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An improved understanding of diagnostic and treatment practices for patients with rare primary mitochondrial disorders can support benchmarking against guidelines and establish priorities for evaluative research. We aimed to describe physician care for patients with mitochondrial diseases in Canada, including variation in care.
We conducted a cross-sectional survey of Canadian physicians involved in the diagnosis and/or ongoing care of patients with mitochondrial diseases. We used snowball sampling to identify potentially eligible participants, who were contacted by mail up to five times and invited to complete a questionnaire by mail or internet. The questionnaire addressed: personal experience in providing care for mitochondrial disorders; diagnostic and treatment practices; challenges in accessing tests or treatments; and views regarding research priorities.
We received 58 survey responses (52% response rate). Most respondents (83%) reported spending 20% or less of their clinical practice time caring for patients with mitochondrial disorders. We identified important variation in diagnostic care, although assessments frequently reported as diagnostically helpful (e.g., brain magnetic resonance imaging, MRI/MR spectroscopy) were also recommended in published guidelines. Approximately half (49%) of participants would recommend “mitochondrial cocktails” for all or most patients, but we identified variation in responses regarding specific vitamins and cofactors. A majority of physicians recommended studies on the development of effective therapies as the top research priority.
While Canadian physicians’ views about diagnostic care and disease management are aligned with published recommendations, important variations in care reflect persistent areas of uncertainty and a need for empirical evidence to support and update standard protocols.
The difference in the defect structures produced by different ion masses in a tungsten lattice is investigated using 80 MeV Au7+ ions and 10 MeV B3+ ions. The details of the defects produced by ions in recrystallized tungsten foil samples are studied using transmission electron microscopy. Dislocations of type b = 1/2 and  were observed in the analysis. While highly energetic gold ion produced small clusters of defects with very few dislocation lines, boron has produced large and sparse clusters with numerous dislocation lines. The difference in the defect structures could be due to the difference in separation between primary knock-on atoms produced by gold and boron ions.
United Arab Emirates is an important range country for the ‘Vulnerable’ Socotra Cormorant Phalacrocorax nigrogularis and Abu Dhabi Emirate holds most of the remaining breeding colonies. Emirate-wide monitoring of all breeding colonies was undertaken annually for 11 breeding seasons from 2006–2007 to 2016–2017 to monitor the status of breeding colonies and estimate the nesting population. Breeding was recorded in 10 colonies that were used intermittently with an average of four (± 1.3 SD) colonies active each year. The highest number of eight active colonies was recorded in 2016–2017. Establishment of two new breeding colonies on Butinah and Digala in 2016–2017 and recolonisation of three previously inactive colonies during the monitoring period emphasised the ability of the species to relocate and colonise suitable sites. Continued threats at some breeding colonies caused abandonment and subsequent relocation, resulting in a gradual shift of breeding colonies to safer areas. Presently, most of the breeding sites (62%) with an increased number of breeding birds are found in colonies with restricted access. The Emirate-wide nesting population witnessed a 10-fold increase in the last decade; after an initial decline in 2006–2007 it increased from about 5,000 pairs in 2007–2008 to nearly 52,000 nesting pairs in 2016–2017. Combined with the nesting population from the Siniya colony, the overall UAE nesting population is estimated at 60,000 to 70,000 pairs, nearly half of the global breeding population. Further augmentation of the current breeding numbers is possible if breeding colonies remain safe from human disturbance and invasive predators. For long-term conservation of Socotra Cormorant, protection of all remaining colony sites, including inactive ones, is important in addition to minimising disturbance along with widespread public awareness to change the people’s perception of the species as a competitor to commercial fisheries.
The advancement of human retinal pigment epithelial cell (hRPE) replacement therapy is partly dependent on optimization of cell culture, cell preservation, and storage medium. This study was undertaken to search for a suitable storage temperature and storage medium for hRPE. hRPE monolayer sheets were cultured under standard conditions at 37°C and then randomized for storage at six temperatures (4, 16, 20, 24, 28, and 37°C) for 7 days. After revealing a suitable storage temperature, hRPE sheets were subsequently stored with and without the silk protein sericin added to the storage medium. Live/dead assay, light microscopy, pH, and phenotypic expression of various proteins were used to assess cell cultures stored at different temperatures. After 7 days of storage, hRPE morphology was best preserved at 4°C. Addition of sericin to the storage medium maintained the characteristic morphology of the preserved cells, and improved pigmentation and levels of pigmentation-related proteins in the cultured hRPE sheets following a 7-day storage period at 4°C.
The timing and origin of Zika virus (ZIKV) introduction in Brazil has been the subject of controversy. Initially, it was assumed that the virus was introduced during the FIFA World Cup in June–July 2014. Then, it was speculated that ZIKV may have been introduced by athletes from French Polynesia (FP) who competed in a canoe race in Rio de Janeiro in August 2014. We attempted to apply mathematical models to determine the most likely time window of ZIKV introduction in Brazil. Given that the timing and origin of ZIKV introduction in Brazil may be a politically sensitive issue, its determination (or the provision of a plausible hypothesis) may help to prevent undeserved blame. We used a simple mathematical model to estimate the force of infection and the corresponding individual probability of being infected with ZIKV in FP. Taking into account the air travel volume from FP to Brazil between October 2013 and March 2014, we estimated the expected number of infected travellers arriving at Brazilian airports during that period. During the period between December 2013 and February 2014, 51 individuals travelled from FP airports to 11 Brazilian cities. Basing on the calculated force of ZIKV infection (the per capita rate of new infections per time unit) and risk of infection (probability of at least one new infection), we estimated that 18 (95% CI 12–22) individuals who arrived in seven of the evaluated cities were infected. When basic ZIKV reproduction numbers greater than one were assumed in the seven evaluated cities, ZIKV could have been introduced in any one of the cities. Based on the force of infection in FP, basic reproduction ZIKV number in selected Brazilian cities, and estimated travel volume, we concluded that ZIKV was most likely introduced and established in Brazil by infected travellers arriving from FP in the period between October 2013 and March 2014, which was prior to the two aforementioned sporting events.
Background: Morphometry and connectivity studies targeting the thalamus have revealed specific patterns of atrophy and deafferentiation in patients with temporal lobe epilepsy (TLE). We used probabilistic tractography to investigate thalamic connectivity with respect to duration of epilepsy and surgical outcomes in TLE. Methods: Patients (N=20) with drug-resistant TLE (10 short duration (<15 years), 10 long duration (>15 years)) were scanned with multi-parametric 3T MRI and compared with 34 healthy controls. The Harvard-Oxford atlas was modified to create 14 target regions in the temporal lobes. Probabilistic tractography (FSL) was used to delineate thalamic sub-regions most connected to each target. The volume, mean T1, T2, FA and MD of each thalamic sub-region was quantified. Surgical success was quantified using Engel outcome scores. Results: Significant decreases in thalamic connected volumes to the hippocampus in patients with longer duration of TLE were revealed. Likewise, when stratified based on surgical success, significant differences in diffusion metrics to the hippocampus, parahippocampal gyrus, and temporal neocortex were found. Significant differences did not withstand false discovery rate (FDR) correction. Conclusions: These findings suggest ongoing connectivity changes dependent on epilepsy duration and promote further investigation into the use of thalamic connectivity data as biomarkers for predicting surgical outcomes in TLE patients.
Background: Childhood epilepsy has increased in global incidence. Children with epilepsy require immediate healthcare evaluation and monitoring. Waiting times between first seizure onset and pediatric neurology assessment may impact seizure outcome at follow-up. Quality of medical care for children with first seizure onset will be assessed and the impact of pediatric neurology clinic waiting times on seizure outcomes will be determined Methods: This retrospective study, based on chart review, includes patients with first seizure evaluation at the Royal University Hospital in Saskatoon between January 2012 and December 2015. The interim period before first assessment and other factors were studied in relation to seizure outcome on follow-up. Results: 1158 patients were assessed. 378 (32.6%) patients had first seizure clinic assessment. 197 (52%) had epileptic events. 181 (48%) had non-epileptic events. The mean age of patients was 8.8 years. The mean waiting time for assessment by a pediatric neurologist was 4.33 months. The mean duration of follow-up was 20.9 months. At the last seizure assessment, 132 patients were free of seizures and 65 patients had a recurrence of seizures. Conclusions: First seizure assessment is crucial for management of children with epilepsy. Waiting time and other factors may influence seizure outcome, representing opportunities to improve standard medical care.
The present study was conducted to appraise the ontogenic radio-sensitivity of a serious tropical pest, Spodoptera litura (Fabr.). The molecular responses pertaining to the phenoloxidase (PO) pathway and an anti-oxidant defense mechanism were evaluated in order to understand its implication in pest control at pre-harvest and post-harvest intervals. Irradiation exhibited an inverse relationship with age with respect to impact on developmental and transcriptional responses. Transcript abundance of PO cascade enzymes, prophenoloxidase (slppo-2), its activating enzyme (slppae-1) and free-radical scavenging enzymes, superoxide dismutase (slsod) and catalase (slcat) was evaluated upon gamma irradiation alone and the dual-stress of radiation plus microbial challenge. The slppo-2, slppae-1, slsod and slcat transcripts were significantly up-regulated in F1 L6 larvae (6th-instar) resulting from 100 Gy sub-sterilized male adults and unirradiated female moths. The extent of upregulation was relatively higher in comparison with L6 survivors (6th-instar larvae) developed from irradiated neonates (L1) treated with 100 Gy. Upon Photorhabdus challenge, the transcripts were down-regulated in irradiated L1 suggesting increased larval susceptibility to bacterial infections. Radioresistance increased with the age of the insect, and molecular responses (transcript abundance) of insect defense mechanism were less influenced when older age (F1 progeny) were irradiated. These findings will help to optimize the gamma dose to be employed in inherited sterility technique for (pre-harvest) pest suppression and (post-harvest) phytosanitation and quarantine, and suggest compatible integration of biorational tactics including nuclear technology.
Background: The clinical identification of hippocampal sclerosis (HS) is important in predicting surgical outcomes in patients with temporal lobe epilepsy (TLE). In cases where gross hippocampal sclerosis is not identifiable clinically, a more detailed analysis of hippocampal subfields using ultra-high-field magnetic resonance imaging (MRI) may reveal areas of abnormality, which was the focus of our study. Methods: Patients (N=13) with drug-resistant TLE (9 no-HS, 4 HS) and 20 age-matched healthy controls were scanned and compared using a 7T MRI protocol. Using a manual segmentation scheme to delineate hippocampal subfields, subfield-specific volume changes were studied between the two groups. In addition, radiological patient assessment at 7T was correlated with measured subfield changes. Results: Volumetry of the hippocampus at 7T in HS patients revealed significant ipsilateral subfield losses in CA1 and CA4DG. Volumetry also uncovered subfield volume losses in 33% of no-HS patients, which had not been detected conventionally. Furthermore, 89% of no-HS patients showed abnormality (internal architecture or size) at 7T, identified by radiologists blinded to the patient’s initial classification. Conclusions: These preliminary findings indicate that hippocampal subfield volumetry assessed at 7T may be superior to conventional visual inspection by a neuroradiologist in the identification of hippocampal pathologies in TLE.
Pompe disease is a lysosomal storage disorder caused by a deficiency of the enzyme acid alpha-glucosidase. Patients have skeletal muscle and respiratory weakness with or without cardiomyopathy. The objective of our review was to systematically evaluate the quality of evidence from the literature to formulate evidence-based guidelines for the diagnosis and management of patients with Pompe disease. The literature review was conducted using published literature, clinical trials, cohort studies and systematic reviews. Cardinal treatment decisions produced seven management guidelines and were assigned a GRADE classification based on the quality of evidence in the published literature. In addition, six recommendations were made based on best clinical practices but with insufficient data to form a guideline. Studying outcomes in rare diseases is challenging due to the small number of patients, but this is in particular the reason why we believe that informed treatment decisions need to consider the quality of the evidence.
The French economy has been criticized for a lack of integration of women in business and for the prevalence of inefficient family firms. A sample drawn from patent and exhibition records is used to examine the role of women in enterprise and invention in France. Middle-class women were extensively engaged in entrepreneurship and innovation, and the empirical analysis indicates that their commercial efforts were significantly enhanced by association with family firms. Such formerly invisible achievements suggest a more productive role for family-based enterprises, as a means of incorporating relatively disadvantaged groups into the market economy as managers and entrepreneurs.
“This business model … melds entrepreneurial passion with a long family tradition.”
Prizes for innovations are currently experiencing a renaissance, following their marked decline during the nineteenth century. Debates about such incentive mechanisms tend to employ canonical historical anecdotes to motivate and support the analysis and policy proposals. Daguerre's “patent buyout,” the Longitude Prize, inducement prizes for butter substitutes and billiard balls, the activities of the Royal Society of Arts and other “encouragement” institutions—all comprise potentially misleading case studies. The article surveys and summarizes extensive empirical research using samples drawn from Britain, France, and the United States, including “great inventors” and their ordinary counterparts, and prizes at industrial exhibitions. The results suggest that administered systems of rewards to innovators suffered from a number of disadvantages in design and practice, which might be inherent to their nonmarket orientation.
Harvesting solar energy, is only one of the incentives of incorporating photosynthetic proteins in electrochemical devices. Understanding the interface of photosynthetic protein complexes and organic\inorganic underlying electrodes can give rise to development of new generation of nano-bioelectronics for other applications such as sensing, as well. Previous approaches in fabricating photosynthetic bio-hybrid electrochemical solar cells were mainly based on metallic electrodes with protein complexes attached, either directly or through linker molecules. Due to the energy band structure in semiconductors, they potentially can be useful for selective charge transfer in an electrochemical device. In the current study, a two terminal sealed bio-hybrid solar cell device was fabricated comprising of hydrothermally grown ZnO nanowires on fluorine doped tin oxide (FTO) glass working electrode, a Pt counter electrode, and methyl viologen (MV) as a single diffusible redox mediator. The ZnO working electrode was initially characterized using scanning electron microscopy (XRD) and X-ray diffraction (XRD). A solution of dimeric Rhodobacter sphaeroides – light harvesting 1 (RC-LH1) core complexes and redox electrolyte was injected into the cavity between working and counter electrodes. Such structure resulted in ∼0.64 µA.cm-2 photocurrent density and ∼0.24 V open circuit potential difference in the dark and under illumination. Additionally, the device stability tests demonstrated that the current response of such devices remained unchanged after 33 hours storage in the dark.
Background: It has been hypothesized that [18F]-sodium fluoride (NaF) uptake imaged with positron emission tomography (PET) binds to hydroxyapatite molecules expressed in regions with active calcification. Therefore, we aimed to validate NaF as a marker of hydroxyapatite expression in high-risk carotid plaque. Methods: Eleven patients (69 ± 5 years, 3 female) scheduled for carotid endarterectomy were prospectively recruited for NaF PET/CT. One patient received a second contralateral endarterectomy; two patients were excluded (intolerance to contrast media and PET/CT misalignment). The bifurcation of the common carotid was used as the reference point; NaF uptake (tissue to blood ratio - TBR) was measured at every PET slice extending 2 cm above and below the bifurcation. Excised plaque was immunostained with Goldner’s Trichrome and whole-slide digitized images were used to quantify hydroxyapatite expression. Pathology was co-registered with PET. Results: NaF uptake was related to the extent of hydroxyapatite expression (r=0.45, p<0.001). Upon classifying bilateral plaque for symptomatology, symptomatic plaque was associated with cerebrovascular events (3.75±1.1 TBR, n=9) and had greater NaF uptake than clinically silent asymptomatic plaque (2.79±0.6 TBR, n=11) (p=0.04). Conclusion: NaF uptake is related to hydroxyapatite expression and is increased in plaque associated with cerebrovascular events. NaF may serve as a novel biomarker of active calcification and plaque vulnerability.
Central line–associated bloodstream infection (BSI) rates are a key quality metric for comparing hospital quality and safety. Traditional BSI surveillance may be limited by interrater variability. We assessed whether a computer-automated method of central line–associated BSI detection can improve the validity of surveillance.
Retrospective cohort study.
Eight medical and surgical intensive care units (ICUs) in 4 academic medical centers.
Traditional surveillance (by hospital staff) and computer algorithm surveillance were each compared against a retrospective audit review using a random sample of blood culture episodes during the period 2004–2007 from which an organism was recovered. Episode-level agreement with audit review was measured with κ statistics, and differences were assessed using the test of equal κ coefficients. Linear regression was used to assess the relationship between surveillance performance (κ) and surveillance-reported BSI rates (BSIs per 1,000 central line–days).
We evaluated 664 blood culture episodes. Agreement with audit review was significantly lower for traditional surveillance (κ [95% confidence interval (CI)] = 0.44 [0.37–0.51]) than computer algorithm surveillance (κ [95% CI] [0.52–0.64]; P = .001). Agreement between traditional surveillance and audit review was heterogeneous across ICUs (P = .001); furthermore, traditional surveillance performed worse among ICUs reporting lower (better) BSI rates (P = .001). In contrast, computer algorithm performance was consistent across ICUs and across the range of computer-reported central line–associated BSI rates.
Compared with traditional surveillance of bloodstream infections, computer automated surveillance improves accuracy and reliability, making interfacility performance comparisons more valid.
Infect Control Hosp Epidemiol 2014;35(12):1483–1490
The current gold-standard therapeutic strategies for bone grafts in the patient population are to use either allograft or autograft bone. Although these approaches have a long track record of utilization, neither is without risk to the patient, and there remains a desire in the field to improve treatment options. While there have been treatments approved by the FDA for full length growth factors and calcium salt-laden collagen sponges, these are not available for the entire population of potential bone graft patients. One viable strategy to focus on these concerns is to design an implantable bone graft substitute that can address all the negative drawbacks of autograft bone, allograft bone, and full length proteins. The work provides a preliminary investigation of synthetic, nanofiber-permeated, composite polymer/ceramic scaffold for bone repair using thermally induced phase separation, PLLA microspheres, and hydroxyapatite. The scaffolds as described have fiber diameters that mimic natural collagen ECM networks in bone as determined by scanning electron microscopy and will serve as the basis for future studies in substrate-guided bone tissue regeneration.