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Hereditary transthyretin-mediated (hATTR) amyloidosis is a progressive disease caused by mutations in the TTR gene leading to multisystem organ dysfunction. Pathogenic TTR aggregation, misfolding, and fibrillization lead to deposition of amyloid in multiple body organs and frequently involve the peripheral nerve system and the heart. Common neurologic manifestations include: sensorimotor polyneuropathy (PN), autonomic neuropathy, small-fiber PN, and carpal tunnel syndrome. Many patients have significant progression due to diagnostic delays as hATTR PN is not considered within the differential diagnosis. Recently, two effective novel disease-modifying therapies, inotersen and patisiran, were approved by Health Canada for the treatment of hATTR PN. Early diagnosis is crucial for the timely introduction of these disease-modifying treatments that reduce impairments, improve quality of life, and extend survival. In this guideline, we aim to improve awareness and outcomes of hATTR PN by making recommendations directed to the diagnosis, monitoring, and treatment in Canada.
We present a sediment-mixing process model of till genesis based on data from surface tills of the Saginaw lobe terrain in lower Michigan. Our research uses a spatial approach to understanding glacial landsystems and till genesis. We sampled calcareous till at 336 upland sites and at 17 sites in lacustrine sediment of the Saginaw Lake plain. The loamy tills have bimodal grain-size curves, with a fine-texture mode near the silt–clay boundary and a sand mode. Spatial grouping analysis suggests that tills can be divided into six groups, each with different textures and clay mineral compositions that vary systematically down-ice. The similarity among groups with respect to the silt–clay mode and clay mineralogy argues for a common origin for the fines—illite-rich lacustrine sediment of the Saginaw Lake plain. Fine-textured sediments were probably entrained, transported, and deposited down-ice as till, which also becomes sandier and enriched in kaolinite, reflecting increasing mixing with shallow sandstone bedrock with distance from the lacustrine clay source. Clayey tills on the flanks of the Saginaw terrain may reflect proglacial ponding against nearby uplands. A process model of progressive down-ice mixing of preexisting fine lake sediments with crushed/abraded sandstone bedrock helps to better explain till textures compared with a purely crushing/abrasion process model.
Duchenne muscular dystrophy is associated with progressive cardiorespiratory failure, including left ventricular dysfunction.
Methods and Results:
Males with probable or definite diagnosis of Duchenne muscular dystrophy, diagnosed between 1 January, 1982 and 31 December, 2011, were identified from the Muscular Dystrophy Surveillance Tracking and Research Network database. Two non-mutually exclusive groups were created: patients with ≥2 echocardiograms and non-invasive positive pressure ventilation-compliant patients with ≥1 recorded ejection fraction. Quantitative left ventricular dysfunction was defined as an ejection fraction <55%. Qualitative dysfunction was defined as mild, moderate, or severe. Progression of quantitative left ventricular dysfunction was modelled as a continuous time-varying outcome. Change in qualitative left ventricle function was assessed by the percentage of patients within each category at each age. Forty-one percent (n = 403) had ≥2 ejection fractions containing 998 qualitative assessments with a mean age at first echo of 10.8 ± 4.6 years, with an average first ejection fraction of 63.1 ± 12.6%. Mean age at first echo with an ejection fraction <55 was 15.2 ± 3.9 years. Thirty-five percent (140/403) were non-invasive positive pressure ventilation-compliant and had ejection fraction information. The estimated rate of decline in ejection fraction from first ejection fraction was 1.6% per year and initiation of non-invasive positive pressure ventilation did not change this rate.
In our cohort, we observed that left ventricle function in patients with Duchenne muscular dystrophy declined over time, independent of non-invasive positive pressure ventilation use. Future studies are needed to examine the impact of respiratory support on cardiac function.
Neurodegenerative disorders, including Alzheimer's (AD) and Parkinson's diseases (PD), are characterised by the formation of aberrant assemblies of misfolded proteins. The discovery of disease-modifying drugs for these disorders is challenging, in part because we still have a limited understanding of their molecular origins. In this review, we discuss how biophysical approaches can help explain the formation of the aberrant conformational states of proteins whose neurotoxic effects underlie these diseases. We discuss in particular models based on the transgenic expression of amyloid-β (Aβ) and tau in AD, and α-synuclein in PD. Because biophysical methods have enabled an accurate quantification and a detailed understanding of the molecular mechanisms underlying protein misfolding and aggregation in vitro, we expect that the further development of these methods to probe directly the corresponding mechanisms in vivo will open effective routes for diagnostic and therapeutic interventions.
Pelagic seabirds often nest on islands that are far from productive foraging areas. The Procellariiformes (petrels, shearwaters and albatrosses) are among the longest-ranging seabirds; they have several adaptations that permit them to efficiently utilize distant foraging areas and fast for long periods during incubation (Phillips & Hamer 1999). Giant petrels (Macronectes spp.) are large surface-nesting procellariiforms. They feed both by direct predation and by scavenging carrion, and they are the largest avian predator-scavengers in the Southern Ocean. Among procellariiform seabirds, one partner forages while their mate remains on the nest to incubate their single egg (Warham 1990). Northern giant petrels (Macronectes halli) have incubation shifts lasting up to 17 days (Cooper et al. 2001). In general, incubating procellariiform seabirds do not feed during their shift (Warham 1990). We report the first case to our knowledge of a procellariiform seabird, a northern giant petrel, actively feeding at its nest whilst incubating.
While echocardiographic parameters are used to quantify ventricular function in infants with single ventricle physiology, there are few data comparing these to invasive measurements. This study correlates echocardiographic measures of diastolic function with ventricular end-diastolic pressure in infants with single ventricle physiology prior to superior cavopulmonary anastomosis.
Data from 173 patients enrolled in the Pediatric Heart Network Infant Single Ventricle enalapril trial were analysed. Those with mixed ventricular types (n = 17) and one outlier (end-diastolic pressure = 32 mmHg) were excluded from the analysis, leaving a total sample size of 155 patients. Echocardiographic measurements were correlated to end-diastolic pressure using Spearman’s test.
Median age at echocardiogram was 4.6 (range 2.5–7.4) months. Median ventricular end-diastolic pressure was 7 (range 3–19) mmHg. Median time difference between the echocardiogram and catheterisation was 0 days (range −35 to 59 days). Examining the entire cohort of 155 patients, no echocardiographic diastolic function variable correlated with ventricular end-diastolic pressure. When the analysis was limited to the 86 patients who had similar sedation for both studies, the systolic:diastolic duration ratio had a significant but weak negative correlation with end-diastolic pressure (r = −0.3, p = 0.004). The remaining echocardiographic variables did not correlate with ventricular end-diastolic pressure.
In this cohort of infants with single ventricle physiology prior to superior cavopulmonary anastomosis, most conventional echocardiographic measures of diastolic function did not correlate with ventricular end-diastolic pressure at cardiac catheterisation. These limitations should be factored into the interpretation of quantitative echo data in this patient population.
This study investigated the role of sequential processing in spoken language outcomes for children who are deaf or hard of hearing (DHH), ages 5;3–11;4, by comparing them to children with typical hearing (TH), ages 6;3–9;7, on sequential learning and memory tasks involving easily nameable and difficult-to-name visual stimuli. Children who are DHH performed more poorly on easily nameable sequencing tasks, which positively predicted receptive vocabulary scores. Results suggest sequential learning and memory may underlie delayed language skills of many children who are DHH. Implications for language development in children who are DHH are discussed.
Recent evidence suggests that exercise plays a role in cognition and that the posterior cingulate cortex (PCC) can be divided into dorsal and ventral subregions based on distinct connectivity patterns.
To examine the effect of physical activity and division of the PCC on brain functional connectivity measures in subjective memory complainers (SMC) carrying the epsilon 4 allele of apolipoprotein E (APOE 4) allele.
Participants were 22 SMC carrying the APOE ɛ4 allele (ɛ4+; mean age 72.18 years) and 58 SMC non-carriers (ɛ4–; mean age 72.79 years). Connectivity of four dorsal and ventral seeds was examined. Relationships between PCC connectivity and physical activity measures were explored.
ɛ4+ individuals showed increased connectivity between the dorsal PCC and dorsolateral prefrontal cortex, and the ventral PCC and supplementary motor area (SMA). Greater levels of physical activity correlated with the magnitude of ventral PCC–SMA connectivity.
The results provide the first evidence that ɛ4+ individuals at increased risk of cognitive decline show distinct alterations in dorsal and ventral PCC functional connectivity.
We extend the behavioral ethics literature to examining emotional labor as an antecedent to unethical behavior. We hypothesize that surface acting is positively associated with unethical behavior. In contrast, we produce competing hypotheses for the relationship between deep acting and unethical behavior. In Study 1, with a field sample of 123 full-time employees, surface acting was positively associated with unethical behavior, and emotional inauthenticity explained some of this relationship. In contrast, deep acting was not associated with unethical behavior. In Study 2, with a field sample of 117 full-time employees, we replicated the effect of surface acting in Study 1 and found a positive relationship between deep acting and unethical behavior via emotional inauthenticity. In Study 3, using a two-wave design, we replicated the results in Study 2 and found perceived fairness strengthens the relationship between surface acting and unethical behavior through emotional inauthenticity.
In northern Turkey, the Intra-Pontide suture zone represents one of the first-order tectonic structures located between the Istanbul–Zonguldak and the Sakarya continental terranes. It consists of an E–W-trending assemblage of deformed and variably metamorphosed tectonic units, including sedimentary rocks and ophiolites derived from a Neo-Tethyan oceanic basin, known as the Intra-Pontide oceanic basin. One of these units is represented by the Daday Unit that consists of a block-in-matrix assemblage derived from supra-subduction oceanic crust and related deep-sea sedimentary cover of Middle Jurassic age. This setting was acquired during Late Jurassic time by tectonic underplating at a depth of 35–42 km associated with blueschist-facies metamorphism (D1 phase). The following D2, D3 and D4 phases produced the exhumation of the Daday Unit up to shallower structural levels in a time span running from the Albian to late Paleocene. The high geothermal gradient detected during the D2 phase indicates that the Daday Unit was exhumed during a continent–arc collisional setting. The tectonic structures of the Intra-Pontide suture zone, resulting from the previously described tectonic history, are unconformably sealed by the upper Paleocene – Eocene deposits. This tectonic setting was intensely reworked by the activity of the North Anatolian Fault Zone, producing the present-day geometrical relationships of the Intra-Pontide suture zone of the Central Pontides.
During mass-casualty incidents (MCIs), patient volume often overwhelms available Emergency Medical Services (EMS) personnel. First responders are expected to triage, treat, and transport patients in a timely fashion. If other responders could triage accurately, prehospital EMS resources could be focused more directly on patients that require immediate medical attention and transport.
Triage accuracy, error patterns, and time to triage completion are similar between second-year primary care paramedic (PCP) and fire science (FS) students participating in a simulated MCI using the Sort, Assess, Life-saving interventions, Treatment/Transport (SALT) triage algorithm.
All students in the second-year PCP program and FS program at two separate community colleges were invited to participate in this study. Immediately following a 30-minute didactic session on SALT, participants were given a standardized briefing and asked to triage an eight-victim, mock MCI using SALT. The scenario consisted of a four-car motor vehicle collision with each victim portrayed by volunteer actors given appropriate moulage and symptom coaching for their pattern of injury. The total number and acuity of victims were unknown to participants prior to arrival to the mock scenario.
Thirty-eight PCP and 29 FS students completed the simulation. Overall triage accuracy was 79.9% for PCP and 72.0% for FS (∆ 7.9%; 95% CI, 1.2-14.7) students. No significant difference was found between the groups regarding types of triage errors. Over-triage, under-triage, and critical errors occurred in 10.2%, 7.6%, and 2.3% of PCP triage assignments, respectively. Fire science students had a similar pattern with 15.2% over-triaged, 8.7% under-triaged, and 4.3% critical errors. The median [IQR] time to triage completion for PCPs and FSs were 142.1 [52.6] seconds and 159.0 [40.5] seconds, respectively (P=.19; Mann-Whitney Test).
Primary care paramedics performed MCI triage more accurately than FS students after brief SALT training, but no difference was found regarding types of error or time to triage completion. The clinical importance of this difference in triage accuracy likely is minimal, suggesting that fire services personnel could be considered for MCI triage depending on the availability of prehospital medical resources and appropriate training.
LeeCWC, McLeodSL, Van AarsenK, KlingelM, FrancJM, PeddleMB. First Responder Accuracy Using SALT during Mass-casualty Incident Simulation. Prehosp Disaster Med. 2016;31(2):150–154.
Influenza A (H1N1) pdm09 became the predominant circulating strain in the United States during the 2013–2014 influenza season. Little is known about the epidemiology of severe influenza during this season.
A retrospective cohort study of severely ill patients with influenza infection in intensive care units in 33 US hospitals from September 1, 2013, through April 1, 2014, was conducted to determine risk factors for mortality present on intensive care unit admission and to describe patient characteristics, spectrum of disease, management, and outcomes.
A total of 444 adults and 63 children were admitted to an intensive care unit in a study hospital; 93 adults (20.9%) and 4 children (6.3%) died. By logistic regression analysis, the following factors were significantly associated with mortality among adult patients: older age (>65 years, odds ratio, 3.1 [95% CI, 1.4–6.9], P=.006 and 50–64 years, 2.5 [1.3–4.9], P=.007; reference age 18–49 years), male sex (1.9 [1.1–3.3], P=.031), history of malignant tumor with chemotherapy administered within the prior 6 months (12.1 [3.9–37.0], P<.001), and a higher Sequential Organ Failure Assessment score (for each increase by 1 in score, 1.3 [1.2–1.4], P<.001).
Risk factors for death among US patients with severe influenza during the 2013–2014 season, when influenza A (H1N1) pdm09 was the predominant circulating strain type, shifted in the first postpandemic season in which it predominated toward those of a more typical epidemic influenza season.
Infect. Control Hosp. Epidemiol. 2015;36(11):1251–1260
Behavioural studies investigating word processing in bilinguals generally report faster response times (RTs) for first (L1) than for second (L2) language words. To examine the locus of this language effect, this study used behavioural data and event-related potentials (ERPs) collected from bilinguals while performing a semantic categorisation task on visual word pairs. RTs revealed both language and semantic relatedness effects. Spatio-temporal analysis of ERP map series showed that the semantic effect was explained by a condition-specific map segment occurring during the N400 component. The language effect was primarily explained by a map segment that started at ~170 ms and covered the period of the P2 component, that was longer in L2 than in L1 and whose duration correlated with RTs. Source localisation showed that this early segment involved the bilateral occipito-temporal regions including the fusiform area. These findings indicate that ERPs differentiated L1 and L2 during early word recognition steps.