Prevalence and Genotype Distribution of HPV in Cytology Specimens Containing Atypical Glandular Cells: A Case Control Study

Introduction: Although the incidence of squamous cell cervical cancers in the U.S. has markedly declined over time with the introduction of the Papanicolaou (Pap) test, the incidence of glandular cell cancers has increased. The sensitivity of detecting lesions containing abnormal glandular cells is much lower than that for lesions containing abnormal squamous cells. While AGC-grade cytology results represent \u3c1% of all Pap test results reported annually in the U.S., up to 40% of them represent a corresponding high-grade lesion on the followup biopsy. Guidelines for managing AGC-grade cytology released in 2006 by the American Society for Colposcopy and Cervical Pathology include HPV testing. The purpose of this study was to determine the prevalence and genotype distribution of HPV in AGC-grade liquid-based cytology (LBC) specimens compared to control specimens negative for intraepithelial lesion or malignancy (NILM). Methods: Quest Diagnostics provided de-identified case and control LBC specimens. Cases were women with AGC-grade LBC specimens collected between 2007- 2012. Controls were a sample of women with NILM-grade LBC specimens collected between 2011-2012. DNA was extracted from LBC specimens using the QIAamp MinElute Media Kit (Qiagen Inc.) and amplified by PCR using the Linear Array HPV Genotyping Kit (Roche Molecular Inc.). To compare HPV prevalence and genotype distribution between AGC-grade cases and NILM controls, we used multivariate logistic regression to generate age-adjusted odds ratios (ORadj) and 95% confidence intervals (CI). Results: Fifty-three AGC-grade LBC specimens (mean age; 57 yrs, age range; 18-95 yrs) and 338 NILM LBC specimens (mean age; 45 yrs, age range; 20-91 yrs) were screened for 37 types of HPV DNA: 13 high-risk (HR) HPV types and 24 low-risk (LR) HPV types. Any HR-HPV was present in 34% of AGC-grade specimens and 7.4% of NILM specimens (ORadj=9.11; 95% CI: 4.08-20.33, p-value\u3c0.001). When limited to HPV 16/18, at least one was present in 20.1% of AGC-grade specimens and 1.2% of NILM specimens (ORadj=40.10, 95% CI: 10.73- 149.88, p-value\u3c0.001). In contrast, prevalence of low-risk (LR) HPV was similar between the two groups: 15% of AGC-grade specimens and 17.2% of NILM specimens (ORadj=0.91; 95% CI: 0.35-2.31, p-value=0.834). Conclusion: AGC-grade specimens were found to contain a significantly higher rate of HR-HPV, especially HPV types 16 or 18 when compared to NILM specimens. These findings support the earlier recommendation that HPV testing should be performed on LBC specimens with AGC-grade diagnosis and suggests that genotyping may be a useful addition to the follow up testing being performed

Staphylococcus aureus Nasal Carriage among Beefpacking Workers in a Midwestern United States Slaughterhouse

Occupational contact with livestock is an established risk factor for exposure to livestock-associated methicillin-resistant Staphylococcus aureus (MRSA), particularly among industrial swine workers. While S. aureus is known to infect cattle, livestock-associated S. aureuscarriage among workers in the beef production chain has received limited attention. Beefpacking workers, who slaughter, butcher and process cattle, have intensified exposure to potentially infectious animal materials and may be at risk of livestock-associated S. aureusexposure. We conducted a cross-sectional study of beefpacking workers (n = 137) at an industrial slaughterhouse in the Midwestern United States to evaluate prevalence and characteristics of S. aureus nasal colonization, specifically the absence of the scn gene to identify putative association with livestock, antibiotic susceptibility, presence of Panton-Valentin leukocidin (PVL) genes lukS-PV and lukF-PV, and spa type. Overall prevalence of S.aureus nasal carriage was 27.0%. No workers carried livestock-associated MRSA. Methicillin-sensitive S. aureus isolates (MSSA) recovered from five workers (3.6%) lacked the scn gene and were considered putative livestock-associated S. aureus (pLA-SA). Among pLA-SA isolates, spa types t338, t748, t1476 and t2379 were identified. To our knowledge, these spatypes have not previously been identified as associated with livestock. Prevalence of human-adapted MRSA carriage in workers was 3.6%. MRSA isolates were identified as spa types t002, t008 and t024, and four of five MRSA isolates were PVL-positive. To date, this is the first study to indicate that industrial beefpacking workers in the United States may be exposed to livestock-associated S. aureus, notably MSSA, and to spa types not previously identified in livestock and livestock workers. Occupational exposure to livestock-associated S. aureus in the beef production chain requires further epidemiologic investigation

The Ursinus Weekly, March 5, 1951

Helfferich retains MAC title; Voted outstanding • Music Club lists HMS Pinafore as Spring production • Community Chest receives support • MSGA holds discussion on guests\u27 meal prices • Brownback receives material for May 4, 5 grad record exam • Dr. McClure to view Ursinus problems at YM-YWCA meeting • Group presentation of Condemned scores hit • DuPont lecturer shows new super light plastic • Larry Livingston, DuPont manager, to speak here • Dr. Yost to read poetry of Edna St. Vincent Millay • Administration receives additional data on draft • Seniors\u27 original Speak Easy ready for production • Lantern staff prepares issue; Meeting called • Notecrackers lose coin-tossing finals • Charles Lachman donates rug for Library faculty room • Red Cross drive begins • Rushing starts Monday • Editorial: Participation makes spirit; Support Red Cross; Lenten thoughts • L-shaped office is language office, where all is congeniality, cooperation, cordiality • Star gazers view sky, map moon through telescope atop Pfahler Hall • Staff grinds out The Weekly midst daily confusion • Swarthmore knocks Ursinus quintet from league contention in 78-56 win • Jerry Seeders awaits word on call to Army; Was captain in last war • Quintet winds up season in 95-62 loss to Blue Hens • Bear matmen rally, tie Drexel 14-14 • Belles defeat Penn to stay unbeaten • Mermaids capture fourth place in district intercollegiate meet • Club holds supperhttps://digitalcommons.ursinus.edu/weekly/1561/thumbnail.jp

The Ursinus Weekly, November 13, 1950

Fraternities fete, bid men during week of rushing • First movies of year, Little Men, Great Guns, to be shown on Friday • Debaters to oppose Swarthmore varsity • Lantern asks students for Fall issue material • Herbsleb to address IRC Tuesday on international law topic • Chi Alpha to meet Tuesday • 51\u27ers assume commercial name • Smith tells Forum of status of Britain in trade, economy • Ruby launches campaigns for photography and selling • Student authored, produced Dusty Halo receives plaudits • YM-YW conducts WSSF and toy-clothing drives • Harris stresses need of developing maturity in religious matters • Dorm at 724 Main wins spirit trophy • Sophs to send gift to injured classmate • Big Sisters hold party • Editorials: Case against apathy; Challenge to our intellect • Class idiosyncrasies bared • Scribe pens WSGA notes • Drum majorettes use many maneuvers, combine long experience and ingenuity • Committee heads announced for Curtain Club Fall production • MSGA to cut mealtime announcements, substitute rebuilt outdoor bulletin board • Newman Club holds banquet • Beaver falls 3-2 to hockey squad; Boyd paces team • Jay-Vees triumph 6-1 over Beaver JV squad • Bruins to oppose Crusaders eleven at Selinsgrove • Grizzlies bow 3-0 to Lehigh booters • Undefeated Derr cops intramural grid title • Panthers build early lead to conquer Bruins 13-6 • St. Joseph\u27s takes cross-country meet • Cheer and comfort for the weary, tale of mid-semester\u27s evil birth • Weekly sports poll reveals majority wants powerhouse intercollegiate teamhttps://digitalcommons.ursinus.edu/weekly/1552/thumbnail.jp

Coherent signature of warming-induced extreme sub-continental boreal wildfire activity 4800 and 1100 years BP

Climate changes are expected to progressively increase extreme wildfire frequency in forests. Finding past analogs for periods of extreme biomass burning would provide valuable insights regarding what the effects of warming might be for tree species distribution, ecosystem integrity, atmospheric greenhouse gas balance, and human safety. Here, we used a network of 42 lake-sediment charcoal records across a ~2000 km transect in eastern boreal North America to infer widespread periods of wildfire activity in association with past climate conditions. The reconstructed fluctuations in biomass burning are broadly consistent with variations in ethane concentration in Greenland polar ice cores. Biomass burning fluctuations also significantly co-varied with Greenland temperatures estimated from ice cores, at least for the past 6000 years. Our retrospective analysis of past fire activity allowed us to identify two fire periods centered around 4800 and 1100 BP, coinciding with large-scale warming in northern latitudes and having respectively affected an estimated ~71% and ~57% of the study area. These two periods co-occurred with widespread decreases in mean fire-return intervals. The two periods are likely the best analogs for what could be anticipated in terms of impacts of fire on ecosystem services provided by these forests in coming decades

Risk of Parkinson's disease after tamoxifen treatment

<p>Abstract</p> <p>Background</p> <p>Women have a reduced risk of developing Parkinson's disease (PD) compared with age-matched men. Neuro-protective effects of estrogen potentially explain this difference. Tamoxifen, commonly used in breast cancer treatment, may interfere with the protective effects of estrogen and increase risk of PD. We compared the rate of PD in Danish breast cancer patients treated with tamoxifen to the rate among those not treated with tamoxifen.</p> <p>Methods</p> <p>A cohort of 15,419 breast cancer patients identified from the Danish Breast Cancer Collaborative Group database was linked to the National Registry of Patients to identify PD diagnoses. Overall risk and rate of PD following identification into the study was compared between patients treated with tamoxifen as adjuvant hormonal therapy and patients not receiving tamoxifen. Time-dependent effects of tamoxifen treatment on PD rate were examined to estimate the likely induction period for tamoxifen.</p> <p>Results</p> <p>In total, 35 cases of PD were identified among the 15,419 breast cancer patients. No overall effect of tamoxifen on rate of PD was observed (HR = 1.3, 95% CI: 0.64-2.5), but a PD hazard ratio of 5.1 (95% CI: 1.0-25) was seen four to six years following initiation of tamoxifen treatment.</p> <p>Conclusions</p> <p>These results provide evidence that the neuro-protective properties of estrogen against PD occurrence may be disrupted by tamoxifen therapy. Tamoxifen treatments may be associated with an increased rate of PD; however these effects act after four years, are of limited duration, and the adverse effect is overwhelmed by the protection against breast recurrence conferred by tamoxifen therapy.</p

Genomewide Association Studies of LRRK2 Modifiers of Parkinson's Disease.

OBJECTIVE: The aim of this study was to search for genes/variants that modify the effect of LRRK2 mutations in terms of penetrance and age-at-onset of Parkinson's disease. METHODS: We performed the first genomewide association study of penetrance and age-at-onset of Parkinson's disease in LRRK2 mutation carriers (776 cases and 1,103 non-cases at their last evaluation). Cox proportional hazard models and linear mixed models were used to identify modifiers of penetrance and age-at-onset of LRRK2 mutations, respectively. We also investigated whether a polygenic risk score derived from a published genomewide association study of Parkinson's disease was able to explain variability in penetrance and age-at-onset in LRRK2 mutation carriers. RESULTS: A variant located in the intronic region of CORO1C on chromosome 12 (rs77395454; p value = 2.5E-08, beta = 1.27, SE = 0.23, risk allele: C) met genomewide significance for the penetrance model. Co-immunoprecipitation analyses of LRRK2 and CORO1C supported an interaction between these 2 proteins. A region on chromosome 3, within a previously reported linkage peak for Parkinson's disease susceptibility, showed suggestive associations in both models (penetrance top variant: p value = 1.1E-07; age-at-onset top variant: p value = 9.3E-07). A polygenic risk score derived from publicly available Parkinson's disease summary statistics was a significant predictor of penetrance, but not of age-at-onset. INTERPRETATION: This study suggests that variants within or near CORO1C may modify the penetrance of LRRK2 mutations. In addition, common Parkinson's disease associated variants collectively increase the penetrance of LRRK2 mutations. ANN NEUROL 2021;90:82-94

Finishing the euchromatic sequence of the human genome

The sequence of the human genome encodes the genetic instructions for human physiology, as well as rich information about human evolution. In 2001, the International Human Genome Sequencing Consortium reported a draft sequence of the euchromatic portion of the human genome. Since then, the international collaboration has worked to convert this draft into a genome sequence with high accuracy and nearly complete coverage. Here, we report the result of this finishing process. The current genome sequence (Build 35) contains 2.85 billion nucleotides interrupted by only 341 gaps. It covers ∼99% of the euchromatic genome and is accurate to an error rate of ∼1 event per 100,000 bases. Many of the remaining euchromatic gaps are associated with segmental duplications and will require focused work with new methods. The near-complete sequence, the first for a vertebrate, greatly improves the precision of biological analyses of the human genome including studies of gene number, birth and death. Notably, the human enome seems to encode only 20,000-25,000 protein-coding genes. The genome sequence reported here should serve as a firm foundation for biomedical research in the decades ahead