Long-Term Capital Gains Tax Strategies: Correlated Protective Put Strategy

A reduction in the long-term capital gains tax rate provides investors with new strategies to minimize taxes and protect investment gains.  One such opportunity exists when an investor decides to sell a profitable stock with a holding period of less than one-year, resulting in short-term ordinary taxes.  The investor would find it more beneficial to sell the stock after one-year lapses, resulting in lower long-term capital gain taxes, although the longer holding period exposes the investor to the uncertainty of stock price movement.  A strategy to extend the holding period without excess risk would be to use the protective put option strategy, sometimes referred to as “investment insurance”.  The strategy involves the purchase of a put option to protect against the possible decline in the stock price, to take advantage of the lower long-term capital gains tax rate, and to preserve the upside potential of the stock.  Pursuant to IRS Publication 550, the IRS does not allow the use of a protective put to extend the holding period on the same security considered for sale.  Since the IRS does not allow a direct protective put hedge, this study will explore an alternative strategy involving the purchase of a put on a highly correlated investment to extend the holding period to recognize lower capital gains tax rates.  The paper presents example situations when an investor benefits from utilizing the correlated protective put option strategy

Synthesis of oxindoles and benozfuranones via oxidation of 2-heterocyclic BMIDAs

The synthesis of functionalized oxindoles and benzofuranones via oxidation of 2-BMIDA indoles and benzofurans, respectively, is described. Interconversion of boron species (BMIDAàBF3K) was necessary to enable oxidation and overcome boronic acid stability issues associated with a difficult BMIDA hydrolysis. Overall, a robust process was developed that allowed access to a small library of oxindole and benzofuranone products and facilitated the step-efficient synthesis of biologically-active compounds containing the oxindole pharmacophore

Replication and exploratory analysis of 24 candidate risk polymorphisms for neural tube defects.

BackgroundNeural tube defects (NTDs), which are among the most common congenital malformations, are influenced by environmental and genetic factors. Low maternal folate is the strongest known contributing factor, making variants in genes in the folate metabolic pathway attractive candidates for NTD risk. Multiple studies have identified nominally significant allelic associations with NTDs. We tested whether associations detected in a large Irish cohort could be replicated in an independent population.MethodsReplication tests of 24 nominally significant NTD associations were performed in racially/ethnically matched populations. Family-based tests of fifteen nominally significant single nucleotide polymorphisms (SNPs) were repeated in a cohort of NTD trios (530 cases and their parents) from the United Kingdom, and case-control tests of nine nominally significant SNPs were repeated in a cohort (190 cases, 941 controls) from New York State (NYS). Secondary hypotheses involved evaluating the latter set of nine SNPs for NTD association using alternate case-control models and NTD groupings in white, African American and Hispanic cohorts from NYS.ResultsOf the 24 SNPs tested for replication, ADA rs452159 and MTR rs10925260 were significantly associated with isolated NTDs. Of the secondary tests performed, ARID1A rs11247593 was associated with NTDs in whites, and ALDH1A2 rs7169289 was associated with isolated NTDs in African Americans.ConclusionsWe report a number of associations between SNP genotypes and neural tube defects. These associations were nominally significant before correction for multiple hypothesis testing. These corrections are highly conservative for association studies of untested hypotheses, and may be too conservative for replication studies. We therefore believe the true effect of these four nominally significant SNPs on NTD risk will be more definitively determined by further study in other populations, and eventual meta-analysis

Outcome measures for use in trials of paediatric otorrhoea:A systematic review

Introduction:Paediatric otorrhoea (PO) describes a middle ear infection that results in a perforation of the tympanic membrane and ear discharge, in children and young people (CYP). Prolonged infection may be associated with hearing loss and developmental delay. The current management of paediatric otorrhoea is variable, including non-invasive treatments (conservative, oral antibiotics, topical antibiotics) and surgery, reflecting the lack of a sufficiently strong evidence base. Outcome reporting is fundamental to producing reliable and meaningful evidence to inform best practice.Objectives:Primary objective: to determine which outcome measures are currently used to evaluate treatment success in studies of non-surgical treatments for paediatric otorrhoea. Secondary objectives: to identify outcome measurement instruments used in the literature and assess their applicability for use in clinical trials of PO.Methods:This systematic review was registered with PROSPERO (CRD42023407976). Database searches of EMBASE, MEDLINE and Cochrane was performed on June 6, 2023, covering from Jan 1995 to May 2023. Randomised controlled trials or study protocols involving CYP with PO were included following PRISMA guidelines. Risk of bias was assessed with Cochrane's tool.Results:Of the 377 papers identified, six were included in the systematic review. The primary outcome of five of the studies related to otorrhoea cessation; both time to cessation and proportion recovered at various time points were used as measures. Two measurement instruments were identified: Otitis Media-6 Questionnaire and the Institute for Medical Technology Assessment Productivity Cost Questionnaire. Both were shown to be applicable measurement instruments when used in clinical trials of PO.Conclusions:To promote homogeneity and facilitate meaningful comparison and combination of studies, we propose that time to cessation of otorrhoea from onset of otorrhoea should be used as the primary outcome in future studies. Further research is needed to establish if this is the most important outcome to children and their caregivers

Analysis of lesion localisation at colonoscopy: outcomes from a multi-centre U.K. study

Background: Colonoscopy is currently the gold standard for detection of colorectal lesions, but may be limited in anatomically localising lesions. This audit aimed to determine the accuracy of colonoscopy lesion localisation, any subsequent changes in surgical management and any potentially influencing factors. Methods: Patients undergoing colonoscopy prior to elective curative surgery for colorectal lesion/s were included from 8 registered U.K. sites (2012–2014). Three sets of data were recorded: patient factors (age, sex, BMI, screener vs. symptomatic, previous abdominal surgery); colonoscopy factors (caecal intubation, scope guide used, colonoscopist accreditation) and imaging modality. Lesion localisation was standardised with intra-operative location taken as the gold standard. Changes to surgical management were recorded. Results: 364 cases were included; majority of lesions were colonic, solitary, malignant and in symptomatic referrals. 82% patients had their lesion/s correctly located at colonoscopy. Pre-operative CT visualised lesion/s in only 73% of cases with a reduction in screening patients (64 vs. 77%; p = 0.008). 5.2% incorrectly located cases at colonoscopy underwent altered surgical management, including conversion to open. Univariate analysis found colonoscopy accreditation, scope guide use, incomplete colonoscopy and previous abdominal surgery significantly influenced lesion localisation. On multi-variate analysis, caecal intubation and scope guide use remained significant (HR 0.35, 0.20–0.60 95% CI and 0.47; 0.25–0.88, respectively). Conclusion: Lesion localisation at colonoscopy is incorrect in 18% of cases leading to potentially significant surgical management alterations. As part of accreditation, colonoscopists need lesion localisation training and awareness of when inaccuracies can occur

Microfluidics as a Novel Technique for Tuberculosis: From Diagnostics to Drug Discovery

Tuberculosis (TB) remains a global healthcare crisis, with an estimated 5.8 million new cases and 1.5 million deaths in 2020. TB is caused by infection with the major human pathogen Mycobacterium tuberculosis, which is difficult to rapidly diagnose and treat. There is an urgent need for new methods of diagnosis, sufficient in vitro models that capably mimic all physiological conditions of the infection, and high-throughput drug screening platforms. Microfluidic-based techniques provide single-cell analysis which reduces experimental time and the cost of reagents, and have been extremely useful for gaining insight into monitoring microorganisms. This review outlines the field of microfluidics and discusses the use of this novel technique so far in M. tuberculosis diagnostics, research methods, and drug discovery platforms. The practices of microfluidics have promising future applications for diagnosing and treating TB

Dynamic Blood-Brain Barrier Regulation in Mild Traumatic Brain Injury

Whereas the diagnosis of moderate and severe traumatic brain injury (TBI) is readily visible on current medical imaging paradigms (magnetic resonance imaging [MRI] and computed tomography [CT] scanning), a far greater challenge is associated with the diagnosis and subsequent management of mild TBI (mTBI), especially concussion which, by definition, is characterized by a normal CT. To investigate whether the integrity of the blood-brain barrier (BBB) is altered in a high-risk population for concussions, we studied professional mixed martial arts (MMA) fighters and adolescent rugby players. Additionally, we performed the linear regression between the BBB disruption defined by increased gadolinium contrast extravasation on dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) on MRI and multiple biomechanical parameters indicating the severity of impacts recorded using instrumented mouthguards in professional MMA fighters. MMA fighters were examined pre-fight for a baseline and again within 120 h post-competitive fight, whereas rugby players were examined pre-season and again post-season or post-match in a subset of cases. DCE-MRI, serological analysis of BBB biomarkers, and an analysis of instrumented mouthguard data, was performed. Here, we provide pilot data that demonstrate disruption of the BBB in both professional MMA fighters and rugby players, dependent on the level of exposure. Our data suggest that biomechanical forces in professional MMA and adolescent rugby can lead to BBB disruption. These changes on imaging may serve as a biomarker of exposure of the brain to repetitive subconcussive forces and mTBI

Palaeoproteomics resolves sloth relationships

The living tree sloths Choloepus and Bradypus are the only remaining members of Folivora, a major xenarthran radiation that occupied a wide range of habitats in many parts of the western hemisphere during the Cenozoic, including both continents and the West Indies. Ancient DNA evidence has played only a minor role in folivoran systematics, as most sloths lived in places not conducive to genomic preservation. Here we utilize collagen sequence information, both separately and in combination with published mitochondrial DNA evidence, to assess the relationships of tree sloths and their extinct relatives. Results from phylogenetic analysis of these datasets differ substantially from morphology-based concepts: Choloepus groups with Mylodontidae, not Megalonychidae; Bradypus and Megalonyx pair together as megatherioids, while monophyletic Antillean sloths may be sister to all other folivorans. Divergence estimates are consistent with fossil evidence for mid-Cenozoic presence of sloths in the West Indies and an early Miocene radiation in South America

Bioinformatic and Genetic Association Analysis of MicroRNA Target Sites in One-Carbon Metabolism Genes

One-carbon metabolism (OCM) is linked to DNA synthesis and methylation, amino acid metabolism and cell proliferation. OCM dysfunction has been associated with increased risk for various diseases, including cancer and neural tube defects. MicroRNAs (miRNAs) are ∼22 nt RNA regulators that have been implicated in a wide array of basic cellular processes, such as differentiation and metabolism. Accordingly, mis-regulation of miRNA expression and/or activity can underlie complex disease etiology. We examined the possibility of OCM regulation by miRNAs. Using computational miRNA target prediction methods and Monte-Carlo based statistical analyses, we identified two candidate miRNA “master regulators” (miR-22 and miR-125) and one candidate pair of “master co-regulators” (miR-344-5p/484 and miR-488) that may influence the expression of a significant number of genes involved in OCM. Interestingly, miR-22 and miR-125 are significantly up-regulated in cells grown under low-folate conditions. In a complementary analysis, we identified 15 single nucleotide polymorphisms (SNPs) that are located within predicted miRNA target sites in OCM genes. We genotyped these 15 SNPs in a population of healthy individuals (age 18–28, n = 2,506) that was previously phenotyped for various serum metabolites related to OCM. Prior to correction for multiple testing, we detected significant associations between TCblR rs9426 and methylmalonic acid (p  =  0.045), total homocysteine levels (tHcy) (p  =  0.033), serum B12 (p < 0.0001), holo transcobalamin (p < 0.0001) and total transcobalamin (p < 0.0001); and between MTHFR rs1537514 and red blood cell folate (p < 0.0001). However, upon further genetic analysis, we determined that in each case, a linked missense SNP is the more likely causative variant. Nonetheless, our Monte-Carlo based in silico simulations suggest that miRNAs could play an important role in the regulation of OCM

Recent Region-wide Declines in Caribbean Reef Fish Abundance

Profound ecological changes are occurring on coral reefs throughout the tropics, with marked coral cover losses and concomitant algal increases, particularly in the Caribbean region. Historical declines in the abundance of large Caribbean reef fishes likely reflect centuries of overexploitation. However, effects of drastic recent degradation of reef habitats on reef fish assemblages have yet to be established. By using meta-analysis, we analyzed time series of reef fish density obtained from 48 studies that include 318 reefs across the Caribbean and span the time period 1955–2007. Our analyses show that overall reef fish density has been declining significantly for more than a decade, at rates that are consistent across all subregions of the Caribbean basin (2.7% to 6.0% loss per year) and in three of six trophic groups. Changes in fish density over the past half-century are modest relative to concurrent changes in benthic cover on Caribbean reefs. However, the recent significant decline in overall fish abundance and its consistency across several trophic groups and among both fished and nonfished species indicate that Caribbean fishes have begun to respond negatively to habitat degradation