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Background In May 2021, the B.1.617 variant of SARS-CoV-2 emerged in Ireland, and both Delta and Kappa sub-lineages were initially deemed variants of concern (VOCs) on a precautionary basis. We describe a large outbreak of SARS-CoV-2 B.1.617.1 (Kappa mutation) linked to a private gathering among third level students in Cork, Ireland. Methods Surveillance data were available from the Health Service Executive COVID Care Tracker. The epidemiological sequence of infection for each new case in this outbreak was tracked and whole genome sequencing was requested on all linked cases. Enhanced public health control measures were implemented by the Department of Public Health HSE-South to contain onward spread of VOCs, including retrospective contact tracing, lengthy isolation and quarantine periods for cases and close contacts. Extensive surveillance efforts were used to describe and control onward transmission. Results There were 146 confirmed SARS-CoV-2 cases linked to the outbreak. All sequenced cases (53/146; 36%) confirmed Kappa mutation. The median age was 21 years (range 17–65). The majority (88%) had symptoms of SARS-CoV-2 infection. There were 407 close contacts; the median was 3 per case (range 0–14). There were no known hospitalisations, ICU admissions or deaths. Vaccination data was unavailable, but the outbreak pre-dated routine availability of COVID-19 vaccines among younger adults in Ireland. Conclusion Enhanced public health control measures for new and emerging variants of SARS-CoV-2 may be burdensome for cases and close contacts. The overall public health benefit of enhanced controls may only become apparent when evidence on disease transmissibility and severity becomes more complete.

Percutaneous electrical nerve stimulation: a novel analgesic therapy for diabetic neuropathic pain. M A Hamza , P F White , W F Craig , E S Ghoname , H E Ahmed , T J Proctor , C E Noe , A S Vakharia and N Gajraj Eugene McDermott Center for Pain Management, Department of Anesthesiology and Pain Management, University of Texas Southwestern Medical Center at Dallas, 75235, USA. Abstract OBJECTIVE: To evaluate the use of percutaneous electrical nerve stimulation (PENS) in the management of patients with painful diabetic peripheral neuropathy. RESEARCH DESIGN AND METHODS: A total of 50 adult patients with type 2 diabetes and peripheral neuropathic pain of >6 months duration involving the lower extremities were randomly assigned to receive active PENS (needles with electrical stimulation at an alternating frequency of 15 and 30 Hz) and sham (needles only) treatments for 3 weeks. Each series of treatments was administered for 30 min three times a week according to a standardized protocol. After a 1-week washout period, all patients were subsequently switched to the other modality. A 10-cm visual analog scale (VAS) was used to assess pain, physical activity, and quality of sleep before each session. The changes in VAS scores and daily requirements for oral analgesic medication were determined during each 3-week treatment period. Patients completed the MOS 36-Item Short-Form Health Survey (SF-36), the Beck Depression Inventory (BDI), and the Profile of Mood States (POMS) before and after completion of each treatment modality. At the end of the crossover study, a patient preference questionnaire was used to compare the effectiveness of the two modalities. RESULTS: Compared with the pain VAS scores before active (6.2 +/- 1.0) and sham (6.4 +/- 0.9) treatments, pain scores after treatment were reduced to 2.5 +/- 0.8 and 6.3 +/- 1.1, respectively. With active PENS treatment, the VAS activity and sleep scores were significantly improved from 5.2 +/- 1.0 and 5.8 +/- 1.3 to 7.9 +/- 1.0 and 8.3 +/- 0.7, respectively. The VAS scores for pain, activity, and sleep were unchanged from baseline values after the sham treatments. Patients' daily oral nonopioid analgesic requirements decreased by 49 and 14% after active and sham PENS treatments, respectively. The post-treatment physical and mental components of the SF-36, the BDI, and the POMS all showed a significantly greater improvement with active versus sham treatments. Active PENS treatment improved the neuropathic pain symptoms in all patients. CONCLUSIONS: PENS is a useful nonpharmacological therapeutic modality for treating diabetic neuropathic pain. In addition to decreasing extremity pain, PENS therapy improved physical activity, sense of well-being, and quality of sleep while reducing the need for oral nonopioid analgesic medication.

Previous studies suggest that the positive response of transplanted rice (Oryza sativa L.) to nursery fertiliser application was due to increased seedling vigour or possibly to increased nutrient content. This paper presents results of two glasshouse experiments designed to test the hypothesis that seedling vigour was responsible for the response of transplanted seedlings to nursery treatments. The aim of the present study was to explore the concept of seedling vigour of transplanted rice and to determine what plant attributes conferred vigour on the seedlings. Seedling vigour treatments were established by subjecting seedlings to short-term submergence (0, 1 and 2 days/week) in one experiment and to leaf clipping or root pruning and water stress in another to determine their effect on plant growth after transplanting. Submerging seedlings increased plant height but depressed shoot and root dry matter and root:shoot ratio of the seedling at 28 days after sowing. After transplanting these seedlings, prior submergence depressed shoot dry matter at 40 days. Nursery nutrient application increased plant height, increased root and shoot dry matter, but generally decreased root:shoot ratio. Pruning up to 60% of the roots at transplanting decreased shoot and root dry matter, P concentration in leaves at panicle initiation (PI) and straw dry matter and grain yield at maturity. By contrast, pruning 30% of leaves depressed shoot and root dry matter by 30% at PI, and root dry matter and straw and grain yield by 20% at maturity. The combined effects of leaf clipping and root pruning on shoot, root and straw dry matter were largely additive. It is concluded that the response of rice yield to nursery treatments is largely due to increased seedling vigour and can be effected by a range of nutritional as well as non-nutritional treatments of seedlings that increase seedling dry matter, nutrient content, and nutrient concentration. Impairment of leaf growth and to a lesser extent root growth in the nursery depressed seedling vigour after transplanting. However, rather than increasing stress tolerance, seedling vigour was more beneficial when post transplant growth was not limited by nutrient or water stresses.

Phosphorus cycling in rainfed lowland rice ecosystems is poorly understood. Soil drying and grazing of rice straw during the long dry season, the growth of volunteer pastures during the early wet season, and intermittent loss of soil-water saturation while the rice crop is growing are important distinguishing characteristics of the rainfed lowlands in relation to P cycling. We studied P cycling in an acid sandy rainfed lowland soil that covers about 30% of the rice growing area of Cambodia. Soils with similar properties in comparable rainfed sub- ecosystems occur in Laos and northeast Thailand. We developed a general schema of P pools and fluxes in the crop and soil for rice-based cropping systems in the rainfed lowlands of Cambodia. The schema was derived from a number of field experiments carried out over five consecutive cropping seasons to quantify the residual value of P fertiliser, P mass balances, soil P fractions, the effect on subsequent rice crops of crop residues and volunteer pastures incorporated into the soils, and the dynamics of P turnover in the soil. With a single rice crop yielding 2.5–3 t ha-1, application of 8–10 kg P ha-1 maintained yields and a small positive P balance in the soil. However, the soil P balance was sensitive to the proportion of rice straw returned to the soil. Volunteer pastures growing during the early wet season accumulated significant amounts of P, and increased their P uptake when soils were previously fertilised with P. These pastures recycled 3–10 kg P ha-1 for the succeeding rice crops. While inorganic soil P pools extractable with ion exchange resins and 0.1 M NaOH appeared to be the main source of P absorbed by rice, microbial and organically-bound P pools responded dynamically to variation in soil water regimes of the main wet, dry and early wet seasons. The schema needs to be developed further to incorporate site-specific conditions and management factors that directly or indirectly affect P cycling, especially loss of soil-water saturation during the rice cropping cycle. The paper discusses the application of results for acid sandy soils to other significant rice soils in the rainfed lowlands of southeast Asia.

Raising and sustaining rice yields in the rainfed lowlands requires an understanding of nutrient inputs and outputs. On sandy lowland rice soils, managing phosphorus (P) supply is a key factor in achieving increased yields and sustainable production. Phosphorus inputs, rice yields, and crop P uptake were used to quantify P requirements of rice: together with results on soil P fractions, P balance sheets were constructed over five consecutive cropping seasons on a sandy Plinthustalf near Phnom Penh, Cambodia. Grain yields ranged from 665 to 1557 kg ha(-1) with no added P. Average yields increased significantly with P fertiliser application over five consecutive crops by 117, 139 and 140% when the phosphate fertiliser was applied at 8.25, 16.5 and 33 kg P ha(-1), respectively. Without added P fertiliser, a net loss of 1.2 kg P ha(-1) per crop was estimated with straw return and 2.0 kg P ha(-1) per crop with straw removed from the field, whereas, with added P fertiliser, there was a net P gain in the soil of 5.6 or 9.5 kg ha(-1) per crop when straw was removed and returned to the soil, respectively. After one crop, the addition of P fertiliser significantly (P < 0.01) increased recovery in all soil P fractions. Across five successive crops, repeated application of 16.5 and 33 kg P ha(-1) rates resulted in progressive P accumulation in the soil, especially a labile NaOH-Po pool, but had no effect on yields and P uptake of rice. By contrast, 8.25 kg P ha(-1) per rice crop was generally adequate for grain yields of 2.5-3.0 t ha(-1) and to maintain soil P pools.

A drifter for observing small spatial and temporal scales of motion in the coastal zone is presented. The drifter uses GPS to determine its position, and the Mobitex terrestrial cellular communications system to transmit the position data in near–real time. This configuration allows position data with order meter accuracy to be sampled every few minutes and transmitted inexpensively. Near-real-time transmission of highly accurate position data enables the drifters to be retrieved and redeployed, further increasing economy. Drifter slip measurements indicate that the drifter follows water to within ∼1–2 cm s−1 during light wind periods. Slip values >1 cm s−1 are aligned with the direction of surface wave propagation and are 180° out of phase, so that the drifter “walks” down waves. Nearly 200 drifter tracks collected off the Santa Barbara, California, coast show comparisons with high-frequency (HF) radar observations of near-surface currents that improve by roughly 50% when the average drifter values are computed from more than 25 observations within a 2-km square HF radar bin. The improvement is the result of drifter resolution of subgrid-scale eddies that are included in time–space-averaged HF radar fields. The average eddy kinetic energy on 2-km space and hour time scales is 25 cm2 s−2, when computed for bins with more than 25 drifter observations. Comparisons with trajectories that are computed from HF radar data show mean separation velocities of 5 and 9 cm s−1 in the along- and across-shore directions, respectively. The drifters resolve scales of motion that are not present in HF radar fields, and are thus complementary to HF radar in coastal ocean observing systems.

AbstractBackgroundThe NaV1.8 voltage-gated sodium channel, expressed in peripheral nociceptive neurons, plays a role in transmitting nociceptive signals. The effect of VX-548, an oral, highly selective inhibitor of NaV1.8, on control of acute pain is being studied.MethodsAfter establishing the selectivity of VX-548 for NaV1.8 inhibition in vitro, we conducted two phase 2 trials involving participants with acute pain after abdominoplasty or bunionectomy. In the abdominoplasty trial, participants were randomly assigned in a 1:1:1:1 ratio to receive one of the following over a 48-hour period: a 100-mg oral loading dose of VX-548, followed by a 50-mg maintenance dose every 12 hours (the high-dose group); a 60-mg loading dose of VX-548, followed by a 30-mg maintenance dose every 12 hours (the middle-dose group); hydrocodone bitartrate–acetaminophen (5 mg of hydrocodone bitartrate and 325 mg of acetaminophen every 6 hours); or oral placebo every 6 hours. In the bunionectomy trial, participants were randomly assigned in a 2:2:1:2:2 ratio to receive one of the following over a 48-hour treatment period: oral high-dose VX-548; middle-dose VX-548; low-dose VX-548 (a 20-mg loading dose, followed by a 10-mg maintenance dose every 12 hours); oral hydrocodone bitartrate–acetaminophen (5 mg of hydrocodone bitartrate and 325 mg of acetaminophen every 6 hours); or oral placebo every 6 hours. The primary end point was the time-weighted sum of the pain-intensity difference (SPID) over the 48-hour period (SPID48), a measure derived from the score on the Numeric Pain Rating Scale (range, 0 to 10; higher scores indicate greater pain) at 19 time points after the first dose of VX-548 or placebo. The main analysis compared each dose of VX-548 with placebo.ResultsA total of 303 participants were enrolled in the abdominoplasty trial and 274 in the bunionectomy trial. The least-squares mean difference between the high-dose VX-548 and placebo groups in the time-weighted SPID48 was 37.8 (95% confidence interval [CI], 9.2 to 66.4) after abdominoplasty and 36.8 (95% CI, 4.6 to 69.0) after bunionectomy. In both trials, participants who received lower doses of VX-548 had results similar to those with placebo. Headache and constipation were common adverse events with VX-548.ConclusionsAs compared with placebo, VX-548 at the highest dose, but not at lower doses, reduced acute pain over a period of 48 hours after abdominoplasty or bunionectomy. VX-548 was associated with adverse events that were mild to moderate in severity. (Funded by Vertex Pharmaceuticals; VX21-548-101 and VX21-548-102 ClinicalTrials.gov numbers, NCT04977336 and NCT05034952.)

The use of the intravenous anesthetic etomidate for prolonged sedation has been associated with low levels of plasma cortisol and increased mortality. We measured the cortisol and aldosterone responses to ACTH stimulation in five patients receiving etomidate, and we also studied the direct effects of etomidate on enzymes in the rat steroidogenic pathway. One patient who was receiving a 20-hour infusion of etomidate (1.3 to 1.5 mg per kilogram of body weight per hour) had marked adrenocortical suppression that was still evident four days after etomidate was discontinued. Four surgical patients receiving etomidate during their operations were all found to have adrenal suppression four hours after the operation; mean (±S.D.) increases in cortisol and aldosterone after ACTH stimulation were only 1.8±0.5 μg per deciliter and 0.5±1.1 ng per deciliter, respectively. In rat adrenal cells, etomidate produced a concentration-dependent blockade of the two mitochondrial cytochrome P-450–dependent enzymes, cholesterol-side-chain cleavage enzyme, and 11β-hydroxylase, without evident inhibition of the microsomal enzymes in the glucocorticoid pathway. Physicians should be aware that etomidate Inhibits adrenal steroidogenesis, and they should consider treating selected patients with corticosteroids if etomidate is used. (N Engl J Med 1984; 310:1415–21.) ETOMIDATE is an intravenous sedative-hypnotic that has been used for the induction and maintenance of anesthesia and for prolonged sedation of critically ill patients. The drug is administered by either bolus injection or continuous infusion 1 and is characterized by a rapid onset of action and recovery, 2 excellent cardiovascular stability, 3 and the absence of histamine release. 4 Although only recently available in the United States, etomidate has gained wide acceptance in Furope as an anesthetic for patients with cardiovascular instability 5 and as a sedative for ventilator-dependent patients. 6 Recently, an intensive-care unit in England reported an increased mortality rate 7 associated with low levels . . .

Hyperthermic shock induces the synthesis of a novel protein (P$_{71}$) in many rat tissues in vivo. In incubated rat tissue slices P$_{71}$ is the major protein synthesized even though it is undetectable in the tissues of a normal, unstressed rat. P$_{71}$ is a ``heat shock'' protein, and it may be induced in vivo by stimuli other than hyperthermia. These results indicate that caution must be used in studies of protein synthesis in tissue explants, since the pattern of proteins synthesized by rat tissue slices is characteristic of stressed tissue.

In this paper we review key issues determining nutrient management strategies in irrigated and rainfed lowland riceland and we present two examples of site-specific nutrient management (SSNM) strategies. First, a framework for SSNM in irrigated rice is described, where attaining maximum economical yield is the priority of farmers and SSNM practices must be tailored to the large between-field differences in indigenous nutrient supply. The iterative procedure proposed includes: (1) estimation of the potential indigenous supplies of N (INS), P (IPS), and K (IKS, all in kg ha-1) and diagnosis of other nutritional disorders in year one; (2) estimation of a field- or farm-specific recommendation for fertilizer use based on nutrient interactions and economic yield target; (3) optimization of timing and amount of applied N based on actual plant growth; (4) estimation of the change in INS, IPS and IKS based on the nutrient balance after harvest; and (5) use of the adjusted INS, IPS, and IKS as model inputs for the subsequent rice crop. In a second example we discuss the SSNM strategy that is being developed for rainfed rice farmers in Cambodia. Rainfed lowland rice farmers give priority to reducing risk and their ability to invest in cost-intensive innovative technologies is limited. Farmers' knowledge and experience become vital for the efficient management of nutrients in these environments. In our approach, technologies are generated and tested through research at selected representative sites. Extrapolation and site-specific application of new nutrient management technologies is then supported through a new agronomic soil classification and probabilistic modeling to account for farmer's knowledge and experience. The agronomic soil classification system contains three hierarchical levels and focuses on soil description in the field with relevance to nutrient management. Based on this, preliminary soil-specific fertilizer recommendations for rice have been worked out.