Face editing with GAN -- A Review

In recent years, Generative Adversarial Networks (GANs) have become a hot topic among researchers and engineers that work with deep learning. It has been a ground-breaking technique which can generate new pieces of content of data in a consistent way. The topic of GANs has exploded in popularity due to its applicability in fields like image generation and synthesis, and music production and composition. GANs have two competing neural networks: a generator and a discriminator. The generator is used to produce new samples or pieces of content, while the discriminator is used to recognize whether the piece of content is real or generated. What makes it different from other generative models is its ability to learn unlabeled samples. In this review paper, we will discuss the evolution of GANs, several improvements proposed by the authors and a brief comparison between the different models. Index Terms generative adversarial networks, unsupervised learning, deep learning

A systems approach to sustainability in space

Man has been fascinated by space since the beginning of civilization. There have been major advancements made in this field over many years. But if history has been witness to anything, it is that, for every advancement we’ve made, we’ve left something behind. Space missions over the past many decades have left behind over 7500 tonnes of debris in orbit. But it is still a problem which is out of sight, hence out of mind. There are millions of objects in space, most of which are too small to be able to track. Recent trends show that the number of launches are increasing each year. Thus, the amount of debris is only going to increase. This problem is a complex one since space is a global resource, and there is no central authority to keep a check on it. Satellites play such an important role in all aspects of our lives, that a threat to them is a threat to our current way of life. Over the years, there have been inter country disputes, increased tensions and unchecked misuse of space. The president of United States recently announced that Space is a place for war. If this problem is to be solved, there has to be cooperation at a global scale. Major policy changes and space laws need to be implemented in this field, along with co-operation on a large scale. Fifty years back, everyone was dumping plastic into the oceans, thinking that they were so large that a few bottles won’t make a difference. Now, there are huge islands of ocean plastic floating in the Pacific. Space debris is very similar to this problem, and we are at the advantage of not having gone too far yet. As designers, we may not have all the answers, but we can ask the right questions. Systems thinking allows us to associate seemingly unrelated aspects of the problem, and connect people from different fields. We have the advantage of looking at the entire picture in a holistic and unbiased way. A problem as complex as this needs intervention at multiple levels. It is a problem that is going to have major repercussions in the coming years, and needs foresight, which we attempt to add through this project. Through this project, we are expanding the boundaries of design. Design thinking is rarely used in the space industry and employing it on a system level is what is needed to solve the problem of space debris. As part of the project, we met with professionals, engineering students, policy makers, academicians and researchers. We organised co-creation workshops with school kids as well as scientists at the Indian Space Research Organisation (ISRO). Dividing the scientists into groups based on temporal scenarios, such as ‘past’, ‘present’ and ‘future’, we came up with diverse solutions. We drew connections at each stage. We translated the raw ideas that kids came up with to tackle space debris into feasible solutions, using scientists’ expertise. We collated data from multiple primary, first hand sources and used it to come up with solutions. Due to the importance of policies in solving a problem as huge as space debris, we developed a first draft of a national policy for space debris. The policy lays down the guidelines to be followed by any space agency operating within the country. It also proposes maintaining a registry of space objects in orbit. It suggests a method to carry out threat assessment of a particular space debris. We also introduced a credit system for all space operators within India. This policy not only regulates private and public parties of the space industry, but also give guidelines for possible future scenarios. A major aspect of space debris as a problem is that relatively less people know about it. Even within the science community, many people know about the problem, but aren’t working towards it. There is a need for awareness among the masses. The more people know and understand the problem, the more brains working towards it. As designers, we can act as facilitators to promote awareness and dialogue about the topic. To do this, we developed the character of ‘Satellite girl’ and made a comic series, showing the effects of Kessler’s syndrome and how it can devastate the 21st century world. We developed two directions of speculative scenarios; A utopian future showing how global cooperation can bring about a positive change for mankind through space technology, and a dystopian future, that shows the after effects of a Kessler’s syndrome. The final systems intervention in the subject was in the form of solutions. Talking to people, employing co-design methodologies and iterating on ideas helped us to come up with potential solutions to help tackle space debris. These solutions could be as basic as redesigning a satellite to as complex as changing the whole system of how we launch and collect satellites. This is an ongoing project, and we hope to use systems thinking in more innovative ways to tackle this issue on multiple levels. We plan to pitch our policy draft to law experts, our ideas to ISRO and our awareness campaigns to publishing houses. We will be following up on our previous stakeholders and constantly contacting many more. We also intend to propose a Life Cycle Assessment (LCA) model for space flights. We would like to visualize all the different aspects of Space and sustainability and make people aware about the problem at hand. We want to create a common platform for people from different expertise levels to come together to solve this wicked problem. Democratization of space is something that our project also has in mind. We hope that this project will give enough clarity and push to the right people in the right direction, so that we can start working towards solving the issue. By clearly stating the future steps and sustainability opportunities, we hope to not repeat our past mistakes

Molecular diagnostic yield of exome sequencing in patients with congenital hydrocephalus: A systematic review and meta-analysis

IMPORTANCE: Exome sequencing (ES) has been established as the preferred first line of diagnostic testing for certain neurodevelopmental disorders, such as global developmental delay and autism spectrum disorder; however, current recommendations are not specific to or inclusive of congenital hydrocephalus (CH). OBJECTIVE: To determine the diagnostic yield of ES in CH and whether ES should be considered as a first line diagnostic test for CH. DATA SOURCES: PubMed, Cochrane Library, and Google Scholar were used to identify studies published in English between January 1, 2010, and April 10, 2023. The following search terms were used to identify studies: congenital hydrocephalus, ventriculomegaly, cerebral ventriculomegaly, primary ventriculomegaly, fetal ventriculomegaly, prenatal ventriculomegaly, molecular analysis, genetic cause, genetic etiology, genetic testing, exome sequencing, whole exome sequencing, genome sequencing, microarray, microarray analysis, and copy number variants. STUDY SELECTION: Eligible studies included those with at least 10 probands with the defining feature of CH and/or severe cerebral ventriculomegaly that had undergone ES. Studies with fewer than 10 probands, studies of mild or moderate ventriculomegaly, and studies using genetic tests other than ES were excluded. A full-text review of 68 studies was conducted by 2 reviewers. Discrepancies were resolved by consensus. DATA EXTRACTION AND SYNTHESIS: Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines and Meta-Analysis of Observational Studies in Epidemiology guidelines were used by 2 reviewers to extract data. Data were synthesized using a random-effects model of single proportions. Data analysis occurred in April 2023. MAIN OUTCOMES AND MEASURES: The primary outcome was pooled diagnostic yield. Additional diagnostic yields were estimated for specific subgroups on the basis of clinical features, syndromic presentation, and parental consanguinity. For each outcome, a 95% CI and estimate of interstudy heterogeneity (I2 statistic) was reported. RESULTS: From 498 deduplicated and screened records, 9 studies with a total of 538 CH probands were selected for final inclusion. The overall diagnostic yield was 37.9% (95% CI, 20.0%-57.4%; I2 = 90.1). The yield was lower for isolated and/or nonsyndromic cases (21.3%; 95% CI, 12.8%-31.0%; I2 = 55.7). The yield was higher for probands with reported consanguinity (76.3%; 95% CI, 65.1%-86.1%; I2 = 0) than those without (16.2%; 95% CI, 12.2%-20.5%; I2 = 0). CONCLUSIONS AND RELEVANCE: In this systematic review and meta-analysis of the diagnostic yield of ES in CH, the diagnostic yield was concordant with that of previous recommendations for other neurodevelopmental disorders, suggesting that ES should also be recommended as a routine diagnostic adjunct for patients with CH

Using Electronic Health Records to Characterize Prescription Patterns: Focus on Antidepressants in Nonpsychiatric Outpatient Settings

Objective To characterize nonpsychiatric prescription patterns of antidepressants according to drug labels and evidence assessments (on-label, evidence-based, and off-label) using structured outpatient electronic health record (EHR) data. Methods A retrospective analysis was conducted using deidentified EHR data from an outpatient practice at a New York City-based academic medical center. Structured “medication–diagnosis” pairs for antidepressants from 35 325 patients between January 2010 and December 2015 were compared to the latest drug product labels and evidence assessments. Results Of 140 929 antidepressant prescriptions prescribed by primary care providers (PCPs) and nonpsychiatry specialists, 69% were characterized as “on-label/evidence-based uses.” Depression diagnoses were associated with 67 233 (48%) prescriptions in this study, while pain diagnoses were slightly less common (35%). Manual chart review of “off-label use” prescriptions revealed that on-label/evidence-based diagnoses of depression (39%), anxiety (25%), insomnia (13%), mood disorders (7%), and neuropathic pain (5%) were frequently cited as prescription indication despite lacking ICD-9/10 documentation. Conclusions The results indicate that antidepressants may be prescribed for off-label uses, by PCPs and nonpsychiatry specialists, less frequently than believed. This study also points to the fact that there are a number of off-label uses that are efficacious and widely accepted by expert clinical opinion but have not been included in drug compendia. Despite the fact that diagnosis codes in the outpatient setting are notoriously inaccurate, our approach demonstrates that the correct codes are often documented in a patient’s recent diagnosis history. Examining both structured and unstructured data will help to further validate findings. Routinely collected clinical data in EHRs can serve as an important resource for future studies in investigating prescribing behaviors in outpatient clinics

A phase-I trial of pre-operative, margin intensive, stereotactic body radiation therapy for pancreatic cancer: the 'SPARC' trial protocol.

BACKGROUND: Standard therapy for borderline-resectable pancreatic cancer in the UK is surgery with adjuvant chemotherapy, but rates of resection with clear margins are unsatisfactory and overall survival remains poor. Meta-analysis of single-arm studies shows the potential of neo-adjuvant chemo-radiotherapy but the relative radio-resistance of pancreatic cancer means the efficacy of conventional dose schedules is limited. Stereotactic radiotherapy achieves sufficient accuracy and precision to enable pre-operative margin-intensive dose escalation with the goal of increasing rates of clear resection margins and local disease control. METHODS/DESIGN: SPARC is a "rolling-six" design single-arm study to establish the maximum tolerated dose for margin-intensive stereotactic radiotherapy before resection of pancreatic cancer at high risk of positive resection margins. Eligible patients will have histologically or cytologically proven pancreatic cancer defined as borderline-resectable per National Comprehensive Cancer Network criteria or operable tumour in contact with vessels increasing the risk of positive margin. Up to 24 patients will be recruited from up to 5 treating centres and a 'rolling-six' design is utilised to minimise delays and facilitate ongoing recruitment during dose-escalation. Radiotherapy will be delivered in 5 daily fractions and surgery, if appropriate, will take place 5-6 weeks after radiotherapy. The margin-intense radiotherapy concept includes a systematic method to define the target volume for a simultaneous integrated boost in the region of tumour-vessel infiltration, and up to 4 radiotherapy dose levels will be investigated. Maximum tolerated dose is defined as the highest dose at which no more than 1 of 6 patients or 0 of 3 patients experience a dose limiting toxicity. Secondary endpoints include resection rate, resection margin status, response rate, overall survival and progression free survival at 12 and 24 months. Translational work will involve exploratory analyses of the cytological and humoral immunological responses to stereotactic radiotherapy in pancreatic cancer. Radiotherapy quality assurance of target definition and radiotherapy planning is enforced with pre-trial test cases and on-trial review. Recruitment began in April 2015. DISCUSSION: This prospective multi-centre study aims to establish the maximum tolerated dose of pre-operative margin-intensified stereotactic radiotherapy in pancreatic cancer at high risk of positive resection margins with a view to subsequent definitive comparison with other neoadjuvant treatment options

Guinea pig models for translation of the developmental origins of health and disease hypothesis into the clinic

Over 30 years ago Professor David Barker first proposed the theory that events in early life could explain an individual\u27s risk of non-communicable disease in later life: the developmental origins of health and disease (DOHaD) hypothesis. During the 1990s the validity of the DOHaD hypothesis was extensively tested in a number of human populations and the mechanisms underpinning it characterised in a range of experimental animal models. Over the past decade, researchers have sought to use this mechanistic understanding of DOHaD to develop therapeutic interventions during pregnancy and early life to improve adult health. A variety of animal models have been used to develop and evaluate interventions, each with strengths and limitations. It is becoming apparent that effective translational research requires that the animal paradigm selected mirrors the tempo of human fetal growth and development as closely as possible so that the effect of a perinatal insult and/or therapeutic intervention can be fully assessed. The guinea pig is one such animal model that over the past two decades has demonstrated itself to be a very useful platform for these important reproductive studies. This review highlights similarities in the in utero development between humans and guinea pigs, the strengths and limitations of the guinea pig as an experimental model of DOHaD and the guinea pig\u27s potential to enhance clinical therapeutic innovation to improve human health. (Figure presented.)

Durability of high-frequency 10-kHz spinal cord stimulation for patients with painful diabetic neuropathy refractory to conventional treatments: 12-month results from a randomized controlled trial

No abstract available

A randomized controlled trial of high frequency (10 kHz) spinal cord stimulation in painful diabetic neuropathy

Importance: Many patients with diabetic peripheral neuropathy experience chronic pain and inadequate relief despite best available medical treatments. Objective: To determine whether 10-kHz spinal cord stimulation (SCS) improves outcomes for patients with refractory painful diabetic neuropathy (PDN). Design, Setting, and Participants: The prospective, multicenter, open-label SENZA-PDN randomized clinical trial compared conventional medical management (CMM) with 10-kHz SCS plus CMM. Participants with PDN for 1 year or more refractory to gabapentinoids and at least 1 other analgesic class, lower limb pain intensity of 5 cm or more on a 10-cm visual analogue scale (VAS), body mass index (calculated as weight in kilograms divided by height in meters squared) of 45 or less, hemoglobin A1c (HbA1c) of 10% or less, daily morphine equivalents of 120 mg or less, and medically appropriate for the procedure were recruited from clinic patient populations and digital advertising. Participants were enrolled from multiple sites across the US, including academic centers and community pain clinics, between August 2017 and August 2019 with 6-month follow-up and optional crossover at 6 months. Screening 430 patients resulted in 214 who were excluded or declined participation and 216 who were randomized. At 6-month follow-up, 187 patients were evaluated. Interventions: Implanted medical device delivering 10-kHz SCS. Main Outcomes and Measures: The prespecified primary end point was percentage of participants with 50% pain relief or more on VAS without worsening of baseline neurological deficits at 3 months. Secondary end points were tested hierarchically, as prespecified in the analysis plan. Measures included pain VAS, neurological examination, health-related quality of life (EuroQol Five-Dimension questionnaire), and HbA1c over 6 months. Results: Of 216 randomized patients, 136 (63.0%) were male, and the mean (SD) age was 60.8 (10.7) years. Additionally, the median (interquartile range) duration of diabetes and peripheral neuropathy were 10.9 (6.3-16.4) years and 5.6 (3.0-10.1) years, respectively. The primary end point assessed in the intention-to-treat population was met by 5 of 94 patients in the CMM group (5%) and 75 of 95 patients in the 10-kHz SCS plus CMM group (79%; difference, 73.6%; 95% CI, 64.2-83.0; P < .001). Infections requiring device explant occurred in 2 patients in the 10-kHz SCS plus CMM group (2%). For the CMM group, the mean pain VAS score was 7.0 cm (95% CI, 6.7-7.3) at baseline and 6.9 cm (95% CI, 6.5-7.3) at 6 months. For the 10-kHz SCS plus CMM group, the mean pain VAS score was 7.6 cm (95% CI, 7.3-7.9) at baseline and 1.7 cm (95% CI, 1.3-2.1) at 6 months. Investigators observed neurological examination improvements for 3 of 92 patients in the CMM group (3%) and 52 of 84 in the 10-kHz SCS plus CMM group (62%) at 6 months (difference, 58.6%; 95% CI, 47.6-69.6; P < .001). Conclusions and Relevance: Substantial pain relief and improved health-related quality of life sustained over 6 months demonstrates 10-kHz SCS can safely and effectively treat patients with refractory PDN. Trial Registration: ClincalTrials.gov Identifier: NCT0322842

Meiotic recombination gets stressed out: CO frequency is plastic under pressure

Meiotic recombination ensures the fertility of gametes and creates novel genetic combinations. Although meiotic crossover (CO) frequency is under homeostatic control, CO frequency is also plastic in nature and can respond to environmental conditions. Most investigations have focused on temperature and recombination, but other external and internal stimuli also have important roles in modulating CO frequency. Even less is understood about the molecular mechanisms that underly these phenomenon, but recent work has begun to advance our knowledge in this field. In this review, we identify and explore potential mechanisms including changes in: the synaptonemal complex, chromatin state, DNA methylation, and RNA splicing