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Background: We describe an infant with a diagnosis of GM3 synthase deficiency, presenting with severe neuroirritability from birth. He required multiple admissions due to extreme agitation and caregiver burnout. Multiple pharmacological agents were tried, and the effect of each medication was modest and short-lasting at best. The literature on the management of neuroirritability in children with progressive genetic and metabolic conditions is sparse, and a neuroirritability management protocol has yet to be developed at our institution. Methods: We searched for relevant primary research and articles on PubMed. We reviewed the evidence of each pharmacological agent and added non-pharmacological strategies. We developed management guidelines for neuroirritability at our hospital. This protocol was reviewed by several pediatric neurologists and pediatric palliative care specialists at the Stollery and SickKids Hospitals. Results: We present the Pediatric Neuroirritability Management Protocol for the Stollery Children’s Hospital. Conclusions: Further study is required to assess whether this protocol can be adapted to treat irritability in the context of other neurological conditions such as hypoxic-ischemic encephalopathy and non-accidental injury. In addition, we will expand our guidelines to include other symptoms such as spasticity, dystonia, and autonomic dysfunction.
Introduction: Prehospital field trauma triage (FTT) standards were reviewed and revised in 2014 based on the recommendations of the Centers for Disease Control and Prevention. The FTT standard allows a hospital bypass and direct transport, within 30 min, to a lead trauma hospital (LTH). Our objectives were to assess the impact of the newly introduced prehospital FTT standard and to describe the emergency department (ED) management and outcomes of patients that had bypassed closer hospitals. Methods: We conducted a 12-month multi-centred health record review of paramedic and ED records following the implementation of the 4 step FTT standard (step 1: vital signs and level of consciousness (physiologic), step 2: anatomical injury, step 3: mechanism and step 4: special considerations) in nine paramedic services across Eastern Ontario. We included adult trauma patients transported as urgent that met FTT standard, regardless of transport time. We developed and piloted a data collection tool and obtained consensus on all definitions. The primary outcome was the rate of appropriate triage to a LTH which was defined as: ISS ≥12, admitted to intensive care unit (ICU), non-orthopedic surgery, or death. We have reported descriptive statistics. Results: 570 patients were included: mean age 48.8, male 68.9%, falls 29.6%, motor vehicle collisions 20.2%, stab wounds 10.5%, transported to a LTH 76.5% (n = 436). 72.2% (n = 315) of patients transported to a LTH had bypassed a closer hospital and 126/306 (41.2%) of those were determined to be an appropriate triage to LTH (9 patients had missing outcomes). ED management included: CT head/cervical spine 69.9%, ultrasound 53.6%, xray 51.6%, intubation 15.0%, sedation 11.1%, tranexamic acid 9.8%, blood transfusion 8.2%, fracture reduction 6.9%, tube thoracostomy 5.9%. Outcomes included: ISS ≥ 12 32.7%, admitted to ICU 15.0%, non-orthopedic surgery 11.1%, death 8.8%. Others included: admission to hospital 57.5%, mean LOS 12.8 days, orthopedic surgery 16.3% and discharged from ED 37.3%. Conclusion: Despite a high number of admissions, the majority of trauma patients bypassed to a LTH were considered over-triaged, with a low number of ED procedures and non-orthopedic surgeries. Continued work is needed to appropriately identify patients requiring transport to a LTH.
Background: Electroconvulsive therapy (ECT) involves the induction of a generalized seizure with an electrical current and has been used worldwide when treating medically refractory psychiatric illness. Here we describe a patient with no prior history or risk factors for epilepsy who developed temporal lobe epilepsy after chronic treatment of ECT. Methods: A 16-year-old right-handed boy with severe refractory depression received ECT treatment every 10 days for 8 months. Six months into his ECT treatment, the patient developed seizures and was admitted to a pediatric epilepsy monitoring unit. Results: Initial clinical events included lightheadedness, diaphoresis, and nausea with associated kaleidoscopic vision changes. Seizures progressed to confusion, fear and paranoia by the time the patient was admitted for monitoring. Long-term video EEG captured many focal seizures with impaired awareness, all originating from both temporal lobes. MRI was normal. ECT was terminated and the patient started on carbamazepine. He has been seizure free for the past 2 years on medication Conclusions: While rare, we present a case of a patient with no prior risk factors for epilepsy who developed temporal lobe epilepsy after chronic ECT treatment. Although ECT is an indispensable treatment for many medically refractory psychiatric illnesses, we suggest caution in young patient undergoing ECT.
Introduction: Trauma and injury play a significant role in the population's burden of disease. Limited research exists evaluating the role of trauma bypass protocols. The objective of this study was to assess the impact and effectiveness of a newly introduced prehospital field trauma triage (FTT) standard, allowing paramedics to bypass a closer hospital and directly transport to a trauma centre (TC) provided transport times were within 30 minutes. Methods: We conducted a 12-month multi-centred health record review of paramedic call reports and emergency department health records following the implementation of the 4 step FTT standard (step 1: vital signs and level of consciousness, step 2: anatomical injury, step 3: mechanism and step 4: special considerations) in nine paramedic services across Eastern Ontario. We included adult trauma patients transported as an urgent transport to hospital, that met one of the 4 steps of the FTT standard and would allow for a bypass consideration. We developed and piloted a standardized data collection tool and obtained consensus on all data definitions. The primary outcome was the rate of appropriate triage to a TC, defined as any of the following: injury severity score ≥12, admitted to an intensive care unit, underwent non-orthopedic operation, or death. We report descriptive and univariate analysis where appropriate. Results: 570 adult patients were included with the following characteristics: mean age 48.8, male 68.9%, attended by Advanced Care Paramedic 71.8%, mechanisms of injury: MVC 20.2%, falls 29.6%, stab wounds 10.5%, median initial GCS 14, mean initial BP 132, prehospital fluid administered 26.8%, prehospital intubation 3.5%, transported to a TC 74.6%. Of those transported to a TC, 308 (72.5%) had bypassed a closer hospital prior to TC arrival. Of those that bypassed a closer hospital, 136 (44.2%) were determined to be “appropriate triage to TC”. Bypassed patients more often met the step 1 or step 2 of the standard (186, 66.9%) compared to the step 3 or step 4 (122, 39.6%). An appropriate triage to TC occurred in 104 (55.9%) patients who had met step 1 or 2 and 32 (26.2%) patients meeting step 3 or 4 of the FTT standard. Conclusion: The FTT standard can identify patients who should be bypassed and transported to a TC. However, this is at a cost of potentially burdening the system with poor sensitivity. More work is needed to develop a FTT standard that will assist paramedics in appropriately identifying patients who require a trauma centre.
The particle size of the forage has been proposed as a key factor to ensure a healthy rumen function and maintain dairy cow performance, but little work has been conducted on ryegrass silage (GS). To determine the effect of chop length of GS and GS:maize silage (MS) ratio on the performance, reticular pH, metabolism and eating behaviour of dairy cows, 16 multiparous Holstein-Friesian cows were used in a 4×4 Latin square design with four periods each of 28-days duration. Ryegrass was harvested and ensiled at two mean chop lengths (short and long) and included at two ratios of GS:MS (100:0 or 40:60 dry matter (DM) basis). The forages were fed in mixed rations to produce four isonitrogenous and isoenergetic diets: long chop GS, short chop GS, long chop GS and MS and short chop GS and MS. The DM intake (DMI) was 3.2 kg/day higher (P<0.001) when cows were fed the MS than the GS-based diets. The short chop length GS also resulted in a 0.9 kg/day DM higher (P<0.05) DMI compared with the long chop length. When fed the GS:MS-based diets, cows produced 2.4 kg/day more (P<0.001) milk than when fed diets containing GS only. There was an interaction (P<0.05) between chop length and forage ratio for milk yield, with a short chop length GS increasing yield in cows fed GS but not MS-based diets. An interaction for DM and organic matter digestibility was also observed (P<0.05), where a short chop length GS increased digestibility in cows when fed the GS-based diets but had little effect when fed the MS-based diet. When fed the MS-based diets, cows spent longer at reticular pH levels below pH 6.2 and pH 6.5 (P<0.01), but chop length had little effect. Cows when fed the MS-based diets had a higher (P<0.05) milk fat concentration of C18 : 2n-6 and total polyunsaturated fatty acids compared with when fed the GS only diets. In conclusion, GS chop length had little effect on reticular pH, but a longer chop length reduced DMI and milk yield but had little effect on milk fat yield. Including MS reduced reticular pH, but increased DMI and milk performance irrespective of the GS chop length.
Improving access to tuberculosis (TB) care and ensuring early diagnosis are two major aims of the WHO End TB strategy and the Collaborative TB Strategy for England. This study describes risk factors associated with diagnostic delay among TB cases in England. We conducted a retrospective cohort study of TB cases notified to the Enhanced TB Surveillance System in England between 2012 and 2015. Diagnostic delay was defined as more than 4 months between symptom onset and treatment start date. Multivariable logistic regression was used to identify demographic and clinical factors associated with diagnostic delay. Between 2012 and 2015, 22 422 TB cases were notified in England and included in the study. A third (7612) of TB cases had a diagnostic delay of more than 4 months. Being female, aged 45 years and older, residing outside of London and having extra-pulmonary TB disease were significantly associated with a diagnostic delay in the multivariable model (aOR = 1.2, 1.2, 1.2, 1.3, 1.8, respectively). This study identifies demographic and clinical factors associated with diagnostic delay, which will inform targeted interventions to improve access to care and early diagnosis among these groups, with the ultimate aim of helping reduce transmission and improve treatment outcomes for TB cases in England.
Established methods of recruiting population controls for case–control studies to investigate gastrointestinal disease outbreaks can be time consuming, resulting in delays in identifying the source or vehicle of infection. After an initial evaluation of using online market research panel members as controls in a case–control study to investigate a Salmonella outbreak in 2013, this method was applied in four further studies in the UK between 2014 and 2016. We used data from all five studies and interviews with members of each outbreak control team and market research panel provider to review operational issues, evaluate risk of bias in this approach and consider methods to reduce confounding and bias. The investigators of each outbreak reported likely time and cost savings from using market research controls. There were systematic differences between case and control groups in some studies but no evidence that conclusions on the likely source or vehicle of infection were incorrect. Potential selection biases introduced by using this sampling frame and the low response rate are unclear. Methods that might reduce confounding and some bias should be balanced with concerns for overmatching. Further evaluation of this approach using comparisons with traditional methods and population-based exposure survey data is recommended.
Background: Cerebral palsy (CP) is a debilitating disorder (1). Based on neuromotor impairments it is divided to spastic, dyskinetic and ataxic types (2). Inborn Errors of Metabolism (IEMs), monogenic and chromosomal disorders mimic CP (3). We aimed to identify causal genetic variants in patients with atypical dyskinetic CP in whom known IEMs were ruled out. Timely diagnosis is essential for proper management, especially in conditions that mimic CP and are treatable. Methods: We enrolled 23 patients with unexplained atypical dyskinetic CP, for whole exome sequencing. Variants were filtered against public and in-house databases to identify variants predicted as damaging (in silico tools and ACMG criteria). We applied a virtual gene panel of known and suspected CP and movement disorder genes and investigated each sample. Results: The participants presented with symptoms including: spasticity, dystonia, choera-athetosis, ataxia and cognitive delays. We identified 23 diagnoses: 13 dominant,6 recessive and 4 X-linked. 12 patients had movement disorders. In 4, the diagnoses enabled targeted treatment (neurotransmitter supplements in Unverricht Lundborg diseases (CSTB) and PAK3 deficiency, deep brain stimulation in GNAO1 deficiency, medical diet in Glutaric Aciduria (GCDH). Conclusions: Whole Exome Sequencing contributes to establishing diagnosis in patients with atypical dyskinetic CP resulting in precision medicine and improved health outcomes.
Introduction: In Ottawa, STEMI patients are transported directly to percutaneous coronary intervention (PCI) by advanced care paramedics (ACPs), primary care paramedics (PCPs), or transferred from PCP to ACP crew (ACP-intercept). PCPs have a limited skill set to address complications during transport.The objective of this study was to determine what clinically important events (CIEs) occurred in STEMI patients transported for primary PCI via a PCP crew, and what proportion of such events could only be treated by ACP protocols. Methods: We conducted a health record review of STEMI patients transported for primary PCI from Jan 1, 2011-Dec 21, 2015. Ottawa has a single PCI center and its EMS system employs both PCP and ACP paramedics. We identified consecutive STEMI bypass patients transported by PCP-only and ACP-intercept using the dispatch database. A data extraction form was piloted and used to extract patient demographics, transport times, and primary outcomes: CIEs and interventions performed during transport, and secondary outcomes: hospital diagnosis, and mortality. CIEs were reviewed by two investigators to determine if they would be treated differently by ACP protocols. We present descriptive statistics. Results: We identified 967 STEMI bypass cases among which 214 (118 PCP-only and 96 ACP-intercept) met all inclusion criteria. Characteristics were: mean age 61.4 years, 78% male, 31.8% anterior and 44.4% inferior infarcts, mean response time 6 min, total paramedic contact time 29 min, and in cases of ACP-intercept 7 min of PCP-only contact time.A CIE occurred in 127 (59%) of cases: SBP<90 mmHg 26.2%, HR<60 30.4%, HR>100 20.6%, malignant arrhythmias 7.5%, altered mental status 6.5%, airway intervention 2.3%, 2 patients (0.9%) arrested, both survived. Of the CIE identified, 54 (42.5%) could be addressed differently by ACP vs PCP protocols (25.2% of total cases). The majority related to fluid boluses for hypotension (44 cases; 35% of CIE). ACP intervention for CIEs within the ACP intercept group was 51.6%. There were 6 in-hospital deaths (2.8%) with no difference in transport crew type. Conclusion: CIEs are common in STEMI bypass patients however a smaller proportion of such CIE would be addressed differently by ACP protocols compared to PCP protocols. The vast majority of CIE appeared to be transient and of limited clinical significance.
Introduction: The Canadian C-Spine Rule (CCR) was validated by emergency physicians and triage nurses to determine the need for radiography in alert and stable Emergency Department trauma patients. It was modified and validated for use by paramedics in 1,949 patients. The prehospital CCR calls for evaluation of active neck rotation if patients have none of 3 high-risk criteria and at least 1 of 4 low-risk criteria. This study evaluated the impact and safety of the implementation of the CCR by paramedics. Methods: This single-centre prospective cohort implementation study took place in Ottawa, Canada. Advanced and primary care paramedics received on-line and in-person training on the CCR, allowing them to use the CCR to evaluate eligible patients and selectively transport them without immobilization. We evaluated all consecutive eligible adult patients (GCS 15, stable vital signs) at risk for neck injury. Paramedics were required to complete a standardized study data form for each eligible patient evaluated. Study staff reviewed paramedic documentation and corresponding hospital records and diagnostic imaging reports. We followed all patients without initial radiologic evaluation for 30 days for referral to our spine service, or subsequent visit with radiologic evaluation. Analyses included sensitivity, specificity, kappa coefficient, t-test, and descriptive statistics with 95% CIs. Results: The 4,034 patients enrolled between Jan. 2011 and Aug. 2015 were: mean age 43 (range 16-99), female 53.3%, motor vehicle collision 51.9%, fall 23.8%, admitted to hospital 7.0%, acute c-spine injury 0.8%, and clinically important c-spine injury (0.3%). The CCR classified patients for 11 important injuries with sensitivity 91% (95% CI 58-100%), and specificity 67% (95% CI 65-68%). Kappa agreement for interpretation of the CCR between paramedics and study investigators was 0.94 (95% CI 0.92-0.95). Paramedics were comfortable or very comfortable using the CCR in 89.8% of cases. Mean scene time was 3 min (15.6%) shorter for those not immobilized (17 min vs. 20 min; p=0.0001). A total of 2,569 (63.7%) immobilizations were safely avoided using the CCR. Conclusion: Paramedics could safely and accurately apply the CCR to low-risk trauma patients. This had a significant impact on scene times and the number of prehospital immobilizations.
Considered as a less hazardous piezoelectric material, potassium sodium niobate (KNN) has been in the fore of the search for replacement of lead (Pb) zirconate titanate for piezoelectrics applications. Here, we challenge the environmental credentials of KNN due to the presence of ~60 wt% Nb2O5, a substance much less toxic to humans than Pb oxide, but whose mining and extraction cause significant environmental damage.
In October 2014, Public Health England (PHE) identified cases of Shiga toxin-producing Escherichia coli (STEC) serogroup O157 sharing a multiple locus variable-number tandem repeat analysis (MLVA) profile. We conducted a case-control study using multivariable logistic regression to calculate adjusted odds ratios (aOR) and 95% confidence intervals (CI) testing a range of exposures. Cases were defined as laboratory-confirmed STEC O157 with the implicated MLVA profile, were UK residents aged ⩾18 years with symptom onset between 25 September and 30 October 2014, and had no history of travel abroad within 5 days of symptom onset. One hundred and two cases were identified. Cases were mostly female (65%; median age 49, range 2–92 years). It was the second largest outbreak seen in England, to date, and a case-control study was conducted using market research panel controls and online survey methods. These methods were instrumental in the rapid data collection and analysis necessary to allow traceback investigations for short shelf-life products. This is a new method of control recruitment and this is the first in which it was a standalone recruitment method. The case-control study suggested a strong association between consumption of a ready-to-eat food and disease (aOR 28, 95% CI 5·0–157) from one retailer. No reactive microbiological testing of food items during the outbreak was possible due to the short shelf-life of the product. Collaboration with industrial bodies is needed to ensure timely traceback exercises to identify contamination events and initiate appropriate and focused microbiological testing and implement control measures.
The galactopoietic effect of growth hormone (GH) in lactating ruminants is well established; however the mechanisms that mediate these effects are not well understood. The first objective of this study was to determine the effect of GH on the synthesis of the major casein and whey proteins. The second objective was to identify the genes and pathways that may be involved in mediating the effect of GH on milk synthesis. A single subcutaneous injection of a commercially available slow release formulation of GH (Lactatropin®), or physiological saline solution (control) was administered to non-pregnant dairy cows (n=4/group) in mid-late lactation. Milk samples were collected for composition analysis and mammary lobulo-alveolar tissue was collected postmortem 6 days post injection. Gene expression profiles were evaluated using either a 22 000 bovine complementary DNA microarray or quantitative PCR (qPCR), and microarrays were validated by qPCR. The yield of all the major casein and whey proteins was increased 32% to 41% in GH-treated cows, with the exception of α-lactalbumin yield which was elevated by 70% relative to controls. Treatment with GH treatment tended to increase the concentration of α-lactalbumin but had no effect on the concentration of any of the major milk proteins. Messenger RNA (mRNA) abundance of the major whey and casein genes, with the exception of α-s2-casein, was increased in response to GH compared with controls, which is consistent with the positive effect of GH on milk production. Treatment with GH treatment influenced the mRNA abundance of genes involved in cell growth and proliferation, transcriptional and translational regulation, actin cytoskeleton signalling, lipid metabolism and cell death. This study has provided new insights into the cell signalling that may be involved in mediating the effect of GH on milk production in the mammary gland of lactating dairy cows.
Although only three antennas of the Australia Telescope Compact Array are currently operational, we have made use of the technique of bandwidth synthesis to make an image of the radio galaxy 2152 – 69. The three baselines were used to observe the source at three different frequencies, effectively resulting in nine baselines, which have been used to produce an image with a surprisingly high dynamic range, and with a slightly higher resolution than any existing image.
The production of such a worthwhile result, despite being made with a small subset of the capabilities of the Australia Telescope, bodes well for the future operation of the instrument.
Several extragalactic HI surveys using a λ21 cm 13-beam focal plane array will begin in early 1997 using the Parkes 64 m telescope. These surveys are designed to detect efficiently nearby galaxies that have failed to be identified optically because of low optical surface brightness or high optical extinction. We discuss scientific and technical aspects of the multibeam receiver, including astronomical objectives, feed, receiver and correlator design and data acquisition. A comparison with other telescopes shows that the Parkes multibeam receiver has significant speed advantages for any large-area λ21 cm galaxy survey in the velocity range range 0–14000 km s−1.
To determine the functional integrity of the neural systems involved in emotional responding/regulation and response control/inhibition in youth (age 10–18 years) with disruptive behavioral disorders (DBDs: conduct disorder and/or oppositional defiant disorder) as a function of callous-unemotional (CU) traits.
Twenty-eight healthy youths and 35 youths with DBD [high CU (HCU), n = 18; low CU (LCU), n = 17] performed the fMRI Affective Stroop task. Participants viewed positive, neutral, and negative images under varying levels of cognitive load. A 3-way ANOVA (group×emotion by task) was conducted on the BOLD response data.
Youth with DBD-HCU showed significantly less activation of ventromedial prefrontal cortex (vmPFC) and amygdala in response to negative stimuli, compared to healthy youth and youth with DBD-LCU. vmPFC responsiveness was inversely related to CU symptoms in DBD. Youth with DBD-LCU showed decreased functional connectivity between amygdala and regions including inferior frontal gyrus in response to emotional stimuli. Youth with DBD (LCU and HCU) additionally showed decreased insula responsiveness to high load (incongruent trials) compared to healthy youth. Insula responsiveness was inversely related to ADHD symptoms in DBD.
These data reveal two forms of pathophysiology in DBD. One associated with reduced amygdala and vmPFC responses to negative stimuli and related to increased CU traits. Another associated with reduced insula responses during high load task trials and related to ADHD symptoms. Appropriate treatment will need to be individualized according to the patient's specific pathophysiology.
It is well-established that altering the proportion of starch and fibre in ruminant diets can alter ruminal and post-ruminal digestion, although quantitative evidence that this reduces enteric methane (CH4) production in dairy cattle is lacking. The objective of this study was to examine the effect of varying grass-to-maize silage ratio (70 : 30 and 30 : 70 DM basis), offered ad libitum, with either a concentrate that was high in starch or fibre, on CH4 production, intake, performance and milk composition of dairy cows. A total of 20 cows were allocated to one of the four experimental diets in a two-by-two factorial design run as a Latin square with each period lasting 28 days. Measurements were conducted during the final 7 days of each period. Cows offered the high maize silage ration had a higher dry matter intake (DMI), milk yield, milk energy output and lower CH4 emissions when expressed per kg DMI and per unit of ingested gross energy, but there was no difference in total CH4 production. Several of the milk long-chain fatty acids (FA) were affected by forage treatment with the most notable being an increase in 18:0, 18:1 c9, 18:2 c9 c12 and total mono unsaturated FA, observed in cows offered the higher inclusion of maize silage, and an increase in 18:3 c9 c12 c15 when offered the higher grass silage ration. Varying the composition of the concentrate had no effect on DMI or milk production; however, when the high-starch concentrate was fed, milk protein concentration and milk FAs, 10:0, 14:1, 15:0, 16:1, increased and 18:0 decreased. Interactions were observed for milk fat concentration, being lower in cows offered high-grass silage and high-fibre concentrates compared with the high-starch concentrate, and FA 17:0, which was the highest in milk from cows fed the high-grass silage diet supplemented with the high-starch concentrate. In conclusion, increasing the proportion of maize silage in the diets of dairy cows increased intake and performance, and reduced CH4 production, but only when expressed on a DM or energy intake basis, whereas starch-to-fibre ratio in the concentrate had little effect on performance or CH4 production.