Surviving IRS Examinations and Appeals

This article summarizes the statutory, regulatory and administrative rules and procedures that apply to IRS civil tax examinations and Appeals proceedings, including alternative dispute resolution procedures. The focus of this paper is on field examinations, rather than service center examinations, correspondence examinations, or office examinations. In addition, it attempts to answer some of the basic questions that taxpayers often ask their advisors and representatives when they are the subject of an IRS civil tax examination: Why was I selected by the IRS for audit? How long will this audit take? Why do the agents want all this information, documents, data, etc.? Do I have to give the agents all the information, documents, data, etc. they have requested? What can the IRS do if I don\u27t cooperate in the audit? Can I recover from the IRS the fees and expenses I incur in the audit an din the Appeals proceeding? Should I ask for an Appeals conference

Climate-driven regime shifts in a mangrove-salt marsh ecotone over the past 250 years.

Climate change is driving the tropicalization of temperate ecosystems by shifting the range edges of numerous species poleward. Over the past few decades, mangroves have rapidly displaced salt marshes near multiple poleward mangrove range limits, including in northeast Florida. It is uncertain whether such mangrove expansions are due to anthropogenic climate change or natural climate variability. We combined historical accounts from books, personal journals, scientific articles, logbooks, photographs, and maps with climate data to show that the current ecotone between mangroves and salt marshes in northeast Florida has shifted between mangrove and salt marsh dominance at least 6 times between the late 1700s and 2017 due to decadal-scale fluctuations in the frequency and intensity of extreme cold events. Model projections of daily minimum temperature from 2000 through 2100 indicate an increase in annual minimum temperature by 0.5 °C/decade. Thus, although recent mangrove range expansion should indeed be placed into a broader historical context of an oscillating system, climate projections suggest that the recent trend may represent a more permanent regime shift due to the effects of climate change

SARS‑CoV‑2 entry into and evolution within a skilled nursing facility

SARS-CoV-2 belongs to the family Coronaviridae which includes multiple human pathogens that have an outsized impact on aging populations. As a novel human pathogen, SARS-CoV-2 is undergoing continuous adaptation to this new host species and there is evidence of this throughout the scientific and public literature. However, most investigations of SARS-CoV-2 evolution have focused on largescale collections of data across diverse populations and/or living environments. Here we investigate SARS-CoV-2 evolution in epidemiologically linked individuals within a single outbreak at a skilled nursing facility beginning with initial introduction of the pathogen. The data demonstrate that SARSCoV- 2 was introduced to the facility multiple times without establishing an interfacility transmission chain, followed by a single introduction that infected many individuals within a week. This largescale introduction by a single genotype then persisted in the facility. SARS-CoV-2 sequences were investigated at both the consensus and intra-host variation levels. Understanding the variability in SARS-CoV-2 during transmission chains will assist in understanding the spread of this disease and can ultimately inform best practices for mitigation strategies

The Relationship of Area-Level Sociodemographic Characteristics, Household Composition and Individual-Level Socioeconomic Status on Walking Behavior Among Adults

Understanding the contextual factors associated with why adults walk is important for those interested in increasing walking as a mode of transportation and leisure. This paper investigates the relationships between neighborhood-level sociodemographic context, individual level sociodemographic characteristics and walking for leisure and transport. Data from two community-based studies of adults (n = 550) were used to determine the association between the Area Sociodemographic Environment (ASDE), calculated from U.S. Census variables, and individual-level SES as potential correlates of walking behavior. Descriptive statistics, mean comparisons and Pearson’s correlations coefficients were used to assess bivariate relationships. Generalized estimating equations were used to model the relationship between ASDE, as quartiles, and walking behavior. Adjusted models suggest adults engage in more minutes of walking for transportation and less walking for leisure in the most disadvantaged compared to the least disadvantaged neighborhoods but adding individual level demographics and SES eliminated the significant results. However, when models were stratified for free or reduced cost lunch, of those with children who qualified for free or reduced lunch, those who lived in the wealthiest neighborhoods engaged in 10.7 min less of total walking per day compared to those living in the most challenged neighborhoods (p < 0.001). Strategies to increase walking for transportation or leisure need to take account of individual level socioeconomic factors in addition to area-level measures

Improving Biosecurity through Instructional Crisis Communication: Lessons Learned from the PEDv Outbreak

Crises, by their nature, demand effectively designed and quickly delivered instructional messages that compel stakeholders to take appropriate actions to protect themselves and their assets. The challenges of crisis communication are intensified in crises involving unanticipated and relatively unknown disease outbreaks with the potential to spread exponentially. This study assesses the communication challenges and opportunities in such volatile crises through an analysis of the Porcine Epidemic Diarrhea virus (PEDv) outbreak that severely threatened the United States pork industry in 2013 and 2014. Interviews were conducted with 13 individuals directly involved in developing and distributing risk and crisis biosecurity messages during the PEDv outbreak. Participants were selected based on affiliation with the National Pork Board, American Association of Swine Veterinarians, university extension, or their swine industry expertise. Four generalizable implications emerged: 1) the advantage of maintaining flexibility in crisis communication planning; 2) the value of audience analysis and message adaptation; 3) the importance of understanding not only what to do, but also why the recommended actions are essential; and 4) the utility of risk/crisis communication and education both prior to and during a crisis event

Identification of folate receptor α (FRα) binding oligopeptides and their evaluation for targeted virotherapy applications

Oncolytic virotherapies (OV) based on human adenoviral (HAdV) vectors hold significant promise for the treatment of advanced ovarian cancers where local, intraperitoneal delivery to tumour metastases is feasible, bypassing many complexities associated with intravascular delivery. The efficacy of HAdV-C5-based OV is hampered by a lack of tumour selectivity, where the primary receptor, hCAR, is commonly downregulated during malignant transformation. Conversely, folate receptor alpha (FRα) is highly expressed on ovarian cancer cells, providing a compelling target for tumour selective delivery of virotherapies. Here, we identify high-affinity FRα-binding oligopeptides for genetic incorporation into HAdV-C5 vectors. Biopanning identified a 12-mer linear peptide, DWSSWVYRDPQT, and two 7-mer cysteine-constrained peptides, CIGNSNTLC and CTVRTSAEC that bound FRα in the context of the phage particle. Synthesised lead peptide, CTVRTSAEC, bound specifically to FRα and could be competitively inhibited with folic acid. To assess the capacity of the elucidated FRα-binding oligopeptides to target OV to FRα, we genetically incorporated the peptides into the HAdV-C5 fiber-knob HI loop including in vectors genetically ablated for hCAR interactions. Unfortunately, the recombinant vectors failed to efficiently target transduction via FRα due to defective intracellular trafficking following entry via FRα, indicating that whilst the peptides identified may have potential for applications for targeted drug delivery, they require additional refinement for targeted virotherapy applications

Role of the mesoamygdaloid dopamine projection in emotional learning

Amygdala dopamine is crucially involved in the acquisition of Pavlovian associations, as measured via conditioned approach to the location of the unconditioned stimulus (US). However, learning begins before skeletomotor output, so this study assessed whether amygdala dopamine is also involved in earlier 'emotional' learning. A variant of the conditioned reinforcement (CR) procedure was validated where training was restricted to curtail the development of selective conditioned approach to the US location, and effects of amygdala dopamine manipulations before training or later CR testing assessed. Experiment 1a presented a light paired (CS+ group) or unpaired (CS- group) with a US. There were 1, 2 or 10 sessions, 4 trials per session. Then, the US was removed, and two novel levers presented. One lever (CR+) presented the light, and lever pressing was recorded. Experiment 1b also included a tone stimulus. Experiment 2 applied intra-amygdala R(+) 7-OH-DPAT (10 nmol/1.0 A mu l/side) before two training sessions (Experiment 2a) or a CR session (Experiment 2b). For Experiments 1a and 1b, the CS+ group preferred the CR+ lever across all sessions. Conditioned alcove approach during 1 or 2 training sessions or associated CR tests was low and nonspecific. In Experiment 2a, R(+) 7-OH-DPAT before training greatly diminished lever pressing during a subsequent CR test, preferentially on the CR+ lever. For Experiment 2b, R(+) 7-OH-DPAT infusions before the CR test also reduced lever pressing. Manipulations of amygdala dopamine impact the earliest stage of learning in which emotional reactions may be most prevalent

Inventing the Neolithic? Putting evidence-based interpretation back into the study of faunal remains from causewayed enclosures.

ArticleThis is an Accepted Manuscript of an article published by Taylor & Francis in World Archaeology on 2015, available online: http://wwww.tandfonline.com/10.1080/00438243.2015.1072476The paper argues that our current understanding of the animal bones from causewayed enclosure sites in Britain is flawed. During the 1980-90s, a number of key interpretations, still frequently espoused, were based more upon anecdote and theory-driven assertion than on empirical evidence. An example is that evidence of bone processing (butchery and bone fracture) does not feature heavily in the faunal record from causewayed enclosures. Using data from the sites of Etton and Staines, this view must now be questioned. Both butchery and peri-mortem bone fracture are present in these assemblages in substantial quantities. These sites are compared with Ludwinowo 7, a Linearbandkeramik settlement site in Poland and there are considerable similarities between the three different sites. This suggests possibility that the broader economic utility of animal bone assemblages at causewayed enclosures has been underestimated, having been, up to now, regarded as ‘not indicative of domestic settlement’

Ethnic differences in the indirect effects of the COVID-19 pandemic on clinical monitoring and hospitalisations for non-COVID conditions in England: a population-based, observational cohort study using the OpenSAFELY platform

Background: The COVID-19 pandemic disrupted healthcare and may have impacted ethnic inequalities in healthcare. We aimed to describe the impact of pandemic-related disruption on ethnic differences in clinical monitoring and hospital admissions for non-COVID conditions in England. // Methods: In this population-based, observational cohort study we used primary care electronic health record data with linkage to hospital episode statistics data and mortality data within OpenSAFELY, a data analytics platform created, with approval of NHS England, to address urgent COVID-19 research questions. We included adults aged 18 years and over registered with a TPP practice between March 1, 2018, and April 30, 2022. We excluded those with missing age, sex, geographic region, or Index of Multiple Deprivation. We grouped ethnicity (exposure), into five categories: White, Asian, Black, Other, and Mixed. We used interrupted time-series regression to estimate ethnic differences in clinical monitoring frequency (blood pressure and Hba1c measurements, chronic obstructive pulmonary disease and asthma annual reviews) before and after March 23, 2020. We used multivariable Cox regression to quantify ethnic differences in hospitalisations related to diabetes, cardiovascular disease, respiratory disease, and mental health before and after March 23, 2020. // Findings: Of 33,510,937 registered with a GP as of 1st January 2020, 19,064,019 were adults, alive and registered for at least 3 months, 3,010,751 met the exclusion criteria and 1,122,912 were missing ethnicity. This resulted in 14,930,356 adults with known ethnicity (92% of sample): 86.6% were White, 7.3% Asian, 2.6% Black, 1.4% Mixed ethnicity, and 2.2% Other ethnicities. Clinical monitoring did not return to pre-pandemic levels for any ethnic group. Ethnic differences were apparent pre-pandemic, except for diabetes monitoring, and remained unchanged, except for blood pressure monitoring in those with mental health conditions where differences narrowed during the pandemic. For those of Black ethnicity, there were seven additional admissions for diabetic ketoacidosis per month during the pandemic, and relative ethnic differences narrowed during the pandemic compared to the White ethnic group (Pre-pandemic hazard ratio (HR): 0.50, 95% confidence interval (CI) 0.41, 0.60, Pandemic HR: 0.75, 95% CI: 0.65, 0.87). There was increased admissions for heart failure during the pandemic for all ethnic groups, though highest in those of White ethnicity (heart failure risk difference: 5.4). Relatively, ethnic differences narrowed for heart failure admission in those of Asian (Pre-pandemic HR 1.56, 95% CI 1.49, 1.64, Pandemic HR 1.24, 95% CI 1.19, 1.29) and Black ethnicity (Pre-pandemic HR 1.41, 95% CI: 1.30, 1.53, Pandemic HR: 1.16, 95% CI 1.09, 1.25) compared with White ethnicity. For other outcomes the pandemic had minimal impact on ethnic differences. // Interpretation: Our study suggests that ethnic differences in clinical monitoring and hospitalisations remained largely unchanged during the pandemic for most conditions. Key exceptions were hospitalisations for diabetic ketoacidosis and heart failure, which warrant further investigation to understand the causes

PPIP5K2 and PCSK1 are Candidate Genetic Contributors to Familial Keratoconus

Keratoconus (KC) is the most common corneal ectatic disorder affecting &gt;300,000 people in the US. KC normally has its onset in adolescence, progressively worsening through the third to fourth decades of life. KC patients report significant impaired vision-related quality of life. Genetic factors play an important role in KC pathogenesis. To identify novel genes in familial KC patients, we performed whole exome and genome sequencing in a four-generation family. We identified potential variants in the PPIP5K2 and PCSK1 genes. Using in vitro cellular model and in vivo gene-trap mouse model, we found critical evidence to support the role of PPIP5K2 in normal corneal function and KC pathogenesis. The gene-trap mouse showed irregular corneal surfaces and pathological corneal thinning resembling KC. For the first time, we have integrated corneal tomography and pachymetry mapping into characterization of mouse corneal phenotypes which could be widely implemented in basic and translational research for KC diagnosis and therapy in the future