Effectiveness of immune checkpoint inhibitor therapy on bone metastases in non-small-cell lung cancer.

Background: Bone metastases (BoMs) are prevalent in patients with metastatic non-small-cell lung cancer (NSCLC) however, there are limited data detailing how BoMs respond to immune checkpoint inhibitors (ICIs). The purpose of this study was to compare the imaging response to ICIs of BoMs against visceral metastases and to evaluate the effect of BoMs on survival. Materials and methods: A retrospective, multicentre cohort study was conducted in patients with NSCLC treated with nivolumab or pembrolizumab in Alberta, Canada from 2015 to 2020. The primary endpoint was the real-world organ specific progression free survival (osPFS) of bone versus visceral metastases. Visceral metastases were categorized as adrenal, brain, liver, lung, lymph node, or other intra-abdominal lesions. The secondary outcome was overall survival (OS) amongst patients with and without BoMs. Results: A total of 573 patients were included of which all patients had visceral metastases and 243 patients (42.4%) had BoMs. High PD-L1 expression was identified in 268 patients (46.8%). No significant difference in osPFS was observed between bone, liver, and intra-abdominal metastases (p=0.20 and p=0.76, respectively), with all showing shorter osPFS than other disease sites. There was no difference in the osPFS of extra-thoracic sites of disease in patients with high PD-L1 expression. There was significant discordance between visceral disease response and bone disease response to ICI (p=0.047). The presence of BoMs was an independent poor prognostic factor for OS (HR 1.26, 95%CI: 1.05-1.53, p=0.01). Conclusion: Metastatic bone, liver, and intra-abdominal lesions demonstrated inferior clinical responses to ICI relative to other sites of disease. Additionally, the presence of bone and liver metastases were independent poor prognostic factors for overall survival. This real-world data suggests that BoMs respond poorly to ICI and may require treatment adjuncts for disease control.

Factor analysis of the Chinese version of the Autism Spectrum Quotient 10 and its association with schizotypal traits in adolescents and young adults in Hong Kong.

BACKGROUND: There is evidence suggesting that autistic traits are associated with schizotypal traits. This study examined the factor structure of the Autism Spectrum Quotient 10 (AQ-10) and its associations with schizotypal traits (measured by the Schizotypal Personality Questionnaire-Brief [SPQ-B]) in a cohort of Chinese adolescents and young adults. METHODS: Invitation letters, stratified by locations and housing types, were randomly sent to individuals aged 15 to 24 years for participation. Assessments were made using face-to-face or online interviews. Autistic traits were assessed using the Chinese version of the AQ-10. Schizotypal personality traits were assessed using the Chinese version of the 22-item SPQ-B. RESULTS: In total, 395 male and 536 female participants (mean age, 19.93 years) were recruited between July 2020 and May 2021. Exploratory factor analysis of the AQ-10 yielded three factors (theory of mind, task switching, and attention deficits) explaining 55.11% of the total variance. Autistic traits were positively correlated with schizotypal traits of disorganised features (r = 0.21, p < 0.001), interpersonal relationship deficits (r = 0.19, p < 0.001), and cognitive-perceptual deficits (r = 0.11, p = 0.001). CONCLUSION: In Chinese adolescents and young adults, autistic traits, especially task switching and attention deficits (compared with theory of mind) are more closely correlated with schizotypal personality traits. Disentangling the overlapping and diametrical structure of autistic traits and schizotypal traits may help understand their aetiologies, assessment, and interventions.

Beyond overlap: Considering habitat preference and fitness outcomes in the umbrella species concept.

Umbrella species and other surrogate-species approaches to conservation provide an appealing framework to extend the reach of conservation efforts beyond single species. For the umbrella species concept to be effective, populations of multiple species of concern must persist in areas protected on behalf of the umbrella species. Most assessments of the concept, however, focus exclusively on geographic overlap among umbrella and background species, and not measures that affect population persistence (e.g., habitat quality or fitness). We quantified the congruence between the habitat preferences and nesting success of a high-profile umbrella species (greater sage-grouse, Centrocercus urophasianus, hereafter "sage-grouse"), and three sympatric species of declining songbirds (Brewer's sparrow Spizella breweri, sage thasher Oreoscoptes montanus, and vesper sparrow Pooecetes gramineus) in central Wyoming, USA during 2012 - 2013. We used machine-learning methods to create data-driven predictions of sage-grouse nest-site selection and nest survival probabilities by modeling field-collected sage-grouse data relative to habitat attributes. We then used field-collected songbird data to assess whether high-quality sites for songbirds aligned with those of sage-grouse. Nest sites selected by songbirds did not coincide with sage-grouse nesting preferences, with the exception that Brewer's sparrows preferred similar nest sites to sage-grouse in 2012. Moreover, the areas that produced higher rates of songbird nest survival were unrelated to those for sage-grouse. Our findings suggest that management actions at local scales that prioritize sage-grouse nesting habitat will not necessarily enhance the reproductive success of sagebrush-associated songbirds. Measures implemented to conserve sage-grouse and other purported umbrella species at broad spatial scales likely overlap the distribution of many species, however, broad-scale overlap may not translate to fine-scale conservation benefit beyond the umbrella species itself. The maintenance of microhabitat heterogeneity important for a diversity of species of concern will be critical for a more-holistic application of the umbrella species concept.

Systematic data quality assessment of electronic health record data to evaluate study-specific fitness: Report from the PRESERVE research study.

Study-specific data quality testing is an essential part of minimizing analytic errors, particularly for studies making secondary use of clinical data. We applied a systematic and reproducible approach for study-specific data quality testing to the analysis plan for PRESERVE, a 15-site, EHR-based observational study of chronic kidney disease in children. This approach integrated widely adopted data quality concepts with healthcare-specific evaluation methods. We implemented two rounds of data quality assessment. The first produced high-level evaluation using aggregate results from a distributed query, focused on cohort identification and main analytic requirements. The second focused on extended testing of row-level data centralized for analysis. We systematized reporting and cataloguing of data quality issues, providing institutional teams with prioritized issues for resolution. We tracked improvements and documented anomalous data for consideration during analyses. The checks we developed identified 115 and 157 data quality issues in the two rounds, involving completeness, data model conformance, cross-variable concordance, consistency, and plausibility, extending traditional data quality approaches to address more complex stratification and temporal patterns. Resolution efforts focused on higher priority issues, given finite study resources. In many cases, institutional teams were able to correct data extraction errors or obtain additional data, avoiding exclusion of 2 institutions entirely and resolving 123 other gaps. Other results identified complexities in measures of kidney function, bearing on the study's outcome definition. Where limitations such as these are intrinsic to clinical data, the study team must account for them in conducting analyses. This study rigorously evaluated fitness of data for intended use. The framework is reusable and built on a strong theoretical underpinning. Significant data quality issues that would have otherwise delayed analyses or made data unusable were addressed. This study highlights the need for teams combining subject-matter and informatics expertise to address data quality when working with real world data.

Hereditary Transthyretin Amyloidosis (hATTR) with Polyneuropathy Clusters Are Located in Ancient Mining Districts: A Possible Geochemical Origin of the Disease.

Hereditary transthyretin amyloidosis (hATTR) with polyneuropathy (formerly known as Familial Amyloid Polyneuropathy (FAP)) is an endemic amyloidosis involving the harmful aggregation of proteins, most commonly transthyretin (TTR) but sometimes also apolipoprotein A-1 or gelsolin. hATTR appears to be transmitted as an autosomal dominant trait. Over 100 point mutations have been identified, with the Val30Met substitution being the most common. Yet, the mechanism of pathogenesis and the overall origin of hATTR remain unclear. Here, we argue that hATTR could be related to harmful metal exposure. hATTR incidence is unevenly distributed globally, and the three largest defined clusters exist in Japan, Portugal, and Sweden. All three disease regions are also ancient mining districts with associated metal contamination of the local environment. There are two main mechanisms for how harmful metals, after uptake into tissues and body fluids, could induce hATTR. First, the metals could directly influence the expression, function, and/or aggregation of the proteins involved in hATTR pathology. Such metal-protein interactions might constitute molecular targets for anti-hATTR drug design. Second, metal exposure could induce hATTR -associated genetic mutations, which may have happened several generations ago. These two mechanisms can occur in parallel. In conclusion, the possibility that hATTR could be related to metal exposure in geochemically defined regions deserves further attention.

Improved sensitivity in paper-based microfluidic analytical devices using a pH-responsive valve for nitrate analysis.

This paper presents an innovative application of chitosan material to be used as pH-responsive valves for the precise control of lateral flow in microfluidic paper-based analytical devices (µPADs). The fabrication of µPADs involved wax printing, while pH-responsive valves were created using a solution of chitosan in acetic acid. The valve-forming solution was applied, and ready when dry; by exposure to acidic solutions, the valve opens. Remarkably, the valves exhibited excellent compatibility with alkaline, neutral, and acidic solutions with a pH higher than 4. The valve opening process had no impact on the flow rate and colorimetric analysis. The potential of chitosan valves used for flow control was demonstrated for µPADs employed for nitrate determination. Valves were used to increase the conversion time of nitrate to nitrite, which was further analyzed using the Griess reaction. The µPAD showed a linear response in the concentration range of 10-100 µmol L-1, with a detection limit of 5.4 µmol L-1. As a proof of concept, the assay was successfully applied to detect nitrate levels in water samples from artificial lakes of recreational parks. For analyses that require controlled kinetics and involve multiple sequential steps, the use of chitosan pH-responsive valves in µPADs is extremely valuable. This breakthrough holds great potential for the development of simple and high-impact microfluidic platforms that can cater to a wide range of analytical chemistry applications.

Patterns of acute hospital and specialist palliative care use among people with non-curative upper gastrointestinal cancer.

PURPOSE: Upper gastrointestinal (GI) cancers contribute to 16.7% of UK cancer deaths. These patients make high use of acute hospital services, but detail about palliative care use is lacking. We aimed to determine the patterns of use of acute hospital and hospital specialist palliative care services in patients with advanced non-curative upper GI cancer. METHODS: We conducted a service evaluation of hospital use and palliative care for all patients with non-curative upper GI cancer seen in one large hospital, using routinely collected data (2019-2022). We report and characterise hospital admissions and palliative care within the study time period, using descriptive statistics, and multivariable Poisson regression to estimate the unadjusted and adjusted incidence rate ratio of hospital admissions. RESULTS: The total with non-curative upper GI cancer was 960. 86.7% had at least one hospital admission, with 1239 admissions in total. Patients had a higher risk of admission to hospital if: aged ≤ 65 (IRR for 66-75 years 0.71, IRR 76-85 years 0.68; IRR > 85 years 0.53; p < 0.05), or lived in an area of lower socioeconomic status (IMD Deciles 1-5) (IRR 0.90; p < 0.05). Over the 4-year period, the rate of re-admission was higher in patients not referred to palliative care (rate 0.52 readmissions/patient versus rate 1.47 readmissions/patient). CONCLUSION: People with advanced non-curative gastrointestinal cancer have frequent hospital admissions, especially if younger or from areas of lower socioeconomic status. There is clear association between specialist palliative care referral and reduced risk of hospitalisation. This evidence supports referral to specialist palliative care.

Substance use and mental health factors associated with self-reported higher risk cannabis use among people with HIV screened in primary care.

Background: While cannabis use is prevalent among people with HIV (PWH), factors associated with higher-risk use require further study. We examined factors associated with indicators risk for cannabis use disorder (CUD) among PWH who used cannabis. Methods: Participants included adult (≥18 years old) PWH from 3 HIV primary care clinics in Kaiser Permanente Northern California who reported past three-month cannabis use through the computerized Tobacco, Alcohol, Prescription medication, and other Substance use (TAPS) screening. Primary outcome was TAPS cannabis score (range 1-3), categorized as any use (1) and higher risk for CUD (≥2). Measures included sociodemographics (age, sex, race, neighborhood deprivation index [NDI]), Charlson Comorbidity Index (CCI), HIV RNA, CD4 cell counts, higher risk tobacco use (TAPS tobacco score≥2), depression, and anxiety symptoms. Unadjusted and multivariable logistic regression examined factors associated with higher risk for CUD. Results: Of the complete sample (N=978; 94.1% Male; 58.3% White; Age Mode=51-60), 35.8% reported higher risk for CUD. Unadjusted models indicated younger age, Black race, higher CCI, depression, anxiety, and higher risk tobacco use were associated with higher risk, while only Black race (OR=1.84, 95% CI[1.29, 2.63]), anxiety (OR=1.91, 95% CI[1.22, 2.98]), and higher risk tobacco use (OR=2.27, 95% CI[1.47, 3.51]) remained significant in the multivariable model. Conclusions: Black race, anxiety and tobacco use, but not HIV clinical markers, were associated with higher risk for CUD among PWH. Clinical efforts to screen and provide interventions for preventing CUD alongside anxiety and tobacco use among PWH should be evaluated.

Mucosal Melanoma of Palate: A Case Report with Review of Literature.

The World Health Organisation defines mucosal malignant melanoma as a malignant tumour of melanocytes or of melanocyte progenitors. Due to the lack of symptoms and unknown etiology, mucosal malignant melanoma may go undiagnosed. The surgeon can find it challenging to come up with a definitive treatment strategy because of its rarity and rapid spread. In this case study, a 57-year-old female patient with hyperpigmented gingiva and palate diagnosed pathologically and immunohistochemically as malignant melanoma underwent surgical excision and a modified radical neck dissection.

Acute Effects of Breaking up Sitting Time With Isometric Wall Squat Exercise on Vascular Function and Blood Pressure in Sedentary Adults: Randomized Crossover Trial.

PURPOSE: The World Health Organization has recommended breaking up sitting time to improve cardiovascular health. However, whether isometric exercise can be effectively used as a strategy to break up sitting time remains unclear. Thus, the aim of this study was to analyze the acute effects of breaking up prolonged sitting with isometric wall squat exercise (IWSE) on vascular function and blood pressure (BP) in sedentary adults. METHODS: This randomized crossover trial included 17 adults (53% male, 26 ± 6 yr, 22.4 ± 3.6 kg/m2) with high sedentary behavior (≥ 6 hr/d). The participants completed 2 experimental sessions in a randomized order, both sharing a common sitting period of 180 min: Breaks (2-min breaks were incorporated into the IWSE, with participants maintaining their knees at the angle determined by the incremental test, which occurred every 30 min) and Control (sitting for 180 min continuously). Popliteal artery flow-mediated dilation (FMD) and brachial BP were measured before and at 10 and 30 min after the experimental sessions. RESULTS: The results did not indicate significant session vs time interaction effects on popliteal FMD and brachial BP (P > .05). A subanalysis including only participants with popliteal FMD reduction after the Control session (n = 11) revealed that Breaks enhanced popliteal FMD after 10 min (1.38 ± 6.45% vs -4.87 ± 2.95%, P= .002) and 30 min (-0.43 ± 2.48% vs -2.11 ± 5.22%, P= .047). CONCLUSION: Breaking up prolonged sitting with IWSE mitigates impaired vascular function resulting from prolonged sitting but has no effect on BP in sedentary adults.

Strong diffraction effects accompany the transmission of a laser beam through inhomogeneous plasma microstructures.

In the study we thoroughly analyze diffraction effects accompanying the laser beam transmission through inhomogeneous plasma microstructures and simulate their diffraction patterns at the object output and in the near field. For this we solve the scalar Helmholtz wave equation in the first Rytov approximation and compute the diffraction spreading of the transmitted beam in free space. Diffraction effects are found to arise within the beam passage through inhomogeneous plasma microstructures even in the simplest approximations of the laser beam interaction with plasma. These effects become strong in the near-field region and significantly distort the patterns of plasma formations, as well as facilitate the appearance of various optical artifacts in the plasma images. By performing numerical simulations, we characterize in detail the features of the visualization of plasma formations in the field of a coherent laser beam registered by a lens system. The calculations are in good agreement with the experimental data. The study can find broad applications in the processing of the laser images of plasma microstructures registered by lens systems in the presence of strong diffraction effects.

Genome-wide association study for milking speed in Fleckvieh cattle.

Milking speed is an important trait influencing udder health of dairy cows as well as labor efficiency. Yet, it has received little attention in genomic association studies. The main objective of this study was to determine regions and genes on the genome with a potential effect on milking speed in Fleckvieh (dual purpose Simmental) cattle. Genome-wide association studies were conducted using de-regressed breeding values of bulls as phenotypes. Six SNP on 4 autosomes were significantly associated with milking speed for additive effects. Significant regions on BTA4 and BTA19 correspond with findings for other dairy cattle breeds. Based on the observation of Fleckvieh breed managers, variation of milking speed in batches of daughters of some bulls is much higher than in daughter groups of other bulls. This difference in within family variation may be caused by transmission of alternative alleles of bulls being heterozygous for a gene affecting milking speed. To check on this, we considered standard deviation of yield deviations in milking speed of half-sib daughters as a new trait and performed GWAS for dominance effects. One signal on BTA5 passed the genome wide Bonferroni threshold that corresponded to the significant signal from standard GWAS on de-regressed breeding values. The key conclusion of this study is that several strong genomic signals were found for milking speed in Fleckvieh cattle and that the strongest of them are supported by similar findings in Brown Swiss and Holstein Friesian cattle. Milking speed is a complex trait whose sub-processes have not yet been elucidated in detail. Hence, it remains a challenge to link the associated regions on the genome with causal genes and their functions.

Faecal microbiota transplantation for sleep disturbance in post-acute COVID-19 syndrome.

BACKGROUND & AIMS: Post-acute COVID-19 syndrome (PACS) is associated with sleep disturbance but treatment options are limited. The aetiology of PACS may be secondary to alterations in the gut microbiome. Here, we report the efficacy of faecal microbiota transplantation (FMT) in alleviating post-COVID insomnia symptoms in a non-randomised, open-label prospective interventional study. METHODS: Between September 22, 2022 and May 22, 2023, we recruited 60 PACS patients with insomnia defined as Insomnia Severity Index (ISI) ≥ 8 and assigned them to the FMT group (FMT at weeks 0, 2, 4 and 8; n=30) or the control group (n=30). The primary outcome was clinical remission defined by an ISI of less than eight at 12 weeks. Secondary outcomes included changes in the Pittsburgh Sleep Quality Index (PSQI), Generalised Anxiety Disorder-7 scale (GAD-7), Epworth Sleepiness Scale (ESS), Multidimensional Fatigue Inventory (MFI), blood cortisol and melatonin, and gut microbiome analysis on metagenomic sequencing. RESULTS: At week 12, more patients in the FMT than the control group had insomnia remission (37.9% vs 10.0%; p=0.018). The FMT group showed a decrease in ISI score (p<0.0001), PSQI (p<0.0001), GAD-7 (p=0.0019), ESS (p=0.0057) and blood cortisol concentration (p=0.035) from baseline to week 12, but there was no significant change in the control group. There was enrichment of bacteria such as Gemmiger formicilis and depletion of microbial pathways producing menaquinol derivatives after FMT. Gut microbiome profile resembled that of the donor in FMT responders but not in non-responders at week 12. There was no serious adverse event. CONCLUSION: This pilot study showed that FMT could be effective and safe in alleviating post-COVID insomnia and further clinical trials are warranted. CLINICALTRIALS: gov identifier: NCT05556733.

Molecular detection, risk factors, and phylogenetic analysis of tick-borne pathogens in dogs from northern Vietnam.

In tropical regions, numerous tick-borne pathogens (TBPs) play a crucial role as causative agents of infectious diseases in humans and animals. Recently, the population of companion and pet dogs has significantly increased in Vietnam; however, information on the occurrence of TBPs is still limited. The objectives of this investigation were to determine the occurrence rate, risk factors, and phylogenetic characteristics of TBPs in dogs from northern Vietnam. Of 341 blood samples tested by PCR, the total infection of TBPs was 73.9% (252/341). Babesia vogeli (18SrRNA gene - 30.5%) was detected most frequently in studied dogs followed by Rickettsia spp. (OmpA gene - 27%), Anaplasma platys (groEL gene - 22%), Bartonella spp. (16SrRNA - 18.8%), Mycoplasma haemocanis (16SrRNA - 9.4%) and Hepatozoon canis (18SrRNA gene - 1.2%), respectively. All samples were negative for Ehrlichia canis and Anaplasma phagocytophylum. Co-infection was detected in 31.4% of the samples (107/341) of which, A. platys/Bartonella spp. (34/94,10%), Rickettsia spp./B. vogeli (19/94, 5.6%), and M. haemocanis/B. vogeli (19/94, 5.6%) were recorded as the three most frequent two species of co-infection types. Statistical analysis revealed a significant correlation between TBP infection and several host variables regarding age, breed, and living area in the current study. The recent findings reported herein, for the first time in Vietnam, are essential for local veterinarians when considering the appropriate approaches for diagnosing these diseases. Furthermore, this data can be used to establish control measures for future surveillance and prevention strategies against canine TBPs in Vietnam.

Progenitor-like cells contributing to cellular heterogeneity in the nucleus pulposus are lost in intervertebral disc degeneration.

The nucleus pulposus (NP) in the intervertebral disc (IVD) arises from embryonic notochord. Loss of notochordal-like cells in humans correlates with onset of IVD degeneration, suggesting that they are critical for healthy NP homeostasis and function. Comparative transcriptomic analyses identified expression of progenitor-associated genes (GREM1, KRT18, and TAGLN) in the young mouse and non-degenerated human NP, with TAGLN expression reducing with aging. Lineage tracing using Tagln-CreERt2 mice identified peripherally located proliferative NP (PeriNP) cells in developing and postnatal NP that provide a continuous supply of cells to the entire NP. PeriNP cells were diminished in aged mice and absent in puncture-induced degenerated discs. Single-cell transcriptomes of postnatal Tagln-CreERt2 IVD cells indicate enrichment for TGF-ß signaling in Tagln descendant NP sub-populations. Notochord-specific removal of TGF-ß/BMP mediator Smad4 results in loss of Tagln+ cells and abnormal NP morphologies. We propose Tagln+ PeriNP cells are potential progenitors crucial for NP homeostasis.

Tinnitus update: what can be done for the ringing?

Physicians will frequently encounter patients who report tinnitus. Tinnitus is a symptom whereby there is the perception of sound or sounds in the ear or head in the absence of an external source of sound. Most individuals experiencing tinnitus will have a neutral reaction to the percept, but in a small proportion of patients, tinnitus can be a debilitating symptom. When it causes burden, patients can be affected in multiple different facets of life, including impairment in sleep, hearing cognition and psychological and psychiatric well-being, often resulting in high healthcare utilisation and societal costs. Hence, chronic, disabling tinnitus is a complex condition with multifactorial causes and multiple perpetuating biopsychosocial factors. Despite efforts to increase knowledge about its pathophysiology and research into treatments, little impact on real-world clinical practice has been seen. There are no proven effective pharmacological treatments or complementary medicines specifically for chronic, disabling tinnitus. Despite this, there is a role for treating this condition through a multidisciplinary approach specifically targeting comorbid active psychiatric conditions, using hearing aids in appropriate clinical settings such as in those with a coassociated confirmed hearing loss, and specialised cognitive behavioural therapy for patients reporting bothersome tinnitus. Cognitive behavioural therapy remains the most valuable evidence-based intervention in this regard. This narrative review attempts to summarise the current understanding in terms of pathophysiology, assessment and treatment of tinnitus for the internal physician who may encounter patients with disabling, chronic tinnitus.

Association of Admission Glycemic Gap on Short-term Outcome of Neuro-critical Patients with Diabetes.

Both of neurological emergencies and hyperglycemia are independently associated risk factors of mortality in the ICU patients. In critically ills, hyperglycemia is secondary to already existing DM or stress-induced hyperglycemia (SIH). Admission glycemic gap (AGG) is considered as a reliable indicator of SIH. This study aimed to explore the association of AGG on diabetic neuro-critical patients' short-term mortality, and understand the potential of AGG as the predictor of outcome. Sixty adult diabetic neuro-critical patients admitted in ICU and stayed at least for 24 hours, were prospectively observed for 30 days, or until discharge or death, whichever came first. The patients' initial clinical assessment and HbA1c, CBC, ABG, and blood glucose level were done within 24 hours of admission. A1c derived admission glucose (ADAG) was calculated as, ADAG = (1.59 × HbA1c) - 2.59 (mmol/L). The AGG was calculated by subtracting ADAG from admission blood glucose level (ABGL). Death or survival of 30 days was our primary outcome and participants were divided between survivor or non-survivor groups according to primary outcome. Statistical comparisons of the study variables between the groups were performed and the relationship between parameters derived from blood glucose and mortality was prospected. Among the 60 patients enrolled, 35(58.3%) were non-survivors and 25(41.7%) were survivors. Age, sex, residence, primary diagnosis, co-morbidity, or drug history had no association with survival/non-survival. Among the initial clinical assessment parameters, lower GCS had significant association with non-survival. AGG, HbA1c, ADAG and ABGL were significantly different between the groups, with higher values in the non-survivors. Lower GCS, and higher AGG, HbA1c, ADAG and ABGL showed significant odds of non-survival. The highest odds of non- survival was for AGG (OR 2.95, 95% CI: 1.83-4.75; p<0.001). For ABGL and HbA1c the OR were 2.03 (95% CI: 1.44-2.86; p<0.001) and 1.93 (95% CI: 1.04-3.58; p<0.04) respectively. The final adjusted odds (aOR) of non-survival for higher AGG was 3.25 (95% CI: 1.71-6.16; p<0.001), signifying that AGG is independently associated with non-survival. AGG, GCS level, ABGL, HbA1c level, and ADAG can predict short-term outcome (mortality). However, AGG has the greatest potential to predict short-term outcome in diabetic neuro-critical patients.

Application of Cyclic Diaryliodonium Salts in the Synthesis of Axially Chiral Natural Product Analogues.

The application of cyclic diaryliodonium salts in the synthesis of bioactive natural product analogues was demonstrated. Axially chiral biaryls were obtained via the enantioselective ring opening of cyclic diaryliodonium salts. Regioselective borylation was key in accessing both enantiomers of a biphenol key intermediate in eight steps overall. 8,8″-Amino biflavones were synthesized, their bioactivity profiled, and the eutomer identified. The structure-activity relationship was probed.