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Coronavirus Disease 2019 (COVID-19), caused by Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2), has created a global pandemic infecting over 230 million people and costing millions of lives. Therapies to attenuate severe disease are desperately needed. Cenicriviroc (CVC), a C-C chemokine receptor type 5 (CCR5) and C-C chemokine receptor type 2 (CCR2) antagonist, an agent previously studied in advanced clinical trials for patients with HIV or nonalcoholic steatohepatitis (NASH), may have the potential to reduce respiratory and cardiovascular organ failures related to COVID-19. Inhibiting the CCR2 and CCR5 pathways could attenuate or prevent inflammation or fibrosis in both early and late stages of the disease and improve outcomes of COVID-19. Clinical trials using CVC either in addition to standard of care (SoC; e.g., dexamethasone) or in combination with other investigational agents in patients with COVID-19 are currently ongoing. These trials intend to leverage the anti-inflammatory actions of CVC for ameliorating the clinical course of COVID-19 and prevent complications. This article reviews the literature surrounding the CCR2 and CCR5 pathways, their proposed role in COVID-19, and the potential role of CVC to improve outcomes.

Background Limited understanding of the diversity of variants in the cystic fibrosis transmembrane conductance regulator ( CFTR ) gene across ancestries hampers efforts to advance molecular diagnosis of cystic fibrosis (CF). The consequences pose a risk of delayed diagnoses and subsequently worsened health outcomes for patients. Therefore, characterizing the spectrum of CFTR variants across ancestries is critical for revolutionizing molecular diagnoses of CF. Methods We analyzed 454,727 UK Biobank (UKBB) whole-exome sequences to characterize the diversity of CFTR variants across ancestries. Using the PanUKBB classification, the participants were assigned into six major groups: African (AFR), American/American Admixed (AMR), Central South Asia (CSA), East Asian (EAS), European (EUR), and Middle East (MID). We segregated ancestry-specific CFTR variants, including those that are CF-causing or clinically relevant. The ages of certain CF-causing variants were determined and analyzed for selective pressure effects, and curated phenotype analysis was performed for participants with clinically relevant CFTR genotypes. Results We detected over 4000 CFTR variants, including novel ancestry-specific variants, across six ancestries. Europeans had the most unique CFTR variants [ n  = 2212], while the American group had the least unique variants [ n  = 23]. F508del was the most prevalent CF-causing variant found in all ancestries, except in EAS, where V520F was the most prevalent. Common EAS variants such as 3600G > A, V456A, and V520, which appeared approximately 270, 215, and 338 generations ago, respectively, did not show evidence of selective pressure. Sixteen participants had two CF-causing variants, with two being diagnosed with CF. We found 154 participants harboring a CF-causing and varying clinical consequences (VCC) variant. Phenotype analysis performed for participants with multiple clinically relevant variants returned significant associations with CF and its pulmonary phenotypes [Bonferroni-adjusted p  < 0.05]. Conclusions We leveraged the UKBB database to comprehensively characterize the broad spectrum of CFTR variants across ancestries. The detection of over 4000 CFTR variants, including several ancestry-specific and uncharacterized CFTR variants, warrants the need for further characterization of their functional and clinical relevance. Overall, the presentation of classical CF phenotypes seen in non-CF diagnosed participants with more than one CF-causing variant indicates that they may benefit from current CFTR modulator therapies.

Gemäß EU-Aufnahmerichtlinie 2013/33/EU ist Deutschland zur rechtlichen Verankerung geeigneter Maßnahmen bei der Unterbringung Geflüchteter sowie zur Identifizierung besonderer Schutzbedarfe verpflichtet. Lesbische, schwule, bisexuelle, trans- und intergeschlechtliche (LSBTI*) Geflüchtete werden in der Richtlinie nicht als besonders schutzbedürftige Gruppen benannt. Zwar hat die Bundesregierung 2017 bei der Ergänzung der bundesweiten Mindeststandards zum Schutz von geflüchteten Menschen in Flüchtlingsunterkünften dem LSBTI*-Schutzbedarf durch einen Katalog spezifischer Schutzmaßnahmen Rechnung getragen, jedoch liegt die Kompetenz bezüglich der Unterbringung und des Gewaltschutzes bei den Bundesländern. Der Artikel analysiert daher die vorliegenden Gewaltschutzkonzepte der Bundesländer im Hinblick auf die Verankerung dieses besonderen Schutzbedarfs. LSBTI*-relevante Schutzmaßnahmen werden in Form von Clustern detailliert vorgestellt und so spezifische Bedarfe herausgearbeitet. Insgesamt verfügten im Beobachtungszeitraum (01.01.-10.03.2019) nur 9 von 16 Bundesländern über ein Gewaltschutzkonzept – diese verankerten im Schnitt weniger als ein Drittel der in den Mindeststandards beschriebenen LSBTI*-spezifischen Schutzmaßnahmen. Schlagwörter: LSBTI*-Geflüchtete; Gewaltschutz; Homo- und Transfeindlichkeit; Asyl; Geschlechtsspezifische Diskriminierung / “If specific needs are identified” – Analysing federal states’ legal provisions for the protection of LGBTI refugees in Germany. Abstract: As specified in the European Directive 2013/33/EU, Germany is legally obligated to implement appropriate measures in refugee accommodation and to identify particularly vulnerable persons and their needs. The directive does not include lesbian, gay, bisexual, transgender and intersex (LGBTI+) refugees in the group of particularly vulnerable persons. Although Germany’s federal government does recognise their specific vulnerability in ist 2017 edition of the federal Minimum Standards for the Protection of Refugees and Migrants in Refugee Accommodation Centres and provides a catalogue of respective protective measures, the responsibility for refugee accommodation and protection lies with the sixteen federal states. This article therefore analyses the federal states’ existing legal provisions with regard to the implementation of special protection for LGBTI+ refugees. Relevant measures are examined in detail and clustered to highlight specific protection needs. In the period of observation, only nine out of sixteen federal states had set legal provisions. On average, these covered less than a third of the LGBTI+-specific protective measures laid out by the federal Minimum Standards. Keywords: LGBTI+ refugees; safety measures; anti-gay/anti-trans violence; asylum; gender- based discrimination

In the summer and fall of 2019, Battle Company, 1st Battalion, 32nd Infantry Regiment, 1st Brigade Combat Team, 10th Mountain Division, conducted an intense training cycle over the course of five months that included individual and collective training events and culminated with a decisive action rotation at the Joint Readiness Training Center (JRTC) at Fort Polk, LA. The rear detachment leader should receive training on basics of Global Combat Support System -Army (GCSS-Army) and property management in order to enforce the Command Supply Discipline Program (CSDP). Attention to detail was extremely important as NCOs and Soldiers identified Bll/obscure items that were hard to understand from a picture in a technical manual (TM). [...]the team leaders sub-hand receipt the equipment to the end user (with heavy squad leader supervision).

This study examines the link between culture and ethical decision making in the context of international oil and gas operations. Specifically, this study examines the extent to which cultural differences influence oil and gas accountants' assessment of fraudulent business activities. The survey includes two fraudulent statement scenarios, one involving fraudulent financial statements and the other involving fraudulent non-financial statements. Overall, the respondents underrated the seriousness of these two scenarios with the ratings of the Asia-Pacific respondents being significantly lower than those of respondents from the other regions. The survey includes four corruption schemes, including economic extortion, illegal gratuity, conflict of interest, and bribery. Employee understanding of corruption schemes is particularly relevant to the provisions of the Foreign Corrupt Practices Act; however, respondents consistently assessed the corruption-related scenarios as being only moderately serious. The Asia-Pacific respondents consistently rated the schemes lower than did the respondents from the other regions. Nine scenarios involve asset misappropriation schemes. Overall the respondents assessed the scenarios involving cash register disbursement and check tampering schemes as involving highly serious fraudulent activities. The results indicate that cultural differences play a significant role in accountants' assessments of a variety of fraud-related activities, especially schemes involving corruption and asset misappropriation.

This chapter contains sections titled: Introduction Discovery of Maraviroc and PF‐232798 HTS and Biological Screening to Guide Medicinal Chemistry Discovery and Characterization of PF‐232798, A Second‐Generation CCR5 Antagonist Synthesis Nonclinical Safety and Toxicity Studies Phase I‐III Clinical PK Safety and Efficacy Evaluation of Maraviroc Resistance to Maraviroc in Clinical Trials: Observations and Implications Future Directions References

This chapter contains sections titled: Background and Rationale The Discovery of Maraviroc Preclinical Studies The Synthesis of Maraviroc Nonclinical Safety and Toxicity Studies Clinical Development of Maraviroc Summary, Future Directions, and Challenges Acknowledgments References

Dorr reviews Can the World Afford Autistic Spectrum Disorder? Nonverbal Communication, Asperger Syndrome and the Interbrain by Digby Tantam.

In the Tax Reform Act, Congress added Internal Revenue Code (IRC) Section 280F with provisions imposing significant limitations on the amount of investment tax credit (ITC) and depreciation that may be claimed for property used partially for personal reasons and partly for business purposes. Property not used over 50% for business will not qualify for accelerated depreciation or ITC. In addition, employee business use must be for the convenience of the employer and required as a condition of employment. Special limitations apply to automobiles in the area of depreciation, and the ITC for a passenger automobile may not exceed $1,000. Both limits must also be reduced by the personal use percentage. Other provisions of IRC Section 280F involve: 1. employer-purchased property, 2. leasing arrangements, 3. recapture of tax benefits, and 4. record-keeping requirements. Additional regulations have been issued to ease the original contemporaneous records requirements for automobiles and trucks.