For the last few decades, digital tools have become an important part of architectural design. Architectsand architecture students create their designs using one or more digital applications. Although most ofthese applications are advanced and can be used for various tasks – such as parametric design andbuilding performance simulations –, they lack some capabilities that are crucial to solving problems thatmight arise during the design and simulation process. Therefore, programming knowledge is invaluable tothose in the field of architecture for customizing digital applications to perform and automate tasks thatare out of the scope of built-in functions.In this research study, detailed examination of various case studies of custom-coded design programs isdiscussed. The programs written in Python proved to be crucial to organizing visual scripts by makingthem less confusing and more efficient. In addition to using computer programming within visual scriptingenvironments, this paper presents a case study of computer programs written in Python, JavaScript, andHTML that were used to organize an enormous amount of data produced by hundreds of glaresimulations. The custom programs performed the process of organizing, analyzing and visualizing largeamounts of data in a time-efficient manner, thereby facilitating informed decisions for better performativedesign.

The abundant use of solar panels in dense urban areas is causing severe visual discomfort because of thereflection of sunlight falling on their surfaces. These intense reflections can cause a disabling glare, whichimpairs the surrounding building occupants’ vision and hinders them from performing their daily tasks. Inorder to better predict glare caused by photovoltaics panels (PV) the research study will presentcomprehensive simulations to measure the amount of light reflected of PV arrays to accurately calculate theprobability of glare occurring on such case studies. Glare simulations will be conducted for every hour in theentire year. Additionally, detailed glare analysis will be performed by creating High Dynamic Range (HDR)renderings in multiple locations within an office building facing a building facade that is fitted with PVs.Subsequently, the simulation results will be statistically analysed to explore the effect of PVs on occupants’’visual comfort. A detailed conclusion of the outcome of the quantitative glare analysis will be introduced aswell as a brief discussion on future studies needed to improve visual comfort in dense urban areas

While COVID-19 lockdowns have slowed coronavirus transmission, such structural measures also have unintended consequences on mental and physical health. Growing evidence shows that exposure to the natural environment (e.g., blue-green spaces) can improve human health and wellbeing. In this narrative review, we synthesized the evidence about natures contributions to health and wellbeing during the first two years of the COVID-19 pandemic. We found that during the pandemic, people experienced multiple types of nature, including both outdoors and indoors. Frequency of visits to outdoor natural areas (i.e., public parks) depended on lockdown severity and socio-cultural contexts. Other forms of nature exposure, such as spending time in private gardens and viewing outdoor greenery from windows, may have increased. The majority of the evidence suggests nature exposure during COVID-19 pandemic was associated with less depression, anxiety, stress, and more happiness and life satisfaction. Additionally, nature exposure was correlated with less physical inactivity and fewer sleep disturbances. Evidence was mixed regarding associations between nature exposure and COVID-related health outcomes, while nature visits might be associated with greater rates of COVID-19 transmission and mortality when proper social distancing measures were not maintained. Findings on whether nature exposure during lockdowns helped ameliorate health inequities by impacting the health of lower-socioeconomic populations more than their higher-socioeconomic counterparts for example were mixed. Based on these findings, we argue that nature exposure may have buffered the negative mental and behavioral impacts of lockdowns during the COVID-19 pandemic. Recovery and resilience during the current crises and future public health crises might be improved with nature-based infrastructure, interventions, designs, and governance.

Despite the introduction of new therapies for multiple myeloma (MM), many patients are still dying from this disease and novel treatments are urgently needed. We have designed a novel hybrid molecule, called NEO214, that was generated by covalent conjugation of the natural monoterpene perillyl alcohol (POH), an inducer of endoplasmic reticulum (ER) stress, to rolipram (Rp), an inhibitor of phosphodiesterase-4 (PDE4). Its potential anticancer effects were investigated in a panel of MM cell lines. We found that NEO214 effectively killed MM cells in vitro with a potency that was over an order of magnitude stronger than that of its individual components, either alone or in combination. The cytotoxic mechanism of NEO214 involved severe ER stress and prolonged induction of CCAAT/enhancer-binding protein homologous protein (CHOP), a key pro-apoptotic component of the ER stress response. These effects were prevented by salubrinal, a pharmacologic inhibitor of ER stress, and by CHOP gene knockout. Conversely, combination of NEO214 with bortezomib, a drug in clinical use for patients with MM, resulted in synergistic enhancement of MM cell death. Combination with the adenylate cyclase stimulant forskolin did not enhance NEO214 impact, indicating that cyclic adenosine 3',5'-monophosphate (AMP) pathways might play a lesser role. Our study introduces the novel agent NEO214 as a potent inducer of ER stress with significant anti-MM activity in vitro. It should be further investigated as a potential MM therapy aimed at exploiting this tumor's distinct sensitivity to ER stress.

Previous experience has shown that transporting patients on extracorporeal membrane oxygenation (ECMO) is a safe and effective mode of transferring critically ill patients requiring maximum mechanical ventilator support to a quaternary care center. The coronavirus disease 2019 (COVID-19) pandemic posed new challenges. This is a multicenter, retrospective study of 113 patients with confirmed severe acute respiratory syndrome coronavirus 2, cannulated at an outside hospital and transported on ECMO to an ECMO center. This was performed by a multidisciplinary mobile ECMO team consisting of physicians for cannulation, critical care nurses, and an ECMO specialist or perfusionist, along with a driver or pilot. Teams practised strict airborne contact precautions with eyewear while caring for the patient and were in standard Personal Protective Equipment. The primary mode of transportation was ground. Ten patients were transported by air. The average distance traveled was 40 miles (SD ±56). The average duration of transport was 133 minutes (SD ±92). When stratified by mode of transport, the average distance traveled for ground transports was 36 miles (SD ±52) and duration was 136 minutes (SD ±93). For air, the average distance traveled was 66 miles (SD ±82) and duration was 104 minutes (SD ±70). There were no instances of transport-related adverse events including pump failures, cannulation complications at outside hospital, or accidental decannulations or dislodgements in transit. There were no instances of the transport team members contracting COVID-19 infection within 21 days after transport. By adhering to best practices and ACE precautions, patients with COVID-19 can be safely cannulated at an outside hospital and transported to a quaternary care center without increased risk to the transport team.

Background: Childhood vitamin A deficiency leads to increased morbidity and mortality. Human milk is the only source of vitamin A for exclusively breastfed infants. Dried Moringa oleifera leaf powder (moringa) is a good food source of provitamin A and other carotenoids. Its effect during lactation on human milk vitamin A and carotenoid content is unclear. Objectives: Our objective was to investigate the effect of maternal moringa consumption on human milk retinol and carotenoid concentrations and maternal and infant vitamin A status. Methods: We conducted a 3-month pilot single-blinded cluster-randomized controlled trial in breastfeeding mother-infant pairs (n = 50) in Kenya. Mothers received corn porridge with (20 g/d) or without moringa with complete breast expressions and maternal and infant serum collected at enrollment (infant <30 days old) and 3 months. Milk was analyzed for retinol and selected carotenoids; maternal/infant serum was analyzed for retinol binding protein (RBP). Results: 88% (n = 44) pairs completed milk and serum samples. Four mothers (9%) had vitamin A deficiency (RBP <0.07 µmol/L); 11 (25%) were vitamin A insufficient (VAI; RBP <1.05 µmol/L). Alpha-carotene concentration in milk was higher in the moringa than the control group at baseline (p = 0.024) and at exit (least squares means, LSM, 95%CI µg/mL 0.003, 0.003-0.004 moringa vs. 0.002, 0.001-0.003 control, n = 22/cluster; p = 0.014). In mothers with VAI, alpha-carotene was higher in the moringa group than controls at exit (LSM, 95%CI µg/mL 0.005, 0.003-0.009 moringa, n = 3, vs. 0.002, 0.000-0.004 control, n = 8, p = 0.027) with no difference at baseline. Milk carotenoids did not correlate with vitamin A status (serum RBP) in infants or mothers. Conclusions: Maternal moringa consumption did not impact concentration of milk vitamin A and resulted in limited increase in milk carotenoids in this cohort.

BACKGROUND: The Colombian population, as well as those in other Latin American regions, arose from a recent tri-continental admixture among Native Americans, Spanish invaders, and enslaved Africans, all of whom passed through a population bottleneck due to widespread infectious diseases that left small isolated local settlements. As a result, the current population reflects multiple founder effects derived from diverse ancestries. METHODS: We characterized the role of admixture and founder effects on the origination of the mutational landscape that led to neurodegenerative disorders under these historical circumstances. Genomes from 900 Colombian individuals with Alzheimers disease (AD) [n = 376], frontotemporal lobar degeneration-motor neuron disease continuum (FTLD-MND) [n = 197], early-onset dementia not otherwise specified (EOD) [n = 73], and healthy participants [n = 254] were analyzed. We examined their global and local ancestry proportions and screened this cohort for deleterious variants in disease-causing and risk-conferring genes. RESULTS: We identified 21 pathogenic variants in AD-FTLD related genes, and PSEN1 harbored the majority (11 pathogenic variants). Variants were identified from all three continental ancestries. TREM2 heterozygous and homozygous variants were the most common among AD risk genes (102 carriers), a point of interest because the disease risk conferred by these variants differed according to ancestry. Several gene variants that have a known association with MND in European populations had FTLD phenotypes on a Native American haplotype. Consistent with founder effects, identity by descent among carriers of the same variant was frequent. CONCLUSIONS: Colombian demography with multiple mini-bottlenecks probably enhanced the detection of founder events and left a proportionally higher frequency of rare variants derived from the ancestral populations. These findings demonstrate the role of genomically defined ancestry in phenotypic disease expression, a phenotypic range of different rare mutations in the same gene, and further emphasize the importance of inclusiveness in genetic studies.

Giant congenital melanocytic nevi are NRAS-driven proliferations that may cover up to 80% of the body surface. Their most dangerous consequence is progression to melanoma. This risk often triggers preemptive extensive surgical excisions in childhood, producing severe lifelong challenges. We have presented preclinical models, including multiple genetically engineered mice and xenografted human lesions, which enabled testing locally applied pharmacologic agents to avoid surgery. The murine models permitted the identification of proliferative versus senescent nevus phases and treatments targeting both. These nevi recapitulated the histologic and molecular features of human giant congenital nevi, including the risk of melanoma transformation. Cutaneously delivered MEK, PI3K, and c-KIT inhibitors or proinflammatory squaric acid dibutylester (SADBE) achieved major regressions. SADBE triggered innate immunity that ablated detectable nevocytes, fully prevented melanoma, and regressed human giant nevus xenografts. These findings reveal nevus mechanistic vulnerabilities and suggest opportunities for topical interventions that may alter the therapeutic options for children with congenital giant nevi.

Background

Child health is a key priority on the global health agenda, yet the provision of essential and emergency surgery in children is patchy in resource-poor regions. This study was aimed to determine the mortality risk for emergency abdominal paediatric surgery in low-income countries globally.

Methods

Multicentre, international, prospective, cohort study. Self-selected surgical units performing emergency abdominal surgery submitted prespecified data for consecutive children aged <16 years during a 2-week period between July and December 2014. The United Nation's Human Development Index (HDI) was used to stratify countries. The main outcome measure was 30-day postoperative mortality, analysed by multilevel logistic regression.

Results

This study included 1409 patients from 253 centres in 43 countries; 282 children were under 2 years of age. Among them, 265 (18.8%) were from low-HDI, 450 (31.9%) from middle-HDI and 694 (49.3%) from high-HDI countries. The most common operations performed were appendectomy, small bowel resection, pyloromyotomy and correction of intussusception. After adjustment for patient and hospital risk factors, child mortality at 30 days was significantly higher in low-HDI (adjusted OR 7.14 (95% CI 2.52 to 20.23), p<0.001) and middle-HDI (4.42 (1.44 to 13.56), p=0.009) countries compared with high-HDI countries, translating to 40 excess deaths per 1000 procedures performed.

Conclusions

Adjusted mortality in children following emergency abdominal surgery may be as high as 7 times greater in low-HDI and middle-HDI countries compared with high-HDI countries. Effective provision of emergency essential surgery should be a key priority for global child health agendas.

Trial registration number

NCT02179112; Pre-results.