Abstract: Current recommendations for screening for monoclonal gammopathies include serum protein electrophoresis (PEL), imunofixation electrophoresis (IFE), and free light chain (FLC) ratios to identify or rule out an M-protein. The aim of this study was to examine the feasibility of an assay based on immunoenrichment and MALDI-TOF-MS (MASS-SCREEN) to qualitatively screen for M-proteins. METHODS Serum from 556 patients previously screened for M-proteins by PEL and IFE were immunopurified using a κ/λ-specific nanobody bead mixture. Following purification, light chains (LC) were released from their heavy chains by reduction. MALDI-TOF analysis was performed and the mass-to-charge LC distributions were visually examined for the presence of an M-protein by both unblinded and blinded analysts. RESULTS In unblinded analysis, MASS-SCREEN detected 100% of the PEL-positive samples with an analytical sensitivity and specificity of 96% and 81% using IFE positivity as the standard. In a blinded analysis using 6 different laboratory personnel, consensus was reached in 92% of the samples. Overall analytical sensitivity and specificity were reduced to 92% and 80%, respectively. FLC ratios were found to be abnormal in 28% of MASS-SCREEN–negative samples, suggesting FLC measurements need to be considered in screening. CONCLUSIONS MASS-SCREEN could replace PEL in a panel that would include FLC measurements. Further studies and method development should be performed to validate the clinical sensitivity and specificity and to determine if this panel will suffice as a general screen for monoclonal proteins.

Abstract: The cost to healthcare of wasted medicines has been estimated at around £300million per annum (1). In response to this figure and efforts to increase medicines management performance across pharmacy and patient outcomes, the practice of ‘medicines optimisation’ has developed into a key aspect of patient care. In particular, concerns exist around whether patients are deriving the optimum benefit from their medications and the extent to which adherence ‘drops off’ at varying intervals after prescription and collection. In order to tackle medicines adherence and waste, a multi-disciplinary approach must be applied to ensure patients who are prescribed a new medicine take it as intended, experience no problems and receive as much information as they feel they need from healthcare professionals (HCP’s). Adapting Cognitive Behavioural Therapy (CBT)-based techniques to medicines-related consultations has proven effective in supporting medicines adherence in previous studies (2). Collectively, findings demonstrate scope for improving the way HCP’s communicate with patients around starting a new medication and monitoring ongoing use. Aim The study aim was to adapt an existing, Royal College of General Practitioners accredited ’10-minute CBT’ training package to be suitable for wider use by a range of healthcare professionals (HCP’s) (i.e. Practice Nurses, Community Pharmacists, Hospital Pharmacists and General Practitioners). Methods The research design adopted a repeated-measures, pre/ post questionnaire study that gathered data on HCP knowledge around the use of CBT-based techniques in consultations at the start and end of the training intervention. Two training days were attended by HCP’s that took place three weeks apart. The degree of satisfaction with the training intervention was assessed, along with a formulation exercise that was completed on a hypothetical patient case study pre- and post-training. Results Training of healthcare professionals took place at the Oxford Science Park and 105 NHS staff members participated. Feedback questionnaires were received by 96 HCP’s and 46 HCP’s provided additional follow-up questionnaires at 6-months, demonstrating favourable results regarding intervention content and delivery that were consistent with a prior feasibility study. Paired samples t-tests were performed on each formulation exercise rating scale domain and for total scores. There was a highly statistically significant increase in scores for all domains including total pre- and post-training scores as measured by the Formulation Rating Scale. Intra-class Correlation Coefficient for mean FRS ratings was 0.99 (p=.000) and there was no statistically significant change in any score when attendees repeated the skills assessment at 6 months, indicating once learning had been incorporated into practice, there was no recognisable training degradation over the 6-month period. See Table 1. Conclusion The training intervention was rated favourably by attendees and was reported by participants as providing a safe environment from which to increase knowledge of CBT-based techniques, practice implementation of formulation skills and access additional peer support to help integrate learning into medicines-related consultations. The study also demonstrates this group of HCP’s were able to integrate CBT-based techniques into hypothetical medicines-related scenarios and that learning was retained over a six-month period following training intervention. References 1. York Health Economics Consortium and the School of Pharmacy, University of London. Evaluation of the Scale, Causes and Costs of Waste Medicines. 2010. http://php.york.ac.uk/inst/yhec/web/news/documents/Evaluation_of_NHS_Medicines_Waste_Nov_2010.pdf 2. Easthall C, Song F, Bhattacharya D. A meta-analysis of cognitive-based behaviour change techniques as interventions to improve medication Adherence. BMJ Open 2013;3:e002749.

Abstract: Information is needed to monitor progress toward a level of population immunity to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) sufficient to disrupt viral transmission. We estimated the percentage of the US population with presumed immunity to SARS-CoV-2 due to vaccination, natural infection, or both as of August 26, 2021. Methods Publicly available data as of August 26, 2021, from the Centers for Disease Control and Prevention were used to calculate presumed population immunity by state. Seroprevalence data were used to estimate the percentage of the population previously infected with SARS-CoV-2, with adjustments for underreporting. Vaccination coverage data for both fully and partially vaccinated persons were used to calculate presumed immunity from vaccination. Finally, we estimated the percentage of the total population in each state with presumed immunity to SARS-CoV-2, with a sensitivity analysis to account for waning immunity, and compared these estimates with a range of population immunity thresholds. Results In our main analysis, which was the most optimistic scenario, presumed population immunity varied among states (43.1% to 70.6%), with 19 states with ≤60% of their population having been infected or vaccinated. Four states had presumed immunity greater than thresholds estimated to be sufficient to disrupt transmission of less infectious variants (67%), and none were greater than the threshold estimated for more infectious variants (≥78%). Conclusions The United States remains a distance below the threshold sufficient to disrupt viral transmission, with some states remarkably low. As more infectious variants emerge, it is critical that vaccination efforts intensify across all states and ages for which the vaccines are approved.

Abstract: A mass‐balance budget of N cycling was developed for an intensive agricultural area in west‐central Minnesota to better understand NO − 3 contamination of ground water in the Otter Tail outwash aquifer. Fertilizer, biological fixation, atmospheric deposition, and animal feed were the N sources, and crop harvests, animal product exports, volatilization from fertilizer and manure, and denitrification were the N sinks in the model. Excess N, calculated as the difference between the sources and sinks, was assumed to leach to ground water as NO − 3 . The budget was developed using ground water data collected throughout the 212‐km 2 study area. Denitrification was estimated by adjusting its value so the predicted and measured concentrations of NO 3 in ground water agreed. Although biological fixation was the largest single N source, most was removed when crops were harvested, indicating that inorganic fertilizer was the primary source of N reaching the water table. It was estimated that denitrification removed almost half of the excess NO − 3 that leached below the root zone. Even after accounting for denitrification losses, however, it was concluded that the ground water system was receiving approximately three times as much N as would be expected under background conditions.

Abstract: ABSTRACT: The environmental setting of the Red River of the North basin within the United States is diverse in ways that could significantly control the areal distribution and flow of water and, therefore, the distribution and concentration of constituents that affect water quality. Continental glaciers shaped a landscape of very flat lake plains near the center of the basin, and gently rolling uplands, lakes, and wetlands along the basin margins. The fertile, black, fine‐grained soils and landscape are conducive to agriculture. Productive cropland covers 66 percent of the land area. The principal crops are wheat, barley, soybeans, sunflowers, corn, and hay. Pasture, forests, open water, and wetlands comprise most of the remaining land area. About one‐third of the 1990 population (511,000) lives in the cities of Fargo and Grand Forks, North Dakota and Moorhead, Minnesota. The climate of the Red River of the North basin is continental and ranges from dry subhumid in the western part of the basin to subhumid in the eastern part. From its origin, the Red River of the North meanders northward for 394 miles to the Canadian border, a path that is nearly double the straight‐line distance. The Red River of the North normally receives over 75 percent of its annual flow from the eastern tributaries as a result of regional patterns of precipitation, evapotranspiration, soils, and topography. Most runoff occurs in spring and early summer as a result of rains falling on melting snow or heavy rains falling on saturated soils. Lakes, prairie potholes, and wetlands are abundant in most physiographic areas outside of the Red River Valley Lake Plain. Dams, drainage ditches, and wetlands alter the residence time of water, thereby affecting the amount of sediment, biota, and dissolved constituents carried by the water. Ground water available to wells, streams, and springs primarily comes from sand and gravel aquifers near land surface or buried within 100 to 300 feet of glacial drift that mantles the entire Red River of the North basin. Water moves through the system of bedrock and glacial‐drift aquifers in a regional flow system generally toward the Red River of the North and in complex local flow systems controlled by local topography. Many of the bedrock and glacial‐drift aquifers are hydraulically connected to streams in the region. The total water use in 1990, about 196 million gallons per day, was mostly for public supply and irrigation. Slightly more than one half of the water used comes from ground‐water sources compared to surface‐water sources. Most municipalities obtain their water from ground‐water sources. However, the largest cities (Fargo, Grand Forks and Moorhead) obtain most of their water from the Red River of the North. The types and relative amounts of various habitats change among the five primary ecological regions within the Red River of the North basin. Headwater tributaries are more diverse and tend to be similar to middle‐reach tributaries in character rather than the lower reaches of these tributaries for the Red River of the North. Concentrations of dissolved chemical constituents in surface waters are normally low during spring runoff and after thunderstorms. The Red River of the North generally has a dissolved‐solids concentration less than 600 milligrams per liter with mean values ranging from 347 milligrams per liter near the headwaters to 406 milligrams per liter at the Canadian border near Emerson, Manitoba. Calcium and magnesium are the principal cations and bicarbonate is the principal anion along most of the reach of the Red River of the North. Dissolved‐solids concentrations generally are lower in the eastern tributaries than in the tributaries draining the western part of the basin. At times of low flow, when water in streams is largely from ground‐water seepage, the water quality more reflects the chemistry of the glacial‐drift aquifer system. Ground water in the surficial aquifers commonly is a calcium bicarbonate type with dissolved‐solids concentration generally between 300 and 700 milligrams per liter. As the ground water moves down gradient, dissolved‐solids concentration increases, and magnesium and sulfate are predominant ions. Water in sedimentary bedrock aquifers is predominantly sodium and chloride and is characterized by dissolved‐solids concentrations in excess of 1,000 milligrams per liter. Sediment erosion by wind and water can be increased by cultivation practices and by livestock that trample streambanks. Nitrate‐nitrogen concentrations also can increase locally in surficial aquifers beneath cropland that is fertilized, particularly where irrigated. Nitrogen and phosphorous in surface runoff from cropland fertilizers and nitrogen from manure can contribute nutrients to lakes, reservoirs, and streams. Some of the more persistent pesticides, such as atrazine, have been detected in the Red River of the North. Few data are available to conclusively define the presence or absence of pesticides and their break‐down products in Red River of the North basin aquifers or streams. Urban runoff and treated effluent from municipalities are discharged into streams. These point discharges contain some quantity of organic compounds from storm runoff, turf‐applied pesticides, and trace metals. The largest releases of treated‐municipal wastes are from the population centers along the Red River of the North and its larger tributaries. Sugar‐beet refining, potato processing, poultry and meat packing, and milk, cheese, and cream processing are among the major food processes from which treated wastes are released to streams, mostly in or near the Red River of the North.