In-Flight Transmission of a SARS-CoV-2 Lineage B.1.617.2 Harbouring the Rare S:E484Q Immune Escape Mutation.

We describe a flight-associated infection scenario of seven individuals with a B.1.617.2 (Delta) lineage, harbouring an S:E484Q point mutation. In Sweden, at least 10% of all positive SARS-CoV-2 samples were sequenced in each county; the B.1.717.2 + S:E484Q combination was not detected in Sweden before and was imported within the scenario described in this report. The high transmission rate of the delta lineage combined with the S:E484Q mutation, associated with immune escape in other lineages, makes this specific genetic combination a possible threat to the global fight against the COVID-19 pandemic. Even within the Omicron wave, the B.1.617.2 + S:E484Q variant appeared in community samples in Sweden, as it seems that this combination has an evolutionary gain compared to other B.1.617.2 lineages. The here described genomic combination was not detectable with the common fasta file-based Pango-lineage analysis, hence increasing the probability of the true global prevalence to be higher.

Trends in medical conditions and functioning in the U.S. population, 1997-2017.

BACKGROUND: Over the last several decades, the federal disability rolls grew substantially, though this growth has slowed more recently. Many factors underlie these trends, including changes in demographics, policies, and disability prevalence. OBJECTIVE: We address two research questions: (1) How has the prevalence of certain potentially disabling conditions changed among working-age adults over the last two decades? and (2) Among individuals with these conditions, how has the share who report particular functional limitations changed over time? METHODS: We use nationally representative survey data from the National Health Interview Survey (NHIS) to document regression adjusted population trends since 1997 in some of the most commonly disabling chronic conditions and functional limitations among adult disability beneficiaries. RESULTS: We find that the prevalence of several conditions has increased in the U.S. population - most notably, obesity, endocrine conditions, and neoplasms. We also find notable changes in functional limitations. Hearing and vision limitations declined, while adults experienced increases in cognitive, social, and movement limitations. Alongside these long-term trends we find some evidence that reporting of conditions and limitations is countercyclical with the business cycle. CONCLUSIONS: These changes in condition prevalence and functional limitations are consistent with some but not all documented changes in the federal disability rolls. Increases in social limitations are consistent with the perception that Americans are increasingly socially isolated.

Access to care and health insurance coverage for workers with disabilities: Outcomes by state-level responses to the ACA.

BACKGROUND: States had flexibility in their implementation of the Patient Protection and Affordable Care Act (ACA) Medicaid expansions, which may have led to variation in coverage and changes in access to care for workers with disabilities. OBJECTIVE/HYPOTHESIS: To examine differential trends in health insurance coverage and access to care among workers with disabilities by states' decisions about expanding Medicaid under the ACA. METHODS: We aggregated data from the National Health Interview Survey into groups by time period relative to ACA implementation: pre-ACA (2006-2009), early ACA (2010-2013), and later ACA (2014-2017). We produced health insurance and access statistics for each time period, by state-level Medicaid expansion status. RESULTS: Uninsurance rates decreased after 2014 in all states, regardless of the state's decision whether to expand Medicaid. There was a substantial increase after 2014 in the share of workers with disabilities covered by Medicaid in states that expanded in that year; in other states, workers with disabilities experienced larger increases in privately purchased coverage. At the same time, the share of workers with disabilities reporting cost-related barriers to care declined markedly in 2014 Medicaid expansion states, but it increased slightly in the non-expansion states. Structural barriers to accessing care increased in all states, with the smallest increase in 2014 expansion states. CONCLUSIONS: Medicaid coverage and cost-related access to care improved significantly among workers with disabilities in 2014 Medicaid expansion states, both overall and relative to workers with disabilities in non-expansion states.

Variant SARS-CoV-2 mRNA vaccines confer broad neutralization as primary or booster series in mice.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is the causative agent of a global pandemic. Safe and effective COVID-19 vaccines are now available, including mRNA-1273, which has shown 94% efficacy in prevention of symptomatic COVID-19 disease. However, the emergence of SARS-CoV-2 variants has led to concerns of viral escape from vaccine-induced immunity. Several variants have shown decreased susceptibility to neutralization by vaccine-induced immunity, most notably B.1.351 (Beta), although the overall impact on vaccine efficacy remains to be determined. Here, we present the initial evaluation in mice of 2 updated mRNA vaccines designed to target SARS-CoV-2 variants: (1) monovalent mRNA-1273.351 encodes for the spike protein found in B.1.351 and (2) mRNA-1273.211 comprising a 1:1 mix of mRNA-1273 and mRNA-1273.351. Both vaccines were evaluated as a 2-dose primary series in mice; mRNA-1273.351 was also evaluated as a booster dose in animals previously vaccinated with mRNA-1273. The results demonstrated that a primary vaccination series of mRNA-1273.351 was effective at increasing neutralizing antibody titers against B.1.351, while mRNA-1273.211 was effective at providing broad cross-variant neutralization. A third (booster) dose of mRNA-1273.351 significantly increased both wild-type and B.1.351-specific neutralization titers. Both mRNA-1273.351 and mRNA-1273.211 are being evaluated in pre-clinical challenge and clinical studies.

Safety and immunogenicity of SARS-CoV-2 variant mRNA vaccine boosters in healthy adults: an interim analysis.

The emergence of SARS-CoV-2 variants of concern (VOCs) and variants of interest (VOIs) with decreased susceptibility to neutralization has generated interest in assessments of booster doses and variant-specific vaccines. Clinical trial participants who received a two-dose primary series of the COVID-19 vaccine mRNA-1273 approximately 6 months earlier entered an open-label phase 2a study ( NCT04405076 ) to evaluate the primary objectives of safety and immunogenicity of a single booster dose of mRNA-1273 or variant-modified mRNAs, including multivalent mRNA-1273.211. As the trial is currently ongoing, this exploratory interim analysis includes preliminary descriptive results only of four booster groups (n = 20 per group). Immediately before the booster dose, neutralizing antibodies against wild-type D614G virus had waned (P < 0.0001) relative to peak titers against wild-type D614G measured 1 month after the primary series, and neutralization titers against B.1.351 (Beta), P.1 (Gamma) and B.1.617.2 (Delta) VOCs were either low or undetectable. Both the mRNA-1273 booster and variant-modified boosters were safe and well-tolerated. All boosters, including mRNA-1273, numerically increased neutralization titers against the wild-type D614G virus compared to peak titers against wild-type D614G measured 1 month after the primary series; significant increases were observed for mRNA-1273 and mRNA-1273.211 (P < 0.0001). In addition, all boosters increased neutralization titers against key VOCs and VOIs, including B.1.351, P.1. and B.1.617.2, that were statistically equivalent to peak titers measured after the primary vaccine series against wild-type D614G virus, with superior titers against some VOIs. This trial is ongoing.

Variant SARS-CoV-2 mRNA vaccines confer broad neutralization as primary or booster series in mice.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is the causative agent of a global pandemic. Safe and effective COVID-19 vaccines are now available, including mRNA-1273, which has shown 94% efficacy in prevention of symptomatic COVID-19 disease. However, the emergence of SARS-CoV-2 variants has led to concerns of viral escape from vaccine-induced immunity. Several variants have shown decreased susceptibility to neutralization by vaccine-induced immunity, most notably B.1.351 (Beta), although the overall impact on vaccine efficacy remains to be determined. Here, we present the initial evaluation in mice of 2 updated mRNA vaccines designed to target SARS-CoV-2 variants: (1) monovalent mRNA-1273.351 encodes for the spike protein found in B.1.351 and (2) mRNA-1273.211 comprising a 1:1 mix of mRNA-1273 and mRNA-1273.351. Both vaccines were evaluated as a 2-dose primary series in mice; mRNA-1273.351 was also evaluated as a booster dose in animals previously vaccinated with mRNA-1273. The results demonstrated that a primary vaccination series of mRNA-1273.351 was effective at increasing neutralizing antibody titers against B.1.351, while mRNA-1273.211 was effective at providing broad cross-variant neutralization. A third (booster) dose of mRNA-1273.351 significantly increased both wild-type and B.1.351-specific neutralization titers. Both mRNA-1273.351 and mRNA-1273.211 are being evaluated in pre-clinical challenge and clinical studies.

Insurance coverage and access to care for workers with disabilities, 2001-2017.

BACKGROUND: Workers with disabilities have different options than their peers for obtaining health insurance, and face unique barriers in accessing care. The Patient Protection and Affordable Care Act (ACA) led to sweeping changes in the availability and affordability of health insurance in the United States beginning in 2010, and may have had important effects for workers with disabilities. OBJECTIVE/HYPOTHESIS: Document how the ACA changed insurance coverage and access to care for workers with disabilities, and compare those changes to changes among other groups. METHODS: We document health insurance coverage and access to care among workers with disabilities using the 2001-2017 National Health Interview Survey. RESULTS: The share of insured workers with disabilities increased from 79.9% in 2009 to 87.8% in 2017. This gain resulted from an 11 percentage point (pp) increase in the share with Medicaid coverage in 2014-2017 compared with 2001-2009 and a 5 pp increase in privately purchased coverage over those periods. These were accompanied by an 11 pp decline in the share with employer-sponsored coverage. Despite coverage gains, cost-related barriers to accessing medical care did not change much after the ACA, for any group. Workers with disabilities experienced an increase in structural access barriers, from 18.4% before the ACA to 24.8% after. CONCLUSIONS: The gain in insurance coverage for workers with disabilities is an important benefit of the ACA, but more investigation and monitoring should be considered to understand whether such coverage will translate into improvements in access to needed health care.

Oakland's sugar-sweetened beverage tax: Impacts on prices, purchases and consumption by adults and children.

Several cities in the U.S. have implemented taxes on sugar-sweetened beverages (SSBs) in an attempt to improve public health and raise revenue. On July 1, 2017, Oakland introduced a tax of one cent per ounce on SSBs. In this paper, we estimate the impact of the tax on retail prices, product availability, purchases, and child and adult consumption of taxed beverages in Oakland, as well as of potential substitute beverages. We collected data from Oakland stores and their customers and a matched group of stores in surrounding counties and their customers. We collected information in the months prior to the implementation of the tax and again a year later on: (1) prices, (2) purchase information from customers exiting the stores, and (3) a follow-up household survey of adults and child beverage purchases and consumption. We use a difference-in-differences identification strategy to estimate the impact of the tax on prices, purchases, and consumption of taxed beverages. We find that roughly 60 percent of the tax was passed on to consumers in the form of higher prices. There was a slight decrease in the volume of SSBs purchased per shopping trip in Oakland and a small increase in purchases at stores outside of the city, resulting in a decrease in purchases of 11.33 ounces per shopping trip that is not statistically significant. We find some evidence of increased shopping by Oakland residents at stores outside of the city. We do not find evidence of substantial changes in the overall consumption of SSBs or of added sugars consumed through beverages for either adults or children after the tax.

Comparative study of prophylaxis with high and low doses of voriconazole in children with malignancy.

BACKGROUND AND PURPOSE: Children with acute myeloid leukemia and relapses of leukemia are at high risk of developing fungal infections and need antifungal prophylaxis. This study aimed to compare the efficacy and toxicity of two different dosage regimens of voriconazole (VRC) during prophylactic administration in children with malignancy and neutropenia. MATERIALS AND METHODS: This prospective study was conducted at the Belarusian Research Center for Pediatric Oncology, Hematology, and Immunology from May 2017 to December 2019. The present study included 21 Caucasian patients with malignant hematological diseases (20 patients with acute myeloid leukemia and relapses of leukemia and 1 patient with Non-Hodgkin's lymphoma) aged 2-18 years. All patients were randomly divided into two groups that received different dosage regimens of VRCZ prophylaxis. Patients in the "high-dose" group received VRCZ at a dose of 9 mg/kg twice a day PO, or 8 mg/kg twice a day IV without a loading dose (children of 2-11 and adolescents and of 12-14 years old with <50 kg weight body), or a dose of 4 mg/kg twice a day PO or IV (adolescents of 12-14 years old with ≥50 kg body weight and all adolescents over 14 years old). Patients in the "low-dose" group received VRCZ at a dose of 4 mg/kg twice a day, PO or IV, without a loading dose (children of 2-11 and adolescents of 12-14 years old with <50 kg body weight), or at a dose of 3 mg/kg twice a day, PO or IV (adolescents of 12-14 years old with ≥ 50 kg body weight and all adolescents over 14 years old). When neutropenia recurred (after the next chemotherapy block), the patients were re-randomized and prophylaxis was resumed in the absence of fungal infection. Therefore, some patients (n=12, 57%) entered the study several times (maximum four times, after each chemotherapy block). In total, 21 patients experienced 40 episodes of VRCZ prophylaxis. RESULTS: In the high-dose group (n=20 episodes of prophylaxis), invasive fungal infections (IFI) signs were recorded in one (5%) case. In the low-dose group (n=20 episodes), IFI signs were observed in six (30%) cases (P=0.0375). The residual serum concentration was significantly higher in patients who received high doses of VRCZ (P<0.0001). Most patients with IFI (n=6, 86%) had a mean value (i.e., <0.74 µg/ml) of the residual serum concentration of the medication. Median of the first signs of fungal infection was 22 days from the start of prophylaxis. The dosage was the only highly significant factor that affected the metabolism of VRCZ. CONCLUSION: The likelihood of IFI was significantly lower in children who prophylactically received VRCZ in high doses (P=0.0375) and had ≥ 0.74 µg/ml residual serum concentration of the medication (P=0.0258). Residual serum concentration of VRCZ reached a plateau by day sixth of the treatment. In children, the dosage was the only highly significant factor affecting the metabolism of VRCZ.

The impact of the Philadelphia beverage tax on purchases and consumption by adults and children.

Numerous U.S. cities have recently enacted taxes on sweetened beverages. To examine the effects of the beverage tax of 1.5 cents per ounce in Philadelphia, we surveyed adults and children in Philadelphia and nearby comparison communities both before the tax and nearly one year after implementation. We find that the tax reduced purchases in Philadelphia stores and that Philadelphia residents increased purchases of taxed beverages outside of the city. The tax reduced the frequency of adults' soda consumption by 31 percent, but had no detectable impacts on adults' consumption of other beverages. The tax had no detectable impact on children's consumption of soda or all taxed beverages, although children who were frequent consumers prior to the tax reduced their consumption after the tax.

Invasion of an occupied niche by the crayfish Orconectes rusticus: potential importance of growth and mortality.

We are exploring mechanisms of an invasion that contradicts the oft-cited generalization that species invade vacant niches. In northern Wisconsin lakes, the introduced crayfish Orconectes rusticus is replacing two ecologically similar resident congeners, O. virilis and O. propinquus. In laboratory experiments, we compared growth and mortality of individually maintained crayfish offered one of five ad libitum diets: invertebrates, macrophytes, dentritus, periphyton or all items combined. Mortality was highest for O. virilis and lowest for O. rusticus. Macrophyte diets yielded the highest mortality. All three species grew best on invertebrate and combination diets but grew little or not at all on diets of periphyton, detritus or macrophytes. O. rusticus and O. virilis grew more than O. propinquus. O. rusticus grew more quickly and/or was better able to survive overall than its congeners. Therefore, O. rusticus would probably have advantages over O. virilis and O. propinquus in competitive interactions, reproductive success and avoiding size-selective fish predation. Subtle interspecific differences may interact strongly with other ecological factors and contribute to the displacement of resident species from a well-occupied niche.

Community-based participatory approach to reduce breast cancer disparities in south Dallas.

BACKGROUND: South Dallas experiences significant disparities in breast cancer mortality, with a high proportion of stage III and IV diagnoses. To address these rates, the Dallas Cancer Disparities Community Research Coalition created an educational intervention to promote breast health and early detection efforts. OBJECTIVES: The goals of the intervention were to increase (a) knowledge regarding the chief contributing factors for breast cancer, (b) awareness of the importance of screening for early detection, and (c) the proportion of women who have engaged in appropriate breast cancer screening practices. METHODS: Eligibility criteria for this nonrandomized, controlled trial included women age 40 and older, English-speaking, and having no personal history of cancer. Control participants received written breast health educational materials. Intervention participants attended 8 weekly sessions that included interactive educational materials, cooking demonstrations, and discussions emphasizing primary and secondary breast cancer prevention. All study participants completed a 1-hour survey at baseline and 4 months later. RESULTS: There were 59 women were enrolled in the intervention and 60 in the control group. At follow-up, after controlling for baseline mammography status, women in the intervention group were 10.4 times more likely (95% confidence interval [CI], 2.9-36.4) to have received a screening mammogram in the last year compared with the control group. Intervention participants demonstrated statistically significantly higher rates of breast self-examination (odds ratio [OR], 3.0; 95% CI, 1.0-8.6) and breast cancer knowledge (p=.003). CONCLUSION: Lessons learned from this community-based participatory research (CBPR) study can be used to create sustainable cancer disparity reduction models that can be replicated in similar communities.

Visual object memory and memory-guided saccades rely on shared mental representations.

We investigated the organisation of working memory processes by examining how a secondary memory task interferes with the accuracy of memory-guided saccades. A target was flashed at a random location, followed by a Kanji character. Subjects had to remember the location of the target and the Kanji character, and then they had to make a saccade towards the remembered target location. A second Kanji character was displayed and the subject had to decide if it was same or different. The performance of seven non-Kanji reader's were compared with six fluent Kanji readers in the task. Memorisation of Kanji characters was found to interfere with the accuracy of memory-guided saccades made by non-Kanji, but not by Kanji readers. These findings directly contradict accounts of working memory function which propose that spatial and visual object memory are functionally discrete.