl-1H-1,2,4-triazol-5-ylmethoxy)-pyrazolo[1,5-d]-[1,2,4]triazine (MRK-016), a GABAA receptor alpha5 subtype-selective inverse agonist.

3-tert-Butyl-7-(5-methylisoxazol-3-yl)-2-(1-methyl-1H-1,2,4-triazol-5-ylmethoxy)-pyrazolo[1,5-d][1,2,4]triazine (MRK-016) is a pyrazolotriazine with an affinity of between 0.8 and 1.5 nM for the benzodiazepine binding site of native rat brain and recombinant human alpha1-, alpha2-, alpha3-, and alpha5-containing GABA(A) receptors.

Systematic review of antimicrobials for the prevention of haemodialysis catheter-related infections.

Background: Almost 30% of chronic haemodialysis (HD) patients are dependent on central venous catheters (CVCs) for their vascular access, and catheter-related bacteraemia (CRB) is the major reason for catheter loss and has been associated with substantial morbidity, including meta-static infections. This systematic review evaluates the benefits and harms of antimicrobial interventions for the prevention of catheter-related infections (CRIs).

Methods: MEDLINE (1950-May 2009), EMBASE (1980-May 2009) CENTRAL (up to May 2009) and bibliographies of retrieved articles were searched for relevant RCTs.

A framework for the development and implementation of an advanced practice role for physiotherapists that improves access and quality of care for patients.

A new model of care has been implemented at the Sunnybrook Holland Orthopaedic and Arthritic Centre that expands the role of physiotherapists to improve access and quality of care for patients requiring hip and knee replacement surgery. An advanced practice physiotherapist (APP) role was created to support both referral management and post-operative care to reduce surgeon workload and better streamline services. This article describes our nine-step framework for implementing an APP role and can be used as a template for other organizations evolving similar roles.

Toward a joint health and disease management program. Toronto hospitals partner to provide system leadership.

The Joint Health and Disease Management Program in the Toronto Central Local Health Integration Network (TC LHIN) is envisioned as a comprehensive model of care for patients with hip and knee arthritis. It includes access to assessment services, education, self-management programs and other treatment programs, including specialist care as needed. As the first phase of this program, the hospitals in TC LHIN implemented a Hip and Knee Replacement Program to focus on improving access and quality of care, coordinating services and measuring wait times for patients waiting for hip or knee replacement surgery.

Mid-infrared (2.75-6.0-microm) second-harmonic generation in LiInS(2).

Phase-matched second-harmonic generation is obtained in various LiInS(2) crystals by use of the tunable picosecond output of the free-electron laser for infrared experiments (FELIX) as the pump source in the mid-IR range from 2.75 to 6.0 microm.

Benchmarking of electro-optic monitors for femtosecond electron bunches.

The longitudinal profiles of ultrashort relativistic electron bunches at the soft x-ray free-electron laser FLASH have been investigated using two single-shot detection schemes: an electro-optic (EO) detector measuring the Coulomb field of the bunch and a radio-frequency structure transforming the charge distribution into a transverse streak. A comparison permits an absolute calibration of the EO technique. EO signals as short as 60 fs (rms) have been observed, which is a new record in the EO detection of single electron bunches and close to the limit given by the EO material properties.

Automated vs continuous ambulatory peritoneal dialysis: a systematic review of randomized controlled trials.

Background: A systematic review of randomized controlled trials (RCTs) comparing continuous ambulatory peritoneal dialysis (CAPD) with all forms of automated peritoneal dialysis (APD) was performed to assess their comparative clinical effectiveness.

Methods: The Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE, EMBASE and CINAHL, were searched for relevant RCTs. Analysis was by a random effects model and results expressed as relative risk (RR) and weighted mean difference (WMD) with 95% confidence intervals (CI).