A rapid method for optimization of the rocket propulsion system for single-stage-to-orbit vehicles

A rapid analytical method for the optimization of rocket propulsion systems is presented for a vertical take-off, horizontal landing, single-stage-to-orbit launch vehicle. This method utilizes trade-offs between propulsion characteristics affecting flight performance and engine system mass. The performance results from a point-mass trajectory optimization program are combined with a linearized sizing program to establish vehicle sizing trends caused by propulsion system variations. The linearized sizing technique was developed for the class of vehicle systems studied herein. The specific examples treated are the optimization of nozzle expansion ratio and lift-off thrust-to-weight ratio to achieve either minimum gross mass or minimum dry mass. Assumed propulsion system characteristics are high chamber pressure, liquid oxygen and liquid hydrogen propellants, conventional bell nozzles, and the same fixed nozzle expansion ratio for all engines on a vehicle

The impact of COVID‐19 in Dravet syndrome: A UK survey

OBJECTIVES: To understand the risks, impact and outcome of COVID-19 in people affected by Dravet Syndrome (DS). MATERIALS AND METHODS: An anonymous cross-sectional online survey was conducted between June 17 and July 13, 2020, addressed to families of people with DS. RESULTS: A total of 116 responses were collected, from families of children (n = 86; 74%) and adults (30; 26%) with DS. The majority (106; 91%) were shielded at the family home during lockdown. Symptoms compatible with COVID-19 were reported in 22 (19%) individuals. Only four individuals with symptoms had a PCR swab test, none of which was positive. Only one symptomatic person had antibody testing (but not swab testing), which was positive. One person had repeatedly positive swab tests whilst in hospital for renal failure, but had no typical symptoms of COVID-19. In 50% of people with DS who developed possible or probable COVID-19 symptoms, seizure worsening was reported, in terms of increased seizure frequency or duration or both. Medical attention was required in 9/22 (41%), all of whom were children. CONCLUSIONS: In this cohort of people with DS, we observed an infection rate, determined by compatible symptoms, of 19%, with no deaths and benign outcome in most cases despite the underlying complex epilepsy although children often required medical attention. Early adoption of preventative measures, including testing of symptomatic individuals, regular surveillance for people living in residential care facilities, and shielding of individuals with comorbidities increasing the risk of severe outcome, may limit the impact of COVID-19

The impact of SARS-CoV-2 vaccination in Dravet Syndrome: A UK survey

Background: The COVID-19 pandemic led to the urgent need for accelerated vaccine development. Approved vaccines have proved to be safe and well tolerated across millions of people in the general population. Dravet Syndrome (DS) is a severe, early onset, developmental and epileptic encephalopathy. Vaccination is a precipitating factor for seizures. Whilst there is no evidence that vaccine-precipitated seizures lead to adverse outcomes in people with DS, fear surrounding vaccination can remain for caregivers of people with DS, in some cases resulting in rejection of recommended vaccinations, leaving individuals more vulnerable to the relevant infections. A greater understanding of the safety profile of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) vaccination in this vulnerable group will help provide guidance for caregivers and clinicians when considering vaccination. / Methods: A cross‐sectional survey regarding COVID-19 and SARS-CoV-2 vaccine, in people with DS, was conducted by Dravet Syndrome UK (DSUK). Concomitantly, a review of individuals with DS who had recently received the SARS-CoV-2 vaccine, and who are resident at the Chalfont Centre for Epilepsy (CCE), or attend epilepsy clinics at the National Hospital for Neurology and Neurosurgery (NHNN), was undertaken. / Results: 38 people completed the DSUK survey. 37% of caregivers reported being concerned about someone with DS receiving the SARS-CoV-2 vaccine; with some reporting that they would decline a vaccine when offered. 77% had not received any advice from a health care professional about the SARS-CoV-2 vaccination. 18/38 were eligible for SARS-CoV-2 vaccination, of whom nine had received their first vaccine dose. Combining the results of the DSUK survey and the review of individuals monitored at CCE or NHNN, fifteen people with DS had received their first dose of the SARS-CoV-2 vaccine. 11/15 (73%) reported at least one side effect, the most common being fatigue (6/15; 40%) and fever (6/15; 40%). Three individuals (20%) reported an increase in seizure frequency after the first vaccine dose. No increase in seizure frequency or duration was reported after the second dose. / Conclusion: Overall, these results suggest that SARS-CoV-2 vaccines are safe and well tolerated in individuals with DS, as they are in most people without DS. In most people with DS, SARS-CoV-2 vaccine does not appear to be associated with an increase in the frequency or duration of seizures, even in those who develop fever post-vaccination. Many caregivers are concerned about a person with DS receiving a SARS-CoV-2 vaccine, with some reporting that they would decline a SARS-CoV-2 vaccine when offered. It is crucial that healthcare professionals are proactive in providing accurate information regarding the risks and benefits of vaccination in this population, given the potential for serious outcomes from infection

Using random forest and decision tree models for a new vehicle prediction approach in computational toxicology

yesDrug vehicles are chemical carriers that provide beneficial aid to the drugs they bear. Taking advantage of their favourable properties can potentially allow the safer use of drugs that are considered highly toxic. A means for vehicle selection without experimental trial would therefore be of benefit in saving time and money for the industry. Although machine learning is increasingly used in predictive toxicology, to our knowledge there is no reported work in using machine learning techniques to model drug-vehicle relationships for vehicle selection to minimise toxicity. In this paper we demonstrate the use of data mining and machine learning techniques to process, extract and build models based on classifiers (decision trees and random forests) that allow us to predict which vehicle would be most suited to reduce a drug’s toxicity. Using data acquired from the National Institute of Health’s (NIH) Developmental Therapeutics Program (DTP) we propose a methodology using an area under a curve (AUC) approach that allows us to distinguish which vehicle provides the best toxicity profile for a drug and build classification models based on this knowledge. Our results show that we can achieve prediction accuracies of 80 % using random forest models whilst the decision tree models produce accuracies in the 70 % region. We consider our methodology widely applicable within the scientific domain and beyond for comprehensively building classification models for the comparison of functional relationships between two variables

Prostate imaging features that indicate benign or malignant pathology on biopsy

Accurate diagnosis of clinically significant prostate cancer is essential in identifying patients who should be offered treatment with curative intent. Modifications to the Gleason grading system in recent years show that accurate grading and reporting at needle biopsy can improve identification of clinically significant prostate cancers. Extracapsular extension of prostate cancer has been demonstrated to be an adverse prognostic factor with greater risk of metastatic spread than organ-confined disease. Tumor volume may be an independent prognostic factor and should be considered in conjunction with other factors. Multiparametric magnetic resonance imaging (MP-MRI) has become an increasingly important tool in the diagnosis and characterization of prostate cancer. MP-MRI allows T2-weighted (T2W) anatomical imaging to be combined with functional and physiological assessment. Diffusion-weighted imaging (DWI) has shown greater sensitivity, specificity and negative predictive value compared to prostate specific antigen (PSA) testing and T2W imaging alone and has a more positive correlation with Gleason score and tumour volume. Dynamic gadolinium contrast-enhanced (DCE) imaging can exhibit difficulties in distinguishing prostatitis from Malignancy in the peripheral zone, and between benign prostatic hyperplasia (BPH) and Malignancies in the transition zone (TZ). Computer aided diagnosis utilizes software to aid radiologists in detecting and diagnosing Abnormalities from diagnostic imaging. New techniques of quantitative MRI, such as VERDICT MRI use tissue-specific factors to delineate different cellular and microstructural phenotypes, characterizing tissue properties with greater detail. Proton MR spectroscopic imaging (MRSI) is a more technically challenging imaging modality than DCE and DWI MRI. Over the last decade, choline and prostate-specific membrane antigen (PSMA) positron emission tomography (PET) have developed as better tools for staging than conventional imaging. While hyperpolarized MRI shows promise in improving the imaging and differentiation of benign and Malignant lesions there is further work required. Accurate reading and interpretation of diagnostic investigations is key to accurate identification of abnormal areas requiring biopsy, sparing those in whom benign or indolent disease can be managed by non-invasive means. Embracing and advancing existing technologies is essential in furthering this process

Sulforaphane promotes ER stress, autophagy and cell death: implications for cataract surgery

Posterior capsule opacification (PCO) commonly develops following cataract surgery and is a wound-healing response that can ultimately lead to secondary visual loss. Improved management of this problem is required. The isothiocyanate, sulforaphane (SFN) is reported to exert cytoprotective and cytotoxic actions and the latter may be exploited to treat/prevent PCO. SFN concentrations of 10µM and above significantly impaired wound-healing in a human lens capsular bag model. A similar pattern of response was also seen with a human lens cell line, FHL124. SFN treatment promoted increased expression of ER stress genes, which also corresponded with protein expression. Evidence of autophagy was observed in response to SFN as determined by increased LC3-II levels and detection of autophagic vesicles. This response was disrupted by established autophagy inhibitors chloroquine and 3-MA. SFN was found to promote MAPK signaling and inhibition of ERK activation using U0126 prevented SFN induced LC3-II elevation and vesicle formation. SFN also significantly increased levels of reactive oxygen species. Taken together, our findings suggest that SFN is capable of reducing lens cell growth and viability and thus could serve as a putative therapeutic agent for PCO

A prospective analysis of robotic targeted MRI-US fusion prostate biopsy using the centroid targeting approach

Robotic prostate biopsy is an emerging technology. Recent development of this tool has allowed the performance of a transperineal prostate biopsy allowing pre-programmed standardized biopsy schemes. Prospective data collection was undertaken in 86 consecutive men who underwent robotically assisted transperineal prostate biopsy. All underwent a multi-parametric MRI pre-biopsy with centroid targeting followed by systematic template prostate biopsy. For the purposes of this study, our definition of clinically significant prostate cancer (csPCa) is any Gleason score > 6. Mean (SD) age, median (IQR) PSA, and median (IQR) prostate volume were 64.24 (6.97) years, of 7.79 ng/ml (6.5) and 45.06 cc (28), respectively. Overall, 44 (51.2%) men were diagnosed with csPCa. csPCa was detected in the targeted biopsies alone in 35 (40.1%) men. The addition of the 12-zone template biopsy increased the yield of csPCa for another 9 (10.5%) men. Of these 9 men, the majority (7) harbored primary pattern 3 disease and only 1 was identified to have high-grade disease. Out of these 9 men, 7 of them had the identification of csPCa in the sector, where a target was contained within that zone. Robotic-assisted prostate biopsy in our study has demonstrated a high detection of csPCa when combined with limited near-field sampling. Our study suggests the use of more accurate biopsy schemes such as ring-targeting of lesions to mitigate against systematic and random mathematical errors. Adoption of this tool and biopsy strategy would potentially avoid the increased morbidity associated with whole gland systematic unguided biopsies

Locating mathematics within post-16 vocational education in England

The political importance of mathematics in post-16 education is clear. Far less clear is how mathematics does and should relate to vocational education. Successive mathematics curricula (e.g. core skills, key skills) have been developed in England with vocational learners in mind. Meanwhile, general mathematics qualifications remain largely disconnected from vocational learning. Following a brief historical survey of mathematics within vocational education, the paper presents findings from a nested case study of student groups in three large Further Education colleges in England. The primary unit of analysis herein is student groups learning Functional Mathematics in two vocational areas: construction and hairdressing. We show how approaches to organising teaching, developing connected curricula and classroom pedagogy tend to isolate or integrate mathematics from/with the vocational experience. Integrated approaches are shown to impact positively on student engagement and attitudes to learning mathematics. The paper concludes by discussing the potential impact of academic qualifications displacing vocationally relevant mathematics

1967: Abilene Christian College Bible Lectures - Full Text

LIFTING UP THE CHRIST” Being the Abilene Christian College Annual Bible Lectures 1967 $3.95 Published by ABILENE CHRISTIAN COLLEGE STUDENTS EXCHANGE ACC Station Abilene, Texa

Expression of UV-Sensitive Parapinopsin in the Iguana Parietal Eyes and Its Implication in UV-Sensitivity in Vertebrate Pineal-Related Organs

The pineal-related organs of lower vertebrates have the ability to discriminate different wavelengths of light. This wavelength discrimination is achieved through antagonistic light responses to UV or blue and visible light. Previously, we demonstrated that parapinopsin underlies the UV reception in the lamprey pineal organ and identified parapinopsin genes in teleosts and frogs of which the pineal-related organs were reported to discriminate light. In this study, we report the first identification of parapinopsin in the reptile lineage and show its expression in the parietal eye of the green iguana. Spectroscopic analysis revealed that iguana parapinopsin is a UV-sensitive pigment, similar to lamprey parapinopsin. Interestingly, immunohistochemical analyses using antibodies specific to parapinopsin and parietopsin, a parietal eye green-sensitive pigment, revealed that parapinopsin and parietopsin are colocalized in the outer segments of the parietal eye photoreceptor cells in iguanas. These results strongly suggest that parapinopsin underlies the wavelength discrimination involving UV reception in the iguana parietal eye. The current findings support the idea that parapinopsin is a common photopigment underlying the UV-sensitivity in wavelength discrimination of the pineal-related organs found from lampreys to reptiles