To send content items to your account,
please confirm that you agree to abide by our usage policies.
If this is the first time you use this feature, you will be asked to authorise Cambridge Core to connect with your account.
Find out more about sending content to .
To send content items to your Kindle, first ensure firstname.lastname@example.org
is added to your Approved Personal Document E-mail List under your Personal Document Settings
on the Manage Your Content and Devices page of your Amazon account. Then enter the ‘name’ part
of your Kindle email address below.
Find out more about sending to your Kindle.
Note you can select to send to either the @free.kindle.com or @kindle.com variations.
‘@free.kindle.com’ emails are free but can only be sent to your device when it is connected to wi-fi.
‘@kindle.com’ emails can be delivered even when you are not connected to wi-fi, but note that service fees apply.
Background: SMA is characterized by reduced levels of survival of motor neuron (SMN) protein from deletions and/or mutations of the SMN1 gene. While SMN1 produces full-length SMN protein, a second gene, SMN2, produces low levels of functional SMN protein. Risdiplam (RG7916/RO7034067) is an investigational, orally administered, centrally and peripherally distributed small molecule that modulates pre-mRNA splicing of SMN2 to increase SMN protein levels. Methods: SUNFISH (NCT02908685) is an ongoing multicenter, double-blind, placebo-controlled, operationally seamless study (randomized 2:1, risdiplam:placebo) in patients aged 2–25 years, with Type 2/3 SMA. Part 1 (n=51) assesses safety, tolerability, pharmacokinetics and pharmacodynamics of different risdiplam dose levels. Pivotal Part 2 (n=180) assesses safety and efficacy of the risdiplam dose level selected based on Part 1 results. Results: Part 1 results showed a sustained, >2-fold increase in median SMN protein versus baseline following 1 year of treatment. Adverse events were mostly mild, resolved despite ongoing treatment and reflected underlying disease. No drug-related safety findings have led to withdrawal (data-cut 06/17/18). SUNFISH Part 1 exploratory endpoint results and Part 2 study design will also be presented. Conclusions: To date, no drug-related safety findings have led to withdrawal. Risdiplam led to sustained increases in SMN protein levels.
Infants with prenatally diagnosed CHD are at high risk for adverse outcomes owing to multiple physiologic and psychosocial factors. Lack of immediate physical postnatal contact because of rapid initiation of medical therapy impairs maternal–infant bonding. On the basis of expected physiology, maternal–infant bonding may be safe for select cardiac diagnoses.
This is a single-centre study to assess safety of maternal–infant bonding in prenatal CHD.
In total, 157 fetuses with prenatally diagnosed CHD were reviewed. On the basis of cardiac diagnosis, 91 fetuses (58%) were prenatally approved for bonding and successfully bonded, 38 fetuses (24%) were prenatally approved but deemed not suitable for bonding at delivery, and 28 (18%) were not prenatally approved to bond. There were no complications attributable to bonding. Those who successfully bonded were larger in weight (3.26 versus 2.6 kg, p<0.001) and at later gestation (39 versus 38 weeks, p<0.001). Those unsuccessful at bonding were more likely to have been delivered via Caesarean section (74 versus 49%, p=0.011) and have additional non-cardiac diagnoses (53 versus 29%, p=0.014). There was no significant difference regarding the need for cardiac intervention before hospital discharge. Infants who bonded had shorter hospital (7 versus 26 days, p=0.02) and ICU lengths of stay (5 versus 23 days, p=0.002) and higher survival (98 versus 76%, p<0.001).
Fetal echocardiography combined with a structured bonding programme can permit mothers and infants with select types of CHD to successfully bond before ICU admission and intervention.
Nighttime eating is often associated with a negative impact on weight management and cardiometabolic health. However, data from recent acute metabolic studies have implicated a benefit of ingesting a bedtime snack for weight management. The present study compared the impact of ingesting a milk snack containing either 10 (BS10) or 30 g (BS30) protein with a non-energetic placebo (BS0) 30 min before bedtime on next morning metabolism, appetite and energy intake in mildly overweight males (age: 24·3 (sem 0·8) years; BMI: 27·4 (sem 1·1) kg/m2). Next morning measurements of RMR, appetite and energy intake were measured using indirect calorimetry, visual analogue scales and an ad libitum breakfast, respectively. Bedtime milk ingestion did not alter next morning RMR (BS0: 7822 (sem 276) kJ/d, BS10: 7482 (sem 262) kJ/d, BS30: 7851 (sem 261) kJ/d, P=0·19) or substrate utilisation as measured by RER (P=0·64). Bedtime milk ingestion reduced hunger (P=0·01) and increased fullness (P=0·04) during the evening immediately after snack ingestion, but elicited no effect the next morning. Next morning breakfast (BS0: 2187 (sem 365) kJ, BS10: 2070 (sem 336) kJ, BS30: 2582 (sem 384) kJ, P=0·21) and 24 h post-trial (P=0·95) energy intake was similar between conditions. To conclude, in mildly overweight adults, compared with a non-energetic placebo, a bedtime milk snack containing 10 or 30 g of protein does not confer changes in next morning whole-body metabolism and appetite that may favour weight management.
The effect of transportation and lairage on the faecal shedding and post-slaughter contamination of carcasses with Escherichia coli O157 and O26 in young calves (4–7-day-old) was assessed in a cohort study at a regional calf-processing plant in the North Island of New Zealand, following 60 calves as cohorts from six dairy farms to slaughter. Multiple samples from each animal at pre-slaughter (recto-anal mucosal swab) and carcass at post-slaughter (sponge swab) were collected and screened using real-time PCR and culture isolation methods for the presence of E. coli O157 and O26 (Shiga toxin-producing E. coli (STEC) and non-STEC). Genotype analysis of E. coli O157 and O26 isolates provided little evidence of faecal–oral transmission of infection between calves during transportation and lairage. Increased cross-contamination of hides and carcasses with E. coli O157 and O26 between co-transported calves was confirmed at pre-hide removal and post-evisceration stages but not at pre-boning (at the end of dressing prior to chilling), indicating that good hygiene practices and application of an approved intervention effectively controlled carcass contamination. This study was the first of its kind to assess the impact of transportation and lairage on the faecal carriage and post-harvest contamination of carcasses with E. coli O157 and O26 in very young calves.
By imposing absorption lines of HF in stellar spectra we can measure changes in r.v. with a precision of ~10m/s from a single spectrum, provided stellar line profiles are not distorted by atmospheric motions. The precision of absolute radial velocities is currently limited to ~100m/s by knowledge of rest wavelengths. Representative results are presented from our three, active PRV programs: velocity variations of δ Scuti stars; a search for unseen companions to late-type stars; and routine observations of certain IAU velocity ‘standards’.
The first high accuracy VLBI measurements with the Hartebeesthoek Radio Astronomy Observatory (HartRAO) at the southern end of the African tectonic plate were made possible at the beginning of 1986 through the loan of a MARK III DAT to HartRAO by the US National Geodetic Survey. Six twenty-four hour experiments spread over thirty-three days were used to precisely determine the HartRAO station position and to measure baseline lengths to Europe and North America. Interleaved between these multi-station experiments, a single baseline from Wettzell to HartRAO was used for two hours on a daily basis in order to measure pole positions. The formal errors of the x and y pole component determinations for each day are about ±2 mas and ±1 mas respectively, but an offset of about 6 mas from the IRIS values remains to be investigated.
We developed a structure algorithm for the computation of phase- and group delay corrections to geodetic VLBI observations. For some of the sources, i.e. 3C454.3, 3C273B and 3C345 the corrections are in the range of several hundred picosecs of group delay.
Pertussis is a vaccine-preventable respiratory infection caused by Bordetella pertussis which can be fatal in infants. Although high vaccine coverage led to prolonged disease control in England, a national outbreak of pertussis in 2011 led to the largest increase in over two decades, including a marked increase in cases aged ⩾15 years. A case-control study in four regions of England was undertaken to investigate risk factors for pertussis in adolescents and adults, specifically employment type and professional and household contact with children. Pertussis cases were laboratory-confirmed and aged ⩾15 years. Controls were recruited through general practitioner nomination. Demographic and risk factor information were collected using an online survey. Multivariable logistic regression was used to estimate independent associations with outcome. Two hundred and thirty-one cases and 190 controls were recruited. None of the four employment variables (social care, education, health sector, patient contact) were significantly associated with pertussis. Professional contact with children aged < 1 year was associated with a significantly reduced odds of pertussis [odds ratio (OR) 0·25, 95% confidence interval (CI) 0·08–0·78, P = 0·017]. Household contact with ⩾1 child aged 10–14 years was associated with significantly increased odds of pertussis (OR 2·61, 95% CI 1·47–4·64, P = 0·001). Occupational contact with very young children was associated with reduced odds of pertussis, probably due to immune boosting by low-level exposures to B. pertussis. Sharing a household with a young adolescent was a significant risk factor for pertussis in adults and older teenagers. The primary focus of the childhood pertussis vaccination programmes is to prevent infant disease. Although evidence is emerging that adolescent vaccination does not provide indirect protection to infants, our results highlight the importance of children aged 10–14 years in pertussis transmission to older adolescents and adults.
The Southern Hemisphere VLBI Experiment (SHEVE) program is aimed at producing high-resolution images of southern radio sources. The radio telescopes of the present SHEVE array are described below and some recent results presented.
Background: Ataluren is the first drug to treat the underlying cause of nmDMD. Methods: ACT DMD is a Phase 3, randomized, double-blind study. Males 7-16 years with nmDMD and a screening six-minute walk distance (6MWD) ≥150 m and <80%-predicted were randomized to ataluren 40 mg/kg/day or placebo for 48 weeks. A pre-specified subgroup included patients with baseline 6MWD 300-400 m. A meta-analysis of the overall ACT DMD population and the ‘ambulatory decline phase’ subgroup of the Phase 2b study (those patients meeting ACT DMD entry criteria) was pre-specified in the statistical plan. Results: In the overall ACT DMD population (N=228), changes in TFTs favored ataluren over placebo: 10-meter walk/run, -1.2s (p=0.117); 4-stair climb, -1.8s (p=0.058); 4-stair descend, -1.8s (p=0.012). In the pre-specified subgroup (n=99), these differences increased to -2.1s, -3.6s, and -4.3s, respectively, and were statistically significant (p<0.01) for 4-stair climb and descend. Results are supported by the meta-analysis (N=291), which demonstrated significant differences (p<0.05) in 10-meter walk/run, 4-stair climb, 4-stair descend. Conclusions: TFT results showed a benefit for ataluren in ACT DMD, and a larger treatment effect in the pre-specified baseline 6MWD 300-400 m subgroup as well as the pre-specified meta-analysis of ACT DMD and the Phase 2b study decline subgroup.
Introduction: Acute upper gastrointestinal (UGI) bleeding is a relatively common emergency resulting in death in 6 to 8% of cases. UGI endoscopy is the intervention of choice which requires procedural sedation and analgesia (PSA). The Halifax Infirmary emergency department (ED) performs 1000 PSAs annually, performed by advanced care paramedics (ACPs). This has been shown safe for other indications for PSA, such as orthopedic procedures. Considering that UGI endoscopy involves upper airway manipulation, and patients are at an increased risk of massive bleeding, this procedure would be expected to be more complex and have an increased risk of adverse events (AEs). This study aims to compare PSA for UGI endoscopy performed by ACPs to that for orthopedic procedures for AEs, airway intervention and medication use. Methods: This study is a retrospective review of an ACP-performed ED PSA quality control database. A dataset was built matching 64 UGI endoscopy PSAs to 192 orthopedic PSAs by propensity scores calculated using age, gender and ASA classification. Outcomes assessed were hypotension (SBP < 100, or 15% decrease from baseline), hypoxia (SaO2 < 90), apnea (> 30sec), vomiting, arrhythmias and death in the ED. The need for airway intervention and medication use was assessed. Results: The UGI endoscopy group was 4.60 times more likely to suffer hypotension than the orthopedic group (OR=4.6, CI:2.2-9.6), and a fifth as likely to require airway repositioning (OR=0.2, CI:0.1-0.5). One endoscopy patient required endotracheal intubation. No patient died in either group. Compared to the orthopedic group, the UGI endoscopy group was one-third as likely to receive fentanyl (OR=0.3, CI:0.2-0.6). When fentanyl was administered, endoscopy patients received an average 26.7 mcg less than orthopedic patients. The endoscopy group was 15.4 times more likely to receive ketamine (OR=15.4, CI:4.7-66.5), and received 34.4 mg less on average. Four endoscopy patients received phenylephrine compared to none in the orthopedic group. There were no other differences. Conclusion: ED PSA for UGI endoscopy appears to differ significantly from that performed for orthopedic procedures. It was associated with more frequent hypotension and increased use of ketamine as a sedative. Patients undergoing UGI endoscopy were less likely to receive fentanyl and require airway repositioning. Only patients in the endoscopy group required intubation or a vasopressor agent.
PKS 1934–638 is an archetypal GPS source, peaking at 1.4 GHz and exhibits almost no flux density variability. VLBI images at frequencies of .843, 2.3, 4.8, & 8.4 were made with the southern hemisphere VLBI array and they reveal that the source is a 42 mas compact double. There is no detectable change in separation over the last 20 years, yielding an upper limit of ~ 0.03c ± 0.2c on any expansion velocity. The spectral shapes of the two components are remarkably similar, despite indications of finer structure on longer baselines. Magnetic field calculations indicate fields of a few mGauss and the results are consistent with equipartition.
While the summit of the Antarctic Plateau has long been expected to harbor the best ground-based sites for terahertz (THz) frequency astronomical investigations, it is only recently that direct observations of exceptional THz atmospheric transmission and stability have been obtained. These observations, in combination with recent technological advancements in astronomical instrumentation and autonomous field platforms, make the recognition and realization of terahertz observatories on the high plateau feasible and timely. Here, we will explore the context of terahertz astronomy in the era of Herschel, and the crucial role that observatories on the Antarctic Plateau can play. We explore the important scientific questions to which observations from this unique environment may be most productively applied. We examine the importance and complementarity of Antarctic THz astronomy in the light of contemporary facilities such as ALMA, CCAT, SOFIA and (U)LDB ballooning. Finally, building from the roots of THz facilities in Antarctica to present efforts, we broadly highlight future facilities that will exploit the unique advantages of the Polar Plateau and provide a meaningful, lasting astrophysical legacy.