Background: Considering regional and temporal trends, we sought to explore the incidence of primary malignant brain tumours in Newfoundland and Labrador. Methods: We reviewed all primary, malignant brain tumour cases from 2015-2022 confirmed by St. John’s Health Sciences Centre pathology reports. Incidence rates were standardized using the 2011 Canadian standard population. Results: We included 362 cases. The average annual age-standardized incidence rate of primary, malignant brain tumours per 100,000 was 7.0 (95% CI: 6.3-7.7), lower than the national average (7.93; 95% CI: 7.78-8.08). The incidence of glioblastoma (5.1; 95% CI: 4.5-5.7) was significantly higher than the national average (4.05; 95% CI: 3.95-4.16). Temporal trends revealed that oligodendroglioma incidence spiked from 0.5 (95% CI: 0.2-0.7) in 2015-2019 to 1.5 (95% CI: 0.4-2.6) in 2020 before returning to baseline in 2022. Regional trends indicated a lower incidence of malignant tumours in Labrador-Grenfell (5.1; 95% CI: 2.5-7.6), compared to 6.9 (95% CI: 6.2-7.6) averaged elsewhere. Conclusions: Higher rates of glioblastoma in Newfoundland and Labrador could have a genetic or multi-factorial cause. The increased occurrence of oligodendroglioma during the COVID-19 pandemic necessitates broader investigation, potentially linked to delays in patient care during this period. Regional trends could suggest less access to care in rural populations and underestimated incidence.

Background: Brain metastases indicate an advanced tumour stage for many cancers. We sought to investigate the incidence change of tissue-sampled brain metastases and its relation to staging challenges during the COVID-19 pandemic in Newfoundland and Labrador. Methods: We reviewed all brain metastasis cases from 2015-2022 requiring first-time tissue sampling according to pathology reports from the St. John’s Health Sciences Centre. Incidence rates were calculated using yearly population data by regional health authorities and standardized using the 2011 Canadian standard population. Results: We included 173 cases. The average annual age-standardized incidence rate of brain metastases requiring tissue sampling per 100,000 increased from 2.5 (95% CI: 2.0-3.1) pre-COVID-19 to 4.1 (95% CI: 3.3-5.0) post-COVID-19. Brain metastases from lung primaries accounted for 69% of this increase. While incidence declined to near-baseline in the Eastern provincial population by 2022 (3.3; 95% CI: 1.5-5.1), incidence rose into 2022 in the Western population (8.6; 95% CI: 3.9-13.2). Conclusions: These data suggest a delayed presentation of malignancies during the COVID-19 pandemic and underscore the importance of prioritized staging during times of strain on healthcare systems. Regional, temporal trends suggest regions distant from tertiary care centres could face challenges in resolving cases with delayed presentation post-COVID-19.

OBJECTIVES/GOALS: Mayo Clinic (MC) launched the Rapid Activation Trial (RAT) pilot program in 2022 to expedite the activation of high priority and high impact clinical trials. The objective was to develop a process for rapid activation through robust screening, prioritization, and project management (PM) support. METHODS/STUDY POPULATION: The project team developed a robust screening and approval process for the RAT program using a combination of an objective scoring tool (based on strategic priorities) and a diverse selection committee to screen and approve eligible trials. Sponsors had to commit to RAT program timelines. Upon approval, trials were prioritized at the highest level within each business unit involved in the activation process. The number of trials approved annually were limited to 8 to manage volume and facilitate seamless prioritization with an activation timeline goal of 6 weeks. Project management support for RAT program focused on financial, regulatory, logistical, and operational elements to open trials expeditiously. RESULTS/ANTICIPATED RESULTS: In 2022, thirteen (13) applications were received and eight (8) were approved by the RAT selection committee. The approved trials activated with a median open to enrollment time of 6.4 weeks from engaging with business units. They also aligned closely with organization’s strategic priorities, including but not limited to Investigator Initiated Trials, Multi-Site protocols, IND/IDE protocols, Rare Diseases, First in Human and Commercialization potential trials. PI and study team feedback was positive. In 2023, the RAT program was renewed due to the pilot’s significant success in 2022. The goal is to open 10 trials and 5 have been activated by the end of Q3, 2023 with a median timeline of 6 weeks. DISCUSSION/SIGNIFICANCE: Rapid activation of high priority and high impact clinical trials enables an organization to strategically prioritize and open complex clinical trials. This allows the delivery of innovative, timely cures to patients in an expeditious timeline.

Health technology assessment (HTA) agencies are considering adopting a lifecycle approach to assessments to address uncertainties in the evidence base at launch and to revisit the clinical and economic value of therapies in a dynamic clinical landscape. For reassessments of therapies post launch, HTA agencies are looking to real-world evidence (RWE) to enhance the clinical and economic evidence base, though challenges and concerns in using RWE in decision-making exists. Stakeholders are embarking on demonstration projects to address the challenges and concerns and to further define when and how RWE can be used in HTA decision making. The Institute for Clinical and Economic Review piloted a 24-month observational RWE reassessment. Key learnings from this pilot include identifying the benefits and challenges with using RWE in reassessments and considerations on prioritizing and selecting topics relevant for RWE updates.

We examined the item properties of the Two Peas Questionnaire (TPQ) among a sample of same-sex twin pairs from the Washington State Twin Registry. With the exception of the ‘two peas’ item, three of the mistakenness items showed differential item functioning. Results showed that the monozygotic (MZ) and dizygotic (DZ) pairs may differ in their responses on these items, even among those with similar latent traits of similarity and confusability. Upon comparing three classification methods to determine the zygosity of same-sex twins, the overall classification accuracy rate was over 90% using the unit-weighted pair zygosity sum score, providing an efficient and sufficiently accurate zygosity classification. Given the inherent nature of twin-pair similarity, the TPQ is more accurate in the identification of MZ than DZ pairs. We conclude that the TPQ is a generally accurate, but by no means infallible, method of determining zygosity in twins who have not been genotyped.

It has been over 5 years since the last special issue of Twin Research and Human Genetics on ‘Twin Registries Worldwide: An Important Resource for Scientific Research’ was published. Much progress has been made in the broad field of twin research since that time, and the current special issue is a follow-up to update the scientific community about twin registries around the globe. The present article builds upon our 2013 Registry description by summarizing current information on the Washington State Twin Registry (WSTR), including history and construction methods, member characteristics, available data, and major research goals. We also provide a section with brief summaries of recently completed studies and discuss the future research directions of the WSTR. The Registry has grown in terms of size and scope since 2013; highlights include recruitment of youth pairs under 18 years of age, extensive geocoding work to develop environmental exposures that can be linked to survey and administrative health data such as death records, and expansion of a biobank with specimens collected for genotyping, DNA methylation, and microbiome based-studies.

Approximately 12% of U.S. adults have type 2 diabetes (T2D). Diagnosed T2D is caused by a combination of genetic and environmental factors including age and lifestyle. In adults 45 years and older, the Discordant Twin (DISCOTWIN) consortium of twin registries from Europe and Australia showed a moderate-to-high contribution of genetic factors of T2D with a pooled heritability of 72%. The purpose of this study was to investigate the contributions of genetic and environmental factors of T2D in twins 45 years and older in a U.S. twin cohort (Washington State Twin Registry, WSTR) and compare the estimates to the DISCOTWIN consortium. We also compared these estimates with twins under the age of 45. Data were obtained from 2692 monozygotic (MZ) and same-sex dizygotic (DZ) twin pairs over 45 and 4217 twin pairs under 45 who responded to the question ‘Has a doctor ever diagnosed you with (type 2) diabetes?’ Twin similarity was analyzed using both tetrachoric correlations and structural equation modeling. Overall, 9.4% of MZ and 14.7% of DZ twins over the age of 45 were discordant for T2D in the WSTR, compared to 5.1% of MZ and 8% of DZ twins in the DISCOTWIN consortium. Unlike the DISCOTWIN consortium in which heritability was 72%, heritability was only 52% in the WSTR. In twins under the age of 45, heritability did not contribute to the variance in T2D. In a U.S. sample of adult twins, environmental factors appear to be increasingly important in the development of T2D.

Objective: While individuals with 22q11.2 deletion syndrome (22q11DS) are at increased risk for a variety of functional impairments and psychiatric disorders, including psychosis, not all individuals with 22q11DS experience negative outcomes. Efforts to further understand which childhood variables best predict adult functional outcomes are needed, especially those that investigate childhood executive functioning abilities. Methods: This longitudinal study followed 63 individuals with 22q11DS and 43 control participants over 9 years. Childhood executive functioning ability was assessed using both rater-based and performance-based measures and tested as predictors of young adult outcomes. Results: Childhood global executive functioning abilities and parent report of child executive functioning abilities were the most consistent predictors of young adult outcomes. The study group moderated the relationship between child executive functioning and young adult outcomes for several outcomes such that the relationships were stronger in the 22q11DS sample. Conclusion: Rater-based and performance-based measures of childhood executive functioning abilities predicted young adult outcomes in individuals with and without 22q11DS. Executive functioning could be a valuable target for treatment in children with 22q11DS for improving not only childhood functioning but also adult outcomes. (JINS, 2018, 24, 905–916)

BACKGROUND: IGTS is a rare phenomenon of paradoxical germ cell tumor (GCT) growth during or following treatment despite normalization of tumor markers. We sought to evaluate the frequency, clinical characteristics and outcome of IGTS in patients in 21 North-American and Australian institutions. METHODS: Patients with IGTS diagnosed from 2000-2017 were retrospectively evaluated. RESULTS: Out of 739 GCT diagnoses, IGTS was identified in 33 patients (4.5%). IGTS occurred in 9/191 (4.7%) mixed-malignant GCTs, 4/22 (18.2%) immature teratomas (ITs), 3/472 (0.6%) germinomas/germinomas with mature teratoma, and in 17 secreting non-biopsied tumours. Median age at GCT diagnosis was 10.9 years (range 1.8-19.4). Male gender (84%) and pineal location (88%) predominated. Of 27 patients with elevated markers, median serum AFP and Beta-HCG were 70 ng/mL (range 9.2-932) and 44 IU/L (range 4.2-493), respectively. IGTS occurred at a median time of 2 months (range 0.5-32) from diagnosis, during chemotherapy in 85%, radiation in 3%, and after treatment completion in 12%. Surgical resection was attempted in all, leading to gross total resection in 76%. Most patients (79%) resumed GCT chemotherapy/radiation after surgery. At a median follow-up of 5.3 years (range 0.3-12), all but 2 patients are alive (1 succumbed to progressive disease, 1 to malignant transformation of GCT). CONCLUSION: IGTS occurred in less than 5% of patients with GCT and most commonly after initiation of chemotherapy. IGTS was more common in patients with IT-only on biopsy than with mixed-malignant GCT. Surgical resection is a principal treatment modality. Survival outcomes for patients who developed IGTS are favourable.

Presented here are quantitative dissolution rate data (volume of pyrite lost/time) for the inorganic oxidation of pyrite in synthetic, anaerobic and acidic (pH 2) hydrothermal vent fluids (HVF) from experiments where the volume loss was measured directly via Vertical Scanning Interferometry (VSI). The VSI-derived reaction rate was 2.12x10-10±1.14x10-1 mol/m2/min, which is ∼2 to 4 orders of magnitude slower than pyrite oxidation rates previously determined using traditional batch experiments where rates are calculated based on changes in solution chemistry. This lower rate stems primarily from differences in experimental conditions (i.e. water to rock ratios, vigorous vs. gentle stir rates, grain-size effects, time), yet the rates derived here are believed to be more representative of pyrite oxidation in natural environments where more static and high solution to solid rate conditions prevail, such as seafloor conditions or acid-mine-drainage environments.

We examined risk factors associated with the intestinal acquisition of antimicrobial-resistant extraintestinal pathogenic Escherichia coli (ExPEC) and development of community-acquired urinary tract infection (UTI) in a case-control study of young women across Canada. A total of 399 women were recruited; 164 women had a UTI caused by E. coli resistant to ⩾1 antimicrobial classes and 98 had a UTI caused by E. coli resistant to ⩾3 antimicrobial classes. After adjustment for age, student health service (region of Canada) and either prior antibiotic use or UTI history, consumption of processed or ground chicken, cooked or raw shellfish, street foods and any organic fruit; as well as, contact with chickens, dogs and pet treats; and travel to Asia, were associated with an increased risk of UTI caused by antimicrobial resistant E. coli. A decreased risk of antimicrobial resistant UTI was associated with consumption of apples, nectarines, peppers, fresh herbs, peanuts and cooked beef. Drug-resistant UTI linked to foodborne and environmental exposures may be a significant public health concern and understanding the risk factors for intestinal acquisition of existing or newly emerging lineages of drug-resistant ExPEC is important for epidemiology, antimicrobial stewardship and prevention efforts.

I would be remiss if I did not begin by admitting my sheer delight to see organizational scientists (e.g., Hall, Hall, & Perry, 2016; Ruggs et al., 2016) taking a greater interest in broader societal social issues like these. In 2007, when I was the chair of the Society for Industrial and Organizational Psychology's (SIOP's) Committee for Ethnic Minority Affairs (CEMA), I devoted part of a column in The Industrial–Organizational Psychologist to discussing what I perceived to be a law enforcement racial injustice perpetrated against several adolescents in Louisiana known as the “Jena Six” (Avery, 2007). The issue at hand in that case was the impact of race after an arrest was made. The media reports of the case at that time compelled many to believe that its handling by law enforcement and the criminal justice system had been influenced adversely by the racial composition of the White plaintiff and Black defendants. Like Ruggs et al., I felt then and continue to believe that we, as industrial–organizational (I-O) psychologists, could be doing more to redress societal injustice. I also commend them on the multifaceted nature of their discussion and appreciate that they highlighted a number of ways in which our existing knowledge base is, and future research products could be, pertinent to what's happening all too often between police and the minority communities they are intended to serve and protect.

Background: The etiology and treatment of pulsatile tinnitus is difficult and there are different causes for it. To our knowledge, an obstruction of the transverse sinus due to tentorial meningioma has not been reported. Methods: A 66 year old female presented a year ago with a sudden onset of a hissing sound in her ear which has persisted since. Neurologically she was intact. She was seen by otolaryngology who identified no cause for her tinnitus. A CT scan and MRI showed a tentorial meningioma on the right side with partial obstruction of the transverse sinus with evidence of partial chronic thrombus. Results: Removal of the meningioma with decompression of the transverse sinus resulted in immediate disappearance of the pulsatile tinnitus. Conclusions: This report can be added to the etiology of the difficult entity of pulsatile tinnitus particularly as it relates to its management.

Background: The occurrence of familial brain tumours, particularly gliomas, hemangioblastomas in Von Hippel Lindau and other endocrine neoplasia, is well documented in the literature. On the other hand, familial pineal tumours are extremely rare and only a handful of cases have been reported. Methods and Results: Two female siblings presented at ages 12 and 15 with histories of progressive headaches. Neurological examination in each was completely normal. Magnetic Resonance Imaging confirmed the presence of cystic and solid lobulated pineal lesions with mild enhancement, consistent with pineocytoma, in both girls. Follow-up for 15 years in the first sibling and 4 years in the second showed no evolution in radiological or clinical manifestations. No active treatments have been carried out. Conclusion: The occurrence of familial pineal lesions raises the possibility of a close relationship between heredity and oncogenicity, and should be further explored.

We surveyed infection prevention programs in 16 hospitals for hospital-associated methicillin-resistant Staphylococcus aureus (MRSA), vancomycin-resistant enterococci, extended-spectrum β-lactamase, and multidrug-resistant Acinetobacter acquisition, as well as hospital-associated MRSA bacteremia and Clostridium difficile infection based on defining events as occurring >2 days versus >3 days after admission. The former resulted in significantly higher median rates, ranging from 6.76% to 45.07% higher

Infect Control Hosp Epidemiol 2014;35(11):1417–1420