Organic conversion strategies for stockless farming systems

This report was presented at the UK Organic Research 2002 Conference. The identification of appropriate stockless organic conversion strategies will help farmers and growers in their decision to convert to organic production. The current practice of a two-year red clover/ryegrass ley conversion relies on subsidies to be economically viable. This standard conversion and six alternatives were tested on a sandy loam soil entering organic conversion. A test crop of winter wheat will be grown across the entire experimental area in the first fully organic year (2001/2002). Strategies containing a legume ley phase returned the greatest amount of nitrogen to the soil. At the end of the second year, pre-cultivation, there were no differences in soil mineral nitrogen between strategies. Gross margins were greater from those strategies with cash cropping than those without, in spite of the generally depressed yields. Preliminary analysis suggests that growing red clover for seed in year 1 followed by a red clover ley in year 2 could be the most profitable option

Characteristics of US Medicare Beneficiaries with Chronic Cough vs. Non-Chronic Cough: 2011–2018

Background: Chronic cough (CC), characterized as a cough lasting >8 weeks, is a common multi-factorial syndrome in the community, especially in older adults. Methods: Using a pre-existing algorithm to identify patients with CC within the 2011-2018 Medicare beneficiaries, we examined trends in gabapentinoid use through repeated cross-sectional analyses and identified distinct utilization trajectories using group-based trajectory modeling (GBTM) in a retrospective cohort study. Individuals without CC but with any respiratory conditions related to cough served as a comparator group. Results: Among patients with CC, gabapentinoid use increased from 18.6% in 2011 to 24.1% in 2018 (p = 0.002), with a similar upward trend observed in the non-CC cohort but with overall lower usage (14.7% to 18.4%; p < 0.001). Patients with CC had significantly higher burdens of respiratory and non-respiratory comorbidities, as well as greater healthcare service and medication use compared to the non-CC cohort. The GBTM analyses identified three distinct gabapentinoid utilization trajectories for CC and non-CC patients: no use (77.3% vs. 84.5%), low use (13.9% vs. 10.3%), and high use (8.8% vs. 5.2%). Conclusions: Future studies are needed to evaluate the safety and effectiveness of gabapentinoid use in patients with refractory or unexplained CC in real-world settings

Paroxetine in human milk

Aims The primary aims of the study were to estimate the exposure of infants to paroxetine via breast milk and to determine the maternal milk:plasma ratio (M/P) of paroxetine. Secondary aims were to compare single point and area under the curve (AUC) estimates of M/P, to assess variability of M/P in fore and hind milk, and to compare the observed M/P with that predicted by a model. Methods Two studies were performed. In one study, six nursing mothers who were being treated with paroxetine were studied over a 24 h dose interval at steady-state. The total amount of paroxetine in the milk was measured, which represented the 'dose' to the infant. The M/P AUC was calculated and compared with a predicted value. In the second study, four nursing mothers who were being treated with paroxetine, were studied at steady-state, around a normal infant feeding time. A single plasma sample and a prefeed milk sample were taken approximately 3 h after the morning dose of paroxetine, and a postfeed milk sample taken around 1 h later. The dose received by the infant was estimated from the average milk concentrations of the pre and postfeed samples using standard assumptions, and M/P calculated directly. Plasma concentrations of paroxetine were measured in 8 of the 10 infants in the two studies. Results The mean dose of paroxetine received by the infants in the first study was 1.13% (range 0.5-1.7) of the weight adjusted maternal dose. The mean M/P AUC was 0.39 (range 0.32-0.51). The predicted M/P was 0.22. The mean dose of paroxetine received by the infants in the second study was 1.25% (range 0.38-2.24) of the weight adjusted maternal dose. The mean M/P was 0.96 (range 0.31-3.33) and did not differ between fore and hind milk. The drug was not detected in the plasma of seven of the infants studied and was detected but not quantifiable (<4 mg l −1 ) in one infant. No adverse effects were observed in any of the infants. Conclusions Measured M/P and estimated infant dose were similar in the two studies, although the range was wider for the single point study. Paroxetine can be considered 'safe' during breast feeding because the dose transferred to the infant is well below the recommended safety limit of 10% of the weight adjusted maternal dose, concentrations in the infants were generally undetectable, and no adverse effects were reported

Trends in the Management of Headache Disorders in US Emergency Departments: Analysis of 2007–2018 National Hospital Ambulatory Medical Care Survey Data

We examined trends in management of headache disorders in United States (US) emergency department (ED) visits. We conducted a cross-sectional study using 2007–2018 National Hospital Ambulatory Medical Care Survey data. We included adult patient visits (≥18 years) with a primary ED discharge diagnosis of headache. We classified headache medications by pharmacological group: opioids, butalbital, ergot alkaloids/triptans, acetaminophen/nonsteroidal anti-inflammatory drugs (NSAIDs), antiemetics, diphenhydramine, corticosteroids, and intravenous fluids. To obtain reliable estimates, we aggregated data into three time periods: 2007–2010, 2011–2014, and 2015–2018. Using multivariable logistic regression, we examined medication, neuroimaging, and outpatient referral trends, separately. Among headache-related ED visits, opioid use decreased from 54.1% in 2007–2010 to 28.3% in 2015–2018 (Ptrend < 0.001). There were statistically significant increasing trends in acetaminophen/NSAIDs, diphenhydramine, and corticosteroids use (all Ptrend < 0.001). Changes in butalbital (6.4%), ergot alkaloid/triptan (4.7%), antiemetic (59.2% in 2015–2018), and neuroimaging (37.3%) use over time were insignificant. Headache-related ED visits with outpatient referral for follow-up increased slightly from 73.3% in 2007–2010 to 79.7% in 2015–2018 (Ptrend = 0.02). Reflecting evidence-based guideline recommendations for headache management, opioid use substantially decreased from 2007 to 2018 among US headache-related ED visits. Future studies are warranted to identify strategies to promote evidence-based treatment for headaches (e.g., sumatriptan, dexamethasone) and appropriate outpatient referral and reduce unnecessary neuroimaging orders in EDs

Environmental and farming practice controls of productivity of Cyrtosperma merkusii (giant swamp taro), an underutilised wetland and potential paludiculture crop

Growing recognition of the potential vulnerabilities of major crop systems has spurred a growing interest in the potential of alternative crops which may be resilient to climate change and also help mitigate its effects. In Indonesia, such issues are particularly pertinent given that country's particular vulnerability to climate change impacts high dependence on agricultural livelihoods and varied topographies and growing conditions. Cyrtosperma merkusii (giant swamp taro) is a wetland plant which has historically formed part of food systems in the eastern Pacific. The plant has the potential to be cultivated as a source of starch on marginal coastal land and on peatlands with high water tables. The aim of this paper was therefore to determine site conditions that promote growth of C. merkusii and the macro and micronutrient status of the corms. Naturally, the size of the plants varied substantially among sites, with a neutral pH, and low redox and conductivity being strong edaphic predictors of corm size. Despite substantial differences in the soil properties of the different study sites, there were no significant differences in the macro and micronutrient content of the corms. Field trials showed that although the plants grew under dry land conditions, the plants grew bigger and yielded corms with greater concentrations of Fe, Mn and K under waterlogged conditions, indicating that a high-water table is the best cultivation environment for C. merkusii. The nutrient content of the corms suggests that, although primarily a starch crop, C. merkusii could also increase the intake of Fe in populations where Fe deficiency is pervasive. We conclude that the wetland plant C. merkusii has considerable potential as a paludiculture crop in low-lying areas of SE Asia as it was tolerant of a wide range of soil conditions and performed well when cultivated under waterlogged conditions without additional fertilisation

Evaluation of Cough Medication Use Patterns in Ambulatory Care Settings in the United States: 2003–2018

Using 2003–2018 National Ambulatory Medical Care Survey data for office-based visits and 2003–2018 National Hospital Ambulatory Medical Care Survey data for emergency department (ED) visits, we conducted cross-sectional analyses to examine cough medication (CM) use trends in the United States (US) ambulatory care settings. We included adult (≥18 years) patient visits with respiratory-infection-related or non-infection-related cough as reason-for-visit or diagnosis without malignant cancer or benign respiratory tumor diagnoses. Using multivariable logistic regressions, we examined opioid antitussive, benzonatate, dextromethorphan-containing antitussive, and gabapentinoid use trends. From 2003–2005 to 2015–2018, opioid antitussive use decreased in office-based visits (8.8% to 6.4%, Ptrend = 0.03) but remained stable in ED visits (6.3% to 5.9%, Ptrend = 0.99). In both settings, hydrocodone-containing antitussive use declined over 50%. Benzonatate use more than tripled (office-based:1.6% to 4.8%; ED:1.5% to 8.0%; both Ptrend < 0.001). Dextromethorphan-containing antitussive use increased in ED visits (1.8% to 2.6%, Ptrend = 0.003) but stayed unchanged in office-based visits (3.8% to 2.7%; Ptrend = 0.60). Gabapentinoid use doubled in office-based visits (1.1% in 2006–2008 to 2.4% in 2015–2018, Ptrend < 0.001) but was negligible in ED visits. In US office-based and ED ambulatory care settings, hydrocodone-containing antitussive use substantially declined from 2003 to 2018, while benzonatate use more than tripled, and dextromethorphan-containing antitussive and gabapentinoid use remained low (<3%)

Patterns of Cough Medication Prescribing among Patients with Chronic Cough in Florida: 2012–2021

Among patients with chronic cough (CC) in the 2012–2021 statewide OneFlorida Clinical Research Consortium database, we examined trends in cough medication (CM) prescribing prevalence over time in repeated cross-sectional analyses and identified distinct CM utilization trajectories using group-based trajectory modeling (GBTM) in a retrospective cohort study. Among eligible adults (≥18 years) without cancer/benign respiratory tumor diagnoses, we identified CC patients and non-CC patients with any cough-related diagnosis. In the GBTM analysis, we calculated the number of monthly prescriptions for any CMs (excluding gabapentinoids) during the 12 months from the first qualifying cough event to identify distinct utilization trajectories. From 2012 to 2021, benzonatate (9.6% to 26.1%), dextromethorphan (5.2% to 8.6%), and gabapentinoid (5.3% to 14.4%) use increased among CC patients, while opioid antitussive use increased from 2012 to 2015 and decreased thereafter (8.4% in 2012, 14.7% in 2015, 6.7% in 2021; all p < 0.001). Of 15,566 CC patients and 655,250 non-CC patients identified in the GBTM analysis, CC patients had substantial burdens of respiratory/non-respiratory comorbidities and healthcare service and concomitant medication use compared to non-CC patients. Among CC patients, GBTM identified three distinct CM utilization trajectories: (1) no CM use (n = 11,222; 72.1%); (2) declining CM use (n = 4105; 26.4%); and (3) chronic CM use (n = 239; 1.5%). CC patients in Florida had limited CM use with increasing trends in use of benzonatate, dextromethorphan, and gabapentinoids and a decreasing trend in opioid antitussive use. CC patients, particularly with chronic prescription CM use, experienced substantial disease burden

Home use of a bihormonal bionic pancreas versus insulin pump therapy in adults with type 1 diabetes: a multicentre randomised crossover trial

The safety and effectiveness of a continuous, day-and-night automated glycaemic control system using insulin and glucagon has not been shown in a free-living, home-use setting. We aimed to assess whether bihormonal bionic pancreas initialised only with body mass can safely reduce mean glycaemia and hypoglycaemia in adults with type 1 diabetes who were living at home and participating in their normal daily routines without restrictions on diet or physical activity

New genetic loci implicated in fasting glucose homeostasis and their impact on type 2 diabetes risk.

Levels of circulating glucose are tightly regulated. To identify new loci influencing glycemic traits, we performed meta-analyses of 21 genome-wide association studies informative for fasting glucose, fasting insulin and indices of beta-cell function (HOMA-B) and insulin resistance (HOMA-IR) in up to 46,186 nondiabetic participants. Follow-up of 25 loci in up to 76,558 additional subjects identified 16 loci associated with fasting glucose and HOMA-B and two loci associated with fasting insulin and HOMA-IR. These include nine loci newly associated with fasting glucose (in or near ADCY5, MADD, ADRA2A, CRY2, FADS1, GLIS3, SLC2A2, PROX1 and C2CD4B) and one influencing fasting insulin and HOMA-IR (near IGF1). We also demonstrated association of ADCY5, PROX1, GCK, GCKR and DGKB-TMEM195 with type 2 diabetes. Within these loci, likely biological candidate genes influence signal transduction, cell proliferation, development, glucose-sensing and circadian regulation. Our results demonstrate that genetic studies of glycemic traits can identify type 2 diabetes risk loci, as well as loci containing gene variants that are associated with a modest elevation in glucose levels but are not associated with overt diabetes

Highly Efficient Amplification of Chronic Wasting Disease Agent by Protein Misfolding Cyclic Amplification with Beads (PMCAb)

Protein misfolding cyclic amplification (PMCA) has emerged as an important technique for detecting low levels of pathogenic prion protein in biological samples. The method exploits the ability of the pathogenic prion protein to convert the normal prion protein to a proteinase K-resistant conformation. Inclusion of Teflon® beads in the PMCA reaction (PMCAb) has been previously shown to increase the sensitivity and robustness of detection for the 263 K and SSLOW strains of hamster-adapted prions. Here, we demonstrate that PMCAb with saponin dramatically increases the sensitivity of detection for chronic wasting disease (CWD) agent without compromising the specificity of the assay (i.e., no false positive results). Addition of Teflon® beads increased the robustness of the PMCA reaction, resulting in a decrease in the variability of PMCA results. Three rounds of serial PMCAb allowed detection of CWD agent from a 6.7×10−13 dilution of 10% brain homogenate (1.3 fg of source brain). Titration of the same brain homogenate in transgenic mice expressing cervid prion protein (Tg(CerPrP)1536+/− mice) allowed detection of CWD agent from the 10−6 dilution of 10% brain homogenate. PMCAb is, thus, more sensitive than bioassay in transgenic mice by a factor exceeding 105. Additionally, we are able to amplify CWD agent from brain tissue and lymph nodes of CWD-positive white-tailed deer having Prnp alleles associated with reduced disease susceptibility