Early introductions and transmission of SARS-CoV-2 variant B.1.1.7 in the United States.

The emergence and spread of SARS-CoV-2 lineage B.1.1.7, first detected in the United Kingdom, has become a global public health concern because of its increased transmissibility. Over 2,500 COVID-19 cases associated with this variant have been detected in the United States (US) since December 2020, but the extent of establishment is relatively unknown. Using travel, genomic, and diagnostic data, we highlight that the primary ports of entry for B.1.1.7 in the US were in New York, California, and Florida. Furthermore, we found evidence for many independent B.1.1.7 establishments starting in early December 2020, followed by interstate spread by the end of the month. Finally, we project that B.1.1.7 will be the dominant lineage in many states by mid- to late March. Thus, genomic surveillance for B.1.1.7 and other variants urgently needs to be enhanced to better inform the public health response.

Multiplex qPCR discriminates variants of concern to enhance global surveillance of SARS-CoV-2.

With the emergence of Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) variants that may increase transmissibility and/or cause escape from immune responses, there is an urgent need for the targeted surveillance of circulating lineages. It was found that the B.1.1.7 (also 501Y.V1) variant, first detected in the United Kingdom, could be serendipitously detected by the Thermo Fisher TaqPath COVID-19 PCR assay because a key deletion in these viruses, spike Δ69-70, would cause a "spike gene target failure" (SGTF) result. However, a SGTF result is not definitive for B.1.1.7, and this assay cannot detect other variants of concern (VOC) that lack spike Δ69-70, such as B.1.351 (also 501Y.V2), detected in South Africa, and P.1 (also 501Y.V3), recently detected in Brazil. We identified a deletion in the ORF1a gene (ORF1a Δ3675-3677) in all 3 variants, which has not yet been widely detected in other SARS-CoV-2 lineages. Using ORF1a Δ3675-3677 as the primary target and spike Δ69-70 to differentiate, we designed and validated an open-source PCR assay to detect SARS-CoV-2 VOC. Our assay can be rapidly deployed in laboratories around the world to enhance surveillance for the local emergence and spread of B.1.1.7, B.1.351, and P.1.

A practical training program for fluid milk defect judging should focus on initial training of panelists.

The sensory quality of fluid milk is of great importance to processors and consumers. Defects in the expected odor, flavor, or body of the product can affect consumer attitudes toward the product and, ultimately, willingness to purchase the product. Although many methods of sensory evaluation have been developed, defect judging is one particular method that has been used for decades in the dairy industry for evaluating fluid milk. Defect judging is a technique whereby panelists are trained to recognize and rate a standard set of fluid milk defects that originate from various sources (e.g., microbial spoilage). This technique is primarily used in processing facilities where identification of sensory defects can alert personnel to potential quality control issues in raw material quality, processing, or good manufacturing practices. In 2014-2016, a preliminary study of defective milk judging screening and training was conducted by the Milk Quality Improvement Program at Cornell University (Ithaca, NY). The study, which included 37 staff and students from the Cornell community, used prescreenings for common odors and basic tastes, followed by uniform training to select, initially train, and retrain defect judges of unflavored high temperature, short time fluid milk. Significant improvements were seen in correct identification of defect attributes following initial training for all defect attributes, with the exception of fruity/fermented. However, following retraining, significant improvements were observed in only 2 defect attributes: cooked and milk carton. These results demonstrate that initial training is important for panelists to correctly identify fluid milk defect attributes, but that subsequent retraining should be tailored toward specific attributes. This study provides a resource for dairy industry stakeholders to use to develop relevant and efficient training methods for fluid milk defect judging panels.

Synthesis of Large Mesoporous-Macroporous and High Pore Volume, Mixed Crystallographic Phase Manganese Oxide, Mn2O3/Mn3O4 Sponge.

The controlled synthesis of mixed crystallographic phase Mn2O3/Mn3O4 sponge material by varying heating rates and isothermal segments provides valuable information about the morphological and physical properties of the obtained sample. The well-characterized Mn2O3/Mn3O4 sponge and applicability of difference in reactivity of H2 and CO2 desorbed during the synthesis provide new developments in the synthesis of metal oxide materials with unique morphological and surface properties. We report the preparation of a Mn2O3/Mn3O4 sponge using a metal nitrate salt, water, and Dextran, a biopolymer consisting of glucose monomers. The Mn2O3/Mn3O4 sponge prepared at 1 °C·min-1 heating rate to 500 °C and held isothermally for 1 h consisted of large mesopores-macropores (25.5 nm, pore diameter) and a pore volume of 0.413 mL/g. Furthermore, the prepared Mn2O3/Mn3O4 and 5 mol %-Fe-Mn2O3/Mn3O4 sponges provide potential avenues in the development of solid-state catalyst materials for alcohol and amine oxidation reactions.

Influence of raw milk quality on processed dairy products: How do raw milk quality test results relate to product quality and yield?

This article provides an overview of the influence of raw milk quality on the quality of processed dairy products and offers a perspective on the merits of investing in quality. Dairy farmers are frequently offered monetary premium incentives to provide high-quality milk to processors. These incentives are most often based on raw milk somatic cell and bacteria count levels well below the regulatory public health-based limits. Justification for these incentive payments can be based on improved processed product quality and manufacturing efficiencies that provide the processor with a return on their investment for high-quality raw milk. In some cases, this return on investment is difficult to measure. Raw milks with high levels of somatic cells and bacteria are associated with increased enzyme activity that can result in product defects. Use of raw milk with somatic cell counts >100,000cells/mL has been shown to reduce cheese yields, and higher levels, generally >400,000 cells/mL, have been associated with textural and flavor defects in cheese and other products. Although most research indicates that fairly high total bacteria counts (>1,000,000 cfu/mL) in raw milk are needed to cause defects in most processed dairy products, receiving high-quality milk from the farm allows some flexibility for handling raw milk, which can increase efficiencies and reduce the risk of raw milk reaching bacterial levels of concern. Monitoring total bacterial numbers in regard to raw milk quality is imperative, but determining levels of specific types of bacteria present has gained increasing importance. For example, spores of certain spore-forming bacteria present in raw milk at very low levels (e.g., <1/mL) can survive pasteurization and grow in milk and cheese products to levels that result in defects. With the exception of meeting product specifications often required for milk powders, testing for specific spore-forming groups is currently not used in quality incentive programs in the United States but is used in other countries (e.g., the Netherlands).

Exposure of fluid milk to LED light negatively affects consumer perception and alters underlying sensory properties.

Fluid milk consumption per capita in the United States has been steadily declining since the 1940s. Many factors have contributed to this decline, including the increasing consumption of carbonated beverages and bottled water. To meet the challenge of stemming the decline in consumption of fluid milk, the dairy industry must take a systematic approach to identifying and correcting for factors that negatively affect consumers' perception of fluid milk quality. To that end, samples of fluid milk were evaluated to identify factors, with a particular focus on light-emitting diode (LED) light exposure, which negatively affect the perceived sensory quality of milk, and to quantify their relative effect on the consumer's experience. Fluid milk samples were sourced from 3 processing facilities with varying microbial postprocessing contamination patterns based on historical testing. The effect of fat content, light exposure, age, and microbiological content were assayed across 23 samples of fluid milk, via consumer, descriptive sensory, and instrumental analyses. Most notably, light exposure resulted in a broad negative reaction from consumers, more so than samples with microbiological contamination exceeding 20,000 cfu/mL on days approaching code. The predominant implication of the study is that a component of paramount importance in ensuring the success of the dairy industry would be to protect fluid milk from all sources of light exposure, from processing plant to consumer.

The viability of photocatalysis for air purification.

Photocatalytic oxidation (PCO) air purification technology is reviewed based on the decades of research conducted by the United Technologies Research Center (UTRC) and their external colleagues. UTRC conducted basic research on the reaction rates of various volatile organic compounds (VOCs). The knowledge gained allowed validation of 1D and 3D prototype reactor models that guided further purifier development. Colleagues worldwide validated purifier prototypes in simulated realistic indoor environments. Prototype products were deployed in office environments both in the United States and France. As a result of these validation studies, it was discovered that both catalyst lifetime and byproduct formation are barriers to implementing this technology. Research is ongoing at the University of Connecticut that is applicable to extending catalyst lifetime, increasing catalyst efficiency and extending activation wavelength from the ultraviolet to the visible wavelengths. It is critical that catalyst lifetime is extended to realize cost effective implementation of PCO air purification.

Electrically conducting polymers as templating interfaces for fabrication of copper nanotubes.

Submicrometer tubes have been fabricated by a polymer-based template approach using electroless deposition. The copper was deposited on polystyrene fibers functionalized with an interfacial electrically conducting polyaniline thin film layer. Thermal degradation of the functionalized fiber templates resulted in copper tubes of diameter 1600 ± 50 nm with wall thicknesses ranging between 100 and 200 nm. The morphology and elemental analysis of copper coaxial fibers was analyzed using SEM and EDS. Electrical properties were analyzed using FTIR and PXRD was used to study crystal structure of copper nanotubes.

A national survey of the radiotherapy dosimetrist workforce in the UK.

OBJECTIVES: To undertake a national survey of the Radiotherapy Dosimetrist workforce within the UK; examining different attributes and experiences, comparing results with published evidence within the literature. METHODS: A national, anonymised survey was undertaken between Dec 2020 and end of Feb 2021; employing a mixed-methods approach and blend of closed, open-ended answer choices and free-text comments. Questions included range of training routes and job titles; registration status; job tasks and engagement with Continuing Professional Development (CPD). RESULTS: A total of 223 individuals responded. Nearly half were trained via therapeutic radiography; approximately, a fifth through a clinical technologist/physics routes. Most (70%) had Dosimetrist in their job title. Nearly 70% were statutorily registered, and almost a fifth were in the voluntary register of Clinical Technologists. Most job tasks were in treatment planning - with 57% spending over 70% of their time there. Most notably, 29% were not involved in any CPD scheme. No published evidence showed the same aspects identified here. CONCLUSIONS: Our survey showed a unique profile of the Radiotherapy Dosimetrist workforce in the UK, with a variety of training routes and statutory registration status. Nearly, a third were not engaged in a CPD scheme - adding to the current discussion that perhaps all Dosimetrists should be statutorily registered, for ensuring safe and effective clinical practice. ADVANCES IN KNOWLEDGE: A novel and unique national survey of Dosimetrists working in Radiotherapy in the UK is presented, leading to new insights into current training routes, registration status, job tasks and CPD engagement and needs.

Combining genomic and epidemiological data to compare the transmissibility of SARS-CoV-2 variants Alpha and Iota.

SARS-CoV-2 variants shaped the second year of the COVID-19 pandemic and the discourse around effective control measures. Evaluating the threat posed by a new variant is essential for adapting response efforts when community transmission is detected. In this study, we compare the dynamics of two variants, Alpha and Iota, by integrating genomic surveillance data to estimate the effective reproduction number (Rt) of the variants. We use Connecticut, United States, in which Alpha and Iota co-circulated in 2021. We find that the Rt of these variants were up to 50% larger than that of other variants. We then use phylogeography to show that while both variants were introduced into Connecticut at comparable frequencies, clades that resulted from introductions of Alpha were larger than those resulting from Iota introductions. By monitoring the dynamics of individual variants throughout our study period, we demonstrate the importance of routine surveillance in the response to COVID-19.

PCR assay to enhance global surveillance for SARS-CoV-2 variants of concern.

With the emergence of SARS-CoV-2 variants that may increase transmissibility and/or cause escape from immune responses 1-3 , there is an urgent need for the targeted surveillance of circulating lineages. It was found that the B.1.1.7 (also 501Y.V1) variant first detected in the UK 4,5 could be serendipitously detected by the ThermoFisher TaqPath COVID-19 PCR assay because a key deletion in these viruses, spike Δ69-70, would cause a "spike gene target failure" (SGTF) result. However, a SGTF result is not definitive for B.1.1.7, and this assay cannot detect other variants of concern that lack spike Δ69-70, such as B.1.351 (also 501Y.V2) detected in South Africa 6 and P.1 (also 501Y.V3) recently detected in Brazil 7 . We identified a deletion in the ORF1a gene (ORF1a Δ3675-3677) in all three variants, which has not yet been widely detected in other SARS-CoV-2 lineages. Using ORF1a Δ3675-3677 as the primary target and spike Δ69-70 to differentiate, we designed and validated an open source PCR assay to detect SARS-CoV-2 variants of concern 8 . Our assay can be rapidly deployed in laboratories around the world to enhance surveillance for the local emergence spread of B.1.1.7, B.1.351, and P.1.

Combining genomic and epidemiological data to compare the transmissibility of SARS-CoV-2 lineages.

Emerging SARS-CoV-2 variants have shaped the second year of the COVID-19 pandemic and the public health discourse around effective control measures. Evaluating the public health threat posed by a new variant is essential for appropriately adapting response efforts when community transmission is detected. However, this assessment requires that a true comparison can be made between the new variant and its predecessors because factors other than the virus genotype may influence spread and transmission. In this study, we develop a framework that integrates genomic surveillance data to estimate the relative effective reproduction number (R t ) of co-circulating lineages. We use Connecticut, a state in the northeastern United States in which the SARS-CoV-2 variants B.1.1.7 and B.1.526 co-circulated in early 2021, as a case study for implementing this framework. We find that the R t of B.1.1.7 was 6-10% larger than that of B.1.526 in Connecticut in the midst of a COVID-19 vaccination campaign. To assess the generalizability of this framework, we apply it to genomic surveillance data from New York City and observe the same trend. Finally, we use discrete phylogeography to demonstrate that while both variants were introduced into Connecticut at comparable frequencies, clades that resulted from introductions of B.1.1.7 were larger than those resulting from B.1.526 introductions. Our framework, which uses open-source methods requiring minimal computational resources, may be used to monitor near real-time variant dynamics in a myriad of settings.

Early introductions and community transmission of SARS-CoV-2 variant B.1.1.7 in the United States.

The emergence and spread of SARS-CoV-2 lineage B.1.1.7, first detected in the United Kingdom, has become a global public health concern because of its increased transmissibility. Over 2500 COVID-19 cases associated with this variant have been detected in the US since December 2020, but the extent of establishment is relatively unknown. Using travel, genomic, and diagnostic data, we highlight the primary ports of entry for B.1.1.7 in the US and locations of possible underreporting of B.1.1.7 cases. Furthermore, we found evidence for many independent B.1.1.7 establishments starting in early December 2020, followed by interstate spread by the end of the month. Finally, we project that B.1.1.7 will be the dominant lineage in many states by mid to late March. Thus, genomic surveillance for B.1.1.7 and other variants urgently needs to be enhanced to better inform the public health response.

Investigation of 4-piperidinols as novel H3 antagonists.

Compounds containing a substituted 4-piperidinol core have been found to be potent antagonists of the human H(3) receptor. The compounds exhibited up to a 60-fold preference for inhibiting the human H(3) receptor over the mouse and showed a low binding affinity for the hERG channel.

3-Indolyl sultams as selective CRTh2 antagonists.

CRTh2 (DP(2)) is a prostaglandin D(2) receptor implicated in the recruitment of eosinophils and basophils within the asthmatic lung. Here we report the discovery of a novel series of 3-indolyl sultam antagonists with low nM affinity for CRTh2. These compounds proved to be selective over the other primary prostaglandin D(2) receptor (DP1) as well as the thromboxane A(2) receptor (TP).

Delaware's inclusive trauma system: impact on mortality.

BACKGROUND: The impact of implementing an inclusive state trauma system on injury-related mortality for patients with life-threatening injuries was assessed. METHODS: Using the state trauma registry, trauma patients evaluated in all of Delaware's acute care hospitals from 1998 to 2007 were identified. Patients were categorized by injury severity score (ISS) groups (1-9, 10-15, 16-24, and >24). Each category was analyzed by mortality and interfacility transfer rate to the Level I trauma center for each year. An analysis of the National Trauma Data Bank (NTDB) for these ISS groups and mortality was performed to provide a comparative benchmark. Chi(2) and analysis of variance were used where appropriate (p 24 group. For this group, there was an incremental mortality decrease from 45.7% (1998) to 20.5% (2007) (p 24 group managed at the Level I hospital significantly increased over the same period. CONCLUSION: Since its inception, Delaware's trauma system, in which all acute care hospitals participate, has been associated with an incremental, significant decrease in mortality of the most critically injured patients. This decrease is more substantial than that experienced nationally as depicted within the NTDB. These findings and our evolving experience support the concept and benefits of an "inclusive" trauma system.

Food safety hazards associated with consumption of raw milk.

An increasing number of people are consuming raw unpasteurized milk. Enhanced nutritional qualities, taste, and health benefits have all been advocated as reasons for increased interest in raw milk consumption. However, science-based data to substantiate these claims are limited. People continue to consume raw milk even though numerous epidemiological studies have shown clearly that raw milk can be contaminated by a variety of pathogens, some of which are associated with human illness and disease. Several documented milkborne disease outbreaks occurred from 2000-2008 and were traced back to consumption of raw unpasteurized milk. Numerous people were found to have infections, some were hospitalized, and a few died. In the majority of these outbreaks, the organism associated with the milkborne outbreak was isolated from the implicated product(s) or from subsequent products made at the suspected dairy or source. In contrast, fewer milkborne disease outbreaks were associated with consumption of pasteurized milk during this same time period. Twenty nine states allow the sale of raw milk by some means. Direct purchase, cow-share or leasing programs, and the sale of raw milk as pet food have been used as means for consumers to obtain raw milk. Where raw milk is offered for sale, strategies to reduce risks associated with raw milk and products made from raw milk are needed. Developing uniform regulations including microbial standards for raw milk to be sold for human consumption, labeling of raw milk, improving sanitation during milking, and enhancing and targeting educational efforts are potential approaches to this issue. Development of pre- and postharvest control measures to effectively reduce contamination is critical to the control of pathogens in raw milk. One sure way to prevent raw milk-associated foodborne illness is for consumers to refrain from drinking raw milk and from consuming dairy products manufactured using raw milk.

Two-year to five-year follow-up of femoral defects in femoral revision treated with the link MP modular stem.

Femoral deficiency has been shown to adversely affect the results of revision total hip arthroplasty. Tapered titanium modular stems allow distal fixation of the fluted, conical portion of the implant in the setting of proximal bone loss. One hundred two consecutive hips with proximal bone loss underwent revision femoral reconstruction between 1998 and 2002 at 3 centers using the Link MP modular stem. Forty-three hips had Mallory type 3C femoral deficiency. Ninety-seven hips were observed for an average of 45 months (range, 24-72; median, 36 months). Clinically, mean Harris hip score improved from 36 to 84 (range, 54-99). Radiographically, 93 hips were considered stable, with no circumferential lucencies at the distal fixation surface. Three hips migrated and required revision, along with one periprosthetic fracture. Five other hips had nonprogressive migration of 1 to 2 mm.

Evaluation of functional and binding assays in cells expressing either recombinant or endogenous hERG channel.

INTRODUCTION: The hERG (human ether-a-go-go related gene) potassium channel is required for normal cardiac repolarization, is susceptible to inhibition by a wide variety of compounds, and its blockage can lead to cardiac QT interval prolongation and life threatening arrhythmias. The present report examines the ability of hERG binding and functional assays to identify compounds with potential cardiovascular liabilities at the earliest stages of drug discovery. METHODS: Competitive binding assays were developed using (3)H-dofetilide and membranes from HEK293EBNA cells stably expressing recombinant hERG (HEK293-hERG) and IMR-32 cells expressing hERG endogenously. hERG functional assays were also developed using membrane potential indicator dye and rubidium efflux. The ability of these assays to identify compounds with potential adverse cardiac effects was examined using drugs with known cardiac effects ranging from those with no known adverse effects to drugs that were withdrawn from the market due to increased risk of sudden death associated with Torsades de Points. RESULTS: Binding assays using HEK293-hERG membranes and (3)H-dofetilide were robust (Z'=0.69+/-0.015, mean+/-S.E.M.), highly reproducible (test-retest slope=1.04, r(2)=0.98), and correlated well with IC(50) values obtained by patch clamp (slope=0.98, r(2)=0.89). Binding assays using IMR-32 membranes were less sensitive (Z'=0.4+/-0.03, mean+/-S.E.M., false negative rate=0.4) but still correlated well with patch clamp data (slope=1.06, r(2)=0.83). The hERG membrane potential assay could detect potent hERG inhibitors (defined by hERG patch clamp IC(50)<0.1 muM) using HEK293-hERG cells, but were prone to generate false-negative results with less potent inhibitors (false negative rate=0.5). Finally, the rubidium efflux assay gave highly reproducible results (Z'=0.80+/-0.02, mean+/-S.E.M.) that correlated with patch clamp IC(50) values (slope=0.87, r(2)=0.73). DISCUSSION: The hERG binding and rubidium efflux assays are robust, predictive of patch clamp results, and can be used at the earliest stages of drug discovery.