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 email@example.com
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.
Benzodiazepine (BZD) prescription rates have increased over the past decade in the United States. Available literature indicates that sociodemographic factors may influence diagnostic patterns and/or prescription behaviour. Herein, the aim of this study is to determine whether the gender of the prescriber and/or patient influences BZD prescription.
Cross-sectional study using data from the Florida Medicaid Managed Medical Assistance Program from January 1, 2018 to December 31, 2018. Eligible recipients ages 18 to 64, inclusive, enrolled in the Florida Medicaid plan for at least 1 day, and were dually eligible. Recipients either had a serious mental illness (SMI), or non-SMI and anxiety.
Total 125 463 cases were identified (i.e., received BZD or non-BZD prescription). Main effect of patient and prescriber gender was significant F(1, 125 459) = 0.105, P = 0 .745, partial η2 < 0.001. Relative risk (RR) of male prescribers prescribing a BZD compared to female prescribers was 1.540, 95% confidence intervals (CI) [1.513, 1.567], whereas the RR of male patients being prescribed a BZD compared to female patients was 1.16, 95% CI [1.14, 1.18]. Main effects of patient and prescriber gender were statistically significant F(1, 125 459) = 188.232, P < 0.001, partial η2 = 0.001 and F(1, 125 459) = 349.704, P < 0.001, partial η2 = 0.013, respectively.
Male prescribers are more likely to prescribe BZDs, and male patients are more likely to receive BZDs. Further studies are required to characterize factors that influence this gender-by-gender interaction.
Patients unsuccessfully treated by neurostimulation may represent a highly intractable subgroup of depression. While the efficacy of intravenous (IV) ketamine has been established in patients with treatment-resistant depression (TRD), there is an interest to evaluate its effectiveness in a subpopulation with a history of neurostimulation.
This retrospective, posthoc analysis compared the effects of four infusions of IV ketamine in 135 (x̄ = 44 ± 15.4 years of age) neurostimulation-naïve patients to 103 (x̄ = 47 ± 13.9 years of age) patients with a history of neurostimulation. The primary outcome evaluated changes in depression severity, measured by the Quick Inventory for Depression Symptomatology-Self Report 16-Item (QIDS-SR16). Secondary outcomes evaluated suicidal ideation (SI), anxiety severity, measured by the Generalized Anxiety Disorder 7-Item (GAD-7), and consummatory anhedonia, measured by the Snaith–Hamilton Pleasure Scale (SHAPS).
Following four infusions, both cohorts reported a significant reduction in QIDS-SR16 Total Score (F (4, 648) = 73.4, P < .001), SI (F (4, 642) = 28.6, P < .001), GAD-7 (F (2, 265) = 53.8, P < .001), and SHAPS (F (2, 302) = 45.9, P < .001). No between-group differences emerged. Overall, the neurostimulation-naïve group had a mean reduction in QIDS-SR16 Total Score of 6.4 (standard deviation [SD] = 5.3), whereas the history of neurostimulation patients reported a 4.3 (SD = 5.3) point reduction.
IV ketamine was effective in reducing symptoms of depression, SI, anxiety, and anhedonia in both cohorts in this large, well-characterized community-based sample of adults with TRD.
Higher body mass index (BMI) has been found to predict greater antidepressant response to intravenous (IV) ketamine treatment. We evaluated the association between BMI and response to repeat-dose IV ketamine in patients with treatment-resistant depression (TRD).
Adults (N = 230) with TRD received four infusions of IV ketamine at a community-based clinic. Changes in symptoms of depression (ie, Quick Inventory for Depressive Symptomatology-Self-Report 16; QIDS-SR16), suicidal ideation (SI; ie, QIDS-SR16 SI item), anxiety (ie, Generalized Anxiety Disorder-7 Scale), anhedonic severity (ie, Snaith–Hamilton Pleasure Scale), and functioning (ie, Sheehan Disability Scale) following infusions were evaluated. Participants were stratified by BMI as normal (18.0-24.9 kg/m2; n = 72), overweight (25-29.9 kg/m2; n = 76), obese I (30-34.9 kg/m2; n = 47), or obese II (≥35.0 kg/m2; n = 35).
Similar antidepressant effects with repeat-dose ketamine were reported between BMI groups (P = .261). In addition, categorical partial response (P = .149), response (P = .526), and remission (P = .232) rates were similar between the four BMI groups.
The findings are limited by the observational, open-label design of this retrospective analysis. Pretreatment BMI did not predict response to IV ketamine, which was effective regardless of BMI.
The shapes of two steadily rotating, equal circulation, two-dimensional hollow vortices are determined and their properties examined. By means of a numerical scheme that accounts for the doubly connected nature of the fluid domain, it is shown that a one-parameter family of solutions exists that is a continuation of a corotating point-vortex pair. With $b=2$ set as the distance between the vortex centroids, we find that each vortex reaches a maximum possible area of $0.796$ corresponding to $a/b=0.260$ where $a$ is a measure of the vortex core radius proposed by Meunier et al. (Phys. Fluids, vol. 14, 2002, pp. 2757–2766). Results are compared to those of a previous study by Saffman & Szeto (Phys. Fluids, vol. 23, 1980, pp. 2339–2342) in which two corotating patches of uniform vorticity are considered in place of the hollow vortices studied here. The general behaviour of the two systems is seen to be similar but some differences are highlighted, especially when the vortices become close to touching due to the accumulation of vorticity in thin extended fingers emanating from each of the vortices. The numerical scheme captures the family of equilibria very close to a critical configuration where these fingers tend to touch at the centre of rotation corresponding to $a/b \approx 0.283$. By a simple adaptation of the numerical scheme to compute $2$-fold rotationally symmetric equilibria for a single rotating hollow vortex we then show that its limiting configuration is one where a thin waist forms leading to two separate parts of its single boundary drawing close together. We give evidence that the limit of this single vortex configuration coincides with the limit of the two-vortex configuration. The limiting configuration itself turns out not to be physically admissible, leading to what we refer to as a topological singularity since no physical quantities blow up, indeed they appear to be continuous as the limiting state is approached from the two topologically distinct directions.
Two randomized, controlled trials of L-methylfolate augmentation of SSRIs for major depressive disorder (MDD) were conducted using a novel study design (sequential parallel comparison design- SPCD).
To evaluate the efficacy of L-methylfolate augmentation using the Hamilton Depression Rating Scale.
In study one (TRD-1), 148 outpatients with SSRI-resistant MDD were enrolled in a 60-day, SPCD study, divided into two 30-day periods (phases 1 and 2). Patients were randomized 2:3:3 to receive L-methylfolate (7.5mg/d in phase 1, 15mg/d in phase 2), placebo in phase 1 followed by L-methylfolate 7.5mg/d in phase 2, or placebo for both phases. Study two (TRD-2) involved 75 patients and was identical in design to TRD-1 except for the dose of L-methylfolate (15mg only).
In the TRD-1 Study, L-methylfolate 7.5 mg/d was not found to be more effective than placebo. In phase 1 of the TRD-2 Study, 37% of patients on L-methylfolate 15mg/d responded and 18% of placebo patients responded, while in phase 2 among placebo non-responders, the response rates were 28% on L-methylfolate 15mg/d and 9.5% on placebo. When phases 1 and 2 were pooled according to the SPCD model, the difference in response rates was statistically significant in favor of L-methylfolate (p = 0.0399). The rates of spontaneously reported AEs and rates of study discontinuation appear r comparable between L-methylfolate and placebo in both studies. Rates of study discontinuation were also comparable
These studies suggest that L-methylfolate 15 mg/d may be a safe and effective augmentation strategy for inadequate response to SSRIs.
Concurrent chemotherapy with radiotherapy is the standard treatment for locoregionally advanced nasopharyngeal cancer. Cetuximab can be used in the treatment of head and neck squamous cell carcinoma. However, the randomised studies that led to approval for its use in this setting excluded nasopharyngeal cancer. In the context of limited data for the use of cetuximab in nasopharyngeal cancer in the medical literature, this review aimed to summarise the current evidence for its use in both primary and recurrent or metastatic disease.
A literature search was performed using the keywords ‘nasopharyngeal neoplasm’, ‘cetuximab’ and ‘Erbitux’.
Twenty studies were included. There were no randomised phase III trials, but there were nine phase II trials. The use of cetuximab in the treatment of nasopharyngeal carcinoma has been tested in various settings, including in combination with induction chemotherapy and concurrent chemoradiotherapy, and in the palliative setting.
There is no evidence of benefit from the addition of cetuximab to standard management protocols, and there is some evidence of increased toxicity. There is more promise for its use in metastatic or locally recurrent settings. This review draws together the existing evidence and could provide a focus for future studies.
The COllaborative project of Development of Anthropometrical measures in Twins (CODATwins) project is a large international collaborative effort to analyze individual-level phenotype data from twins in multiple cohorts from different environments. The main objective is to study factors that modify genetic and environmental variation of height, body mass index (BMI, kg/m2) and size at birth, and additionally to address other research questions such as long-term consequences of birth size. The project started in 2013 and is open to all twin projects in the world having height and weight measures on twins with information on zygosity. Thus far, 54 twin projects from 24 countries have provided individual-level data. The CODATwins database includes 489,981 twin individuals (228,635 complete twin pairs). Since many twin cohorts have collected longitudinal data, there is a total of 1,049,785 height and weight observations. For many cohorts, we also have information on birth weight and length, own smoking behavior and own or parental education. We found that the heritability estimates of height and BMI systematically changed from infancy to old age. Remarkably, only minor differences in the heritability estimates were found across cultural–geographic regions, measurement time and birth cohort for height and BMI. In addition to genetic epidemiological studies, we looked at associations of height and BMI with education, birth weight and smoking status. Within-family analyses examined differences within same-sex and opposite-sex dizygotic twins in birth size and later development. The CODATwins project demonstrates the feasibility and value of international collaboration to address gene-by-exposure interactions that require large sample sizes and address the effects of different exposures across time, geographical regions and socioeconomic status.
We present the case of a 17-year-old boy with a cardiac venous malformation. This case highlights the diagnostic challenges of such tumours and demonstrates the potential efficacy of a watch-and-wait management approach.
Introduction: Frailty is a state of vulnerability affecting older adults, and has been associated with adverse events such as increased risk of institutionalization, falls, functional decline, and mortality. Previous research suggests that emergency department (ED) physicians are much less comfortable managing the complex care needs of frail, older adults. The objective of this study was to identify successful strategies and expert skills that ED physicians possess to optimally manage the frail, older patient. Methods: An interpretive descriptive qualitative study was conducted. One of the investigators contacted the site leads of 12 academic and community EDs across Canada to identify ED physicians who they perceived as being highly skilled in the care of frail, older patients. 22 individual physicians were identified and 13 physicians representing 10 EDs were invited to participate in a 30-minute semi-structured interview. Transcripts were coded by two members of the research team. Data collection is ongoing and analyses will occur until thematic saturation. Results: All participants indicated they were very comfortable managing the frail, older patient in the ED. Awareness of issues related to this patient population were triggered by both clinical and personal experiences, as well as institutional priorities. When asked how they developed their specific skills for this patient population, participants stated they received limited formal training during residency and early practise, but relied on situational learning, access to role models and engagement in self-directed learning. Participants identified three predominant management strategies for the care of the frail, older patient: thorough patient interaction at the start of the clinical encounter to maximize efficiency; engaging in teamwork to manage complex issues; and early involvement of the family/caregivers. Interestingly, not all participants used the term frailty, however most reflected principles of the concept in their discussion. Conclusion: Currently, principles of caring for frail, older adults are not widespread in emergency medicine residency training. These findings suggest that frailty care frequently requires an alternative clinical approach, which is often derived from personal experience, self-directed and experiential learning. Future educational initiatives should derive, implement and evaluate a wide-spread curriculum to teach the skills required to optimally care for these patients.
Introduction: Little is known about the variety of roles volunteers play in the emergency department (ED), and the potential impact they have on patient experience. The objective of this scoping review was to identify published and unpublished reports that described volunteer programs in EDs, and determine how these programs impacted patient experiences or outcomes. Methods: Electronic searches of Medline, EMBASE, Cochrane Central Register of Controlled Trials, Cochrane Database of Systematic Reviews and CINAHL were conducted and reference lists were hand-searched. A grey literature search was also conducted (Web of Science, ProQuest, Canadian Business and Current Affairs Database ProQuest Dissertations and Theses Global). Two reviewers independently screened titles and abstracts, reviewed full text articles, and extracted data. Results: The search strategy yielded 4,589 potentially relevant citations. After eliminating duplicate citations and articles that did not meet eligibility criteria, 87 reports were included in the review. Of the included reports, 18 were peer-reviewed articles, 6 were conference proceedings, 59 were magazine or newspaper articles, and 4 were graduate dissertations or theses. Volunteer activities were categorized as non-clinical tasks (e.g., provision of meals/snacks, comfort items and mobility assistance), navigation, emotional support/communication, and administrative duties. 52 (59.8%) programs had general volunteers in the ED and 35 (40.2%) had volunteers targeting a specific patient population, including pediatrics, geriatrics, patients with mental health and addiction issues and other vulnerable populations. 20 (23.0%) programs included an evaluative component describing how ED volunteers affected patient experiences and outcomes. Patient satisfaction, follow-up and referral rates, ED and hospital costs and length of stay, subsequent ED visits, medical complications, and malnutrition in the hospital were all reported to be positively affected by volunteers in the ED. Conclusion: This scoping review demonstrates the important role volunteers play in enhancing patient and caregiver experience in the ED. Future volunteer engagement programs implemented in the ED should be formally described and evaluated to share their success and experience with others interested in implementing similar programs in the ED.
The majority of paediatric Clostridioides difficile infections (CDI) are community-associated (CA), but few data exist regarding associated risk factors. We conducted a case–control study to evaluate CA-CDI risk factors in young children. Participants were enrolled from eight US sites during October 2014–February 2016. Case-patients were defined as children aged 1–5 years with a positive C. difficile specimen collected as an outpatient or ⩽3 days of hospital admission, who had no healthcare facility admission in the prior 12 weeks and no history of CDI. Each case-patient was matched to one control. Caregivers were interviewed regarding relevant exposures. Multivariable conditional logistic regression was performed. Of 68 pairs, 44.1% were female. More case-patients than controls had a comorbidity (33.3% vs. 12.1%; P = 0.01); recent higher-risk outpatient exposures (34.9% vs. 17.7%; P = 0.03); recent antibiotic use (54.4% vs. 19.4%; P < 0.0001); or recent exposure to a household member with diarrhoea (41.3% vs. 21.5%; P = 0.04). In multivariable analysis, antibiotic exposure in the preceding 12 weeks was significantly associated with CA-CDI (adjusted matched odds ratio, 6.25; 95% CI 2.18–17.96). Improved antibiotic prescribing might reduce CA-CDI in this population. Further evaluation of the potential role of outpatient healthcare and household exposures in C. difficile transmission is needed.
Laser-based compact MeV X-ray sources are useful for a variety of applications such as radiography and active interrogation of nuclear materials. MeV X rays are typically generated by impinging the intense laser onto ~mm-thick high-Z foil. Here, we have characterized such a MeV X-ray source from 120 TW (80 J, 650 fs) laser interaction with a 1 mm-thick tantalum foil. Our measurements show X-ray temperature of 2.5 MeV, flux of 3 × 1012 photons/sr/shot, beam divergence of ~0.1 sr, conversion efficiency of ~1%, that is, ~1 J of MeV X rays out of 80 J incident laser, and source size of 80 m. Our measurement also shows that MeV X-ray yield and temperature is largely insensitive to nanosecond laser contrasts up to 10−5. Also, preliminary measurements of similar MeV X-ray source using a double-foil scheme, where the laser-driven hot electrons from a thin foil undergoing relativistic transparency impinging onto a second high-Z converter foil separated by 50–400 m, show MeV X-ray yield more than an order of magnitude lower compared with the single-foil results.
Simulation models are used widely in pharmacology, epidemiology and health economics (HEs). However, there have been no attempts to incorporate models from these disciplines into a single integrated model. Accordingly, we explored this linkage to evaluate the epidemiological and economic impact of oseltamivir dose optimisation in supporting pandemic influenza planning in the USA. An HE decision analytic model was linked to a pharmacokinetic/pharmacodynamics (PK/PD) – dynamic transmission model simulating the impact of pandemic influenza with low virulence and low transmissibility and, high virulence and high transmissibility. The cost-utility analysis was from the payer and societal perspectives, comparing oseltamivir 75 and 150 mg twice daily (BID) to no treatment over a 1-year time horizon. Model parameters were derived from published studies. Outcomes were measured as cost per quality-adjusted life year (QALY) gained. Sensitivity analyses were performed to examine the integrated model's robustness. Under both pandemic scenarios, compared to no treatment, the use of oseltamivir 75 or 150 mg BID led to a significant reduction of influenza episodes and influenza-related deaths, translating to substantial savings of QALYs. Overall drug costs were offset by the reduction of both direct and indirect costs, making these two interventions cost-saving from both perspectives. The results were sensitive to the proportion of inpatient presentation at the emergency visit and patients’ quality of life. Integrating PK/PD–EPI/HE models is achievable. Whilst further refinement of this novel linkage model to more closely mimic the reality is needed, the current study has generated useful insights to support influenza pandemic planning.
The History, Electrocardiogram (ECG), Age, Risk Factors, and Troponin (HEART) score is a decision aid designed to risk stratify emergency department (ED) patients with acute chest pain. It has been validated for ED use, but it has yet to be evaluated in a prehospital setting.
A prehospital modified HEART score can predict major adverse cardiac events (MACE) among undifferentiated chest pain patients transported to the ED.
A retrospective cohort study of patients with chest pain transported by two county-based Emergency Medical Service (EMS) agencies to a tertiary care center was conducted. Adults without ST-elevation myocardial infarction (STEMI) were included. Inter-facility transfers and those without a prehospital 12-lead ECG or an ED troponin measurement were excluded. Modified HEART scores were calculated by study investigators using a standardized data collection tool for each patient. All MACE (death, myocardial infarction [MI], or coronary revascularization) were determined by record review at 30 days. The sensitivity and negative predictive values (NPVs) for MACE at 30 days were calculated.
Over the study period, 794 patients met inclusion criteria. A MACE at 30 days was present in 10.7% (85/794) of patients with 12 deaths (1.5%), 66 MIs (8.3%), and 12 coronary revascularizations without MI (1.5%). The modified HEART score identified 33.2% (264/794) of patients as low risk. Among low-risk patients, 1.9% (5/264) had MACE (two MIs and three revascularizations without MI). The sensitivity and NPV for 30-day MACE was 94.1% (95% CI, 86.8-98.1) and 98.1% (95% CI, 95.6-99.4), respectively.
Prehospital modified HEART scores have a high NPV for MACE at 30 days. A study in which prehospital providers prospectively apply this decision aid is warranted.
Whether monozygotic (MZ) and dizygotic (DZ) twins differ from each other in a variety of phenotypes is important for genetic twin modeling and for inferences made from twin studies in general. We analyzed whether there were differences in individual, maternal and paternal education between MZ and DZ twins in a large pooled dataset. Information was gathered on individual education for 218,362 adult twins from 27 twin cohorts (53% females; 39% MZ twins), and on maternal and paternal education for 147,315 and 143,056 twins respectively, from 28 twin cohorts (52% females; 38% MZ twins). Together, we had information on individual or parental education from 42 twin cohorts representing 19 countries. The original education classifications were transformed to education years and analyzed using linear regression models. Overall, MZ males had 0.26 (95% CI [0.21, 0.31]) years and MZ females 0.17 (95% CI [0.12, 0.21]) years longer education than DZ twins. The zygosity difference became smaller in more recent birth cohorts for both males and females. Parental education was somewhat longer for fathers of DZ twins in cohorts born in 1990–1999 (0.16 years, 95% CI [0.08, 0.25]) and 2000 or later (0.11 years, 95% CI [0.00, 0.22]), compared with fathers of MZ twins. The results show that the years of both individual and parental education are largely similar in MZ and DZ twins. We suggest that the socio-economic differences between MZ and DZ twins are so small that inferences based upon genetic modeling of twin data are not affected.
Population-based registries report 95% 5-year survival for children undergoing surgery for CHD. This study investigated paediatric cardiac surgical outcomes in the Australian indigenous population.
All children who underwent cardiac surgery between May, 2008 and August, 2014 were studied. Demographic information including socio-economic status, diagnoses and co-morbidities, and treatment and outcome data were collected at time of surgery and at last follow-up.
A total of 1528 children with a mean age 3.4±4.6 years were studied. Among them, 123 (8.1%) children were identified as indigenous, and 52.7% (62) of indigenous patients were in the lowest third of the socio-economic index compared with 28.2% (456) of non-indigenous patients (p⩽0.001). The indigenous sample had a significantly higher Comprehensive Aristotle Complexity score (indigenous 9.4±4.2 versus non-indigenous 8.7±3.9, p=0.04). The probability of having long-term follow-up did not differ between groups (indigenous 93.8% versus non-indigenous 95.6%, p=0.17). No difference was noted in 30-day mortality (indigenous 3.2% versus non-indigenous 1.4%, p=0.13). The 6-year survival for the entire cohort was 95.9%. The Cox survival analysis demonstrated higher 6-year mortality in the indigenous group – indigenous 8.1% versus non-indigenous 5.0%; hazard ratio (HR)=2.1; 95% confidence intervals (CI): 1.1, 4.2; p=0.03. Freedom from surgical re-intervention was 79%, and was not significantly associated with the indigenous status (HR=1.4; 95% CI: 0.9, 1.9; p=0.11). When long-term survival was adjusted for the Comprehensive Aristotle Complexity score, no difference in outcomes between the populations was demonstrated (HR=1.6; 95% CI: 0.8, 3.2; p=0.19).
The indigenous population experienced higher late mortality. This apparent relationship is explained by increased patient complexity, which may reflect negative social and environmental factors.
Cannabis use shows a robust dose-dependent relationship with psychosis risk among the general population. Despite this, it has been difficult to link cannabis use with risk for transitioning to a psychotic disorder among individuals at ultra-high risk (UHR) for psychosis. The present study examined UHR transition risk as a function of cannabis use characteristics which vary substantially between individuals including age of first use, cannabis abuse severity and a history of cannabis-induced attenuated psychotic symptoms (APS).
Participants were 190 UHR individuals (76 males) recruited at entry to treatment between 2000 and 2006. They completed a comprehensive baseline assessment including a survey of cannabis use characteristics during the period of heaviest use. Outcome was transition to a psychotic disorder, with mean time to follow-up of 5.0 years (range 2.4–8.7 years).
A history of cannabis abuse was reported in 58% of the sample. Of these, 26% reported a history of cannabis-induced APS. These individuals were 4.90 (95% confidence interval 1.93–12.44) times more likely to transition to a psychotic disorder (p = 0.001). Greater severity of cannabis abuse also predicted transition to psychosis (p = 0.036). However, this effect was mediated by higher abuse severity among individuals with a history of cannabis-induced APS.
Findings suggest that cannabis use poses risk in a subpopulation of UHR individuals who manifest cannabis-induced APS. Whether this reflects underlying genetic vulnerability requires further study. Nevertheless, findings reveal an important early marker of risk with potentially significant prognostic utility for UHR individuals.
It is well known that the cosmic ray intensity observed at the Earth's surface presents an 11 and 22-yr variations associated with the solar activity cycle. However, the observation and analysis of this modulation through ground muon detectors datahave been difficult due to the temperature effect. Furthermore, instrumental changes or temporary problems may difficult the analysis of these variations. In this work, we analyze the cosmic ray intensity observed since October 1970 until December 2012 by the Nagoya muon detector. We show the results obtained after analyzing all discontinuities and gaps present in this data and removing changes not related to natural phenomena. We also show the results found using the mass weighted method for eliminate the influence of atmospheric temperature changes on muon intensity observed at ground. As a preliminary result of our analyses, we show the solar cycle modulation in the muon intensity observed for more than 40 years.
Background: Epileptic encephalopathy (EE) is a severe condition in which epileptic activity itself may contribute to severe cognitive and behavioural impairments above and beyond what might be expected from the underlying pathology alone. Next generation sequencing technologies such as whole exome sequencing (WES) can detect underlying genetic causes of in EE. Methods: This report describes genotype-phenotype correlation of 29 subjects with unexplained epileptic encephalopathy, in whom WES, targeting a list of 557 epilepsy-associated genes was performed. Epilepsy phenotyping was done according to current ILAE recommendations. Results: Median age at seizure onset was 14 months (range 1-48). Electroclinical syndromes were applicable for 16/29, 8/16 had a definite/likely diagnosis. 6/8 subjects with West syndrome had variants in ALG13, STXBP1, PAFAH1B1, SLC35A2, CDKL5 and ADSL. 2 patients with Dravet syndrome had variants in SCN1A and PCDH19 respectively. 4/29 had unspecified EE and definite/likely diagnosis due to STXBP1, POLG, and KCNQ2 (2) variants. 4/29 had a possible diagnosis involving GABRB3, ARHGEF9, PCDH19 and SCN3A variants. Conclusions: The high diagnostic yield (definite/likely diagnosis in 11/29 = 38%), involving a broad variety of epilepsy-associated genes in different electroclinical syndromes justifies the diagnostic approach of early onset EE by next generation sequencing.
We describe bright microwave events that were first detected with the Parkes 64-m telescope at 8.4 or 22 GHz from six active-chromosphere stars. In some flares spectral data were obtained over a large frequency range from simultaneous measurements with the Parkes reflector (8.4 or 22 GHz), the Tidbinbilla interferometer (8.4 and 2.29 GHz), the Fleurs synthesis telescope (1.42 GHz) and the Molonglo Observatory synthesis telescope (0.843 GHz). Data on circular polarization were obtained from the Parkes observations at 8.4 GHz.
The stars were in a wide variety of evolutionary states, ranging from a single pre-main-sequence star (HD 36705), two RS CVn binaries (HD 127535, HD 128171), an Algol (HD 132742) and two apparently single K giants (HD 32918 and HD 196818). Their high brightness temperatures, positive spectral indices and low polarization are consistent with optically thick gyrosynchrotron emission from mildly relativistic electrons with average energies 0.5 to 3 MeV gyrating in inhomogeneous magnetic fields of 5 to 100 G.