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At least 19 recordsLinked to original sources
PubMed2025

Coordinated regulation of glutathione S-transferases confers metabolic flexibility in multi-insecticide-resistant Frankliniella occidentalis (Pergande).

INTRODUCTION: The evolution of multi-insecticide resistance in insect pests threatens global food security. Although glutathione S-transferases (GSTs) are implicated in detoxification, the coordinated mechanism by which specific gene subfamilies interact to confer broad-spectrum resistance remains inadequately characterized. OBJECTIVE: To dissect the functional allocation and cooperation of GST subfamilies in multi-insecticide-resistant strains of Frankliniella occidentalis. METHODS: We integrated comparative genomics (20 GST genes cloned), transcriptomics (qRT-PCR), RNAi-mediated silencing, molecular docking (AutoDock Vina), and in vitro metabolism assays (UPLC-MS/MS) across susceptible and resistant thrips strains. RESULTS: The two resistant strains (NIL-R and FS-R) exhibited moderate to high resistance to five insecticides (chlorfenapyr, emamectin benzoate, spinetoram, spinosad, and thiamethoxam), accompanied by significantly elevated GSTs activity. Phylogenetic analysis indicates that GSTs include 10 conserved delta and 7 diverse sigma members. The sigma subfamily has undergone a marked expansion due to gene duplication. Delta (FoGSTd1, d4, and d9) and sigma (FoGSTs1, s2, and s6) genes were significantly up-regulated in the resistant strains. RNAi showed specialized functional allocation among GSTs: delta GSTs mediated resistance to spinosad and chlorfenapyr, sigma GSTs were responsible for thiamethoxam resistance, and notably, cooperation between these subfamilies contributed to resistance against emamectin benzoate and spinetoram. Molecular docking and in vitro metabolism assays of FoGSTd9 and FoGSTs1 proteins further supported the functional allocation and cooperative roles of GST subfamilies. CONCLUSION: Our results indicate that F. occidentalis may coordinate GST subfamilies to achieve metabolic flexibility in response to multi-insecticide pressure. This survival strategy, mediated by mechanistic functional allocation and cooperative interactions among subfamilies, may contribute to energy conservation and reduced adaptive costs. Disruption of this coordinated mechanism represents a potential approach for overcoming resistance in agricultural pest populations.

Animals↗
PubMed1976

A model for areawide coordination of pediatric clinical experiences.

In the opinion of the project committee, clinical experience should be a primary consideration in the curriculum design process, not merely a stepsister to the cognitive aspects. Further, clinical experiences enable practitioners to develop the competencies required for meeting the needs of people they serve; thus, educational objectives should be based on the present and future health care needs of the consumers. In this project, the nursing needs of the child/family have been carefully delineated, and the available learning environments have been identified and assessed. One educational constraint unique to clinical practice is that the immediate welfare of the client must supersede the educational objectives of the learner. In this model, we have taken great pains to safeguard the client requirements. The person who is ill--especially the child--is vulnerable to fatigue, fright, insecurity, and sensory overload. The quotas developed for this study provide essential learning for the student but at the same time protect the integrity of the patient. Intensive study of clinical learning experiences by nursing is long overdue. We believe we have described one approach toward facilitating educationally sound curriculum and clinical decisions. The model as it stands provides variables, parameters, conditions, and assumptions which can now be manipulated and tested by those seeking answers to clinical resource allocation. Only by careful allocation and cooperative use of clinical facilities is it possible to provide appropriate learning experiences while maintaining the integrity of the care process.

Age Factors↗
PubMed1978

The economic cost of illness: fiscal 1975.

In 1963, Rice estimated the costs of illness and then allocated these costs by disease. She and Cooper in 1972 updated the original estimates and developed a more sophisticated methodological approach. This paper updates further the costs of illness to 1975 and presents further methodological changes. Analysis of the direct and indirect costs of illness for 1975 reveals that the upward trend into total costs continued, reaching $264 billion. The indirect costs are loss of earnings due to morbidity or premature mortality estimated at various discount rates allocated into 18 categories by disease. The direct costs include such payments as those made for hospital care, physician services, and drugs which are allocated by disease and unallocated costs such as construction and research. The proportion of total costs due to premature mortality were found to drop slightly from 1972 to 1975, while the morbidity share increased slightly. Direct costs account for approximately the same share of total illness in 1975 as in 1972. The proportion of total costs accounted for by direct costs varies directly with the discount rate selected, with the direct costs accounting for 50 per cent of the total at the 10 per cent discount rates and 37 per cent at 2.5 per cent rate. The proportion due to morbidity costs also varies directly with the discount rate, although the changes are small. There is an inverse relationship between the share for premature mortality costs and discount rate.

Direct Service Costs↗
PubMed1979

Alternate-day versus intermittent prednisone in frequently relapsing nephrotic syndrome. A report of "Arbetsgemeinschaft für Pädiatrische Nephrologie".

23 children with frequently relapsing minimal-change nephrotic syndrome were treated with alternate-day prednisone (35 mg/m2/48 h) and 25 other patients were treated with intermittent prednisone (40 mg/m2 on three consecutive days out of seven) for six months. This was followed by six months without any maintenance steroid treatment except when relapse required a short period of prednisone therapy until remission. The number of relapsers was significantly lower on alternate-day than on intermittent treatment. In the alternate-day group, the number of relapsers and the rate of relapse was significantly less before treatment withdrawal; in the intermittent group, only the number of relapsers was reduced. An alternate-day regiment is therefore preferable to the intermittent regimen in the interrupted steroid treatment of children with nephrotic syndrome.

Adolescent↗
PubMed1978

Hematologic observations made in patients with acute respiratory distress syndrome in the cooperative ECMO project.

In a recently completed three-year multicenter trial, 90 individuals with adult acute respiratory distress syndrome (ARDS) were randomly allocated to conventional therapy with or without long-term extracorporeal membrane oxygenation (ECMO). This study conclusively demonstrated that ARDS is associated with frequent major bleeding and thrombotic episodes and that the bleeding correlates best with the degree of thrombocytopenia and is enhanced by the machine. Neither heparin's therapeutic efficacy nor its ability to increase bleeding could be proven. ARDS is associated with a complex coagulation disturbance. Besides thrombocytopenia, there were lowered circulating levels of factors VII and XII which may be related to changes in the pulmonary endothelium. ECMO was associated with relative leukopenia and a marked shift to immature circulating leukocytes. Further studies are needed to better define the clinical importance of thrombosis and bleeding in the lung, the role for heparin in treatment, and the meaning of reductions in coagulation factors in defining the course, prognosis and response to therapy of patients with ARDS.

Acute Disease↗
PubMed1979

Coronary-artery bypass surgery in stable angina pectoris: Survival at two years. European Coronary Surgery Study Group.

768 men aged under 65 with angina pectoris, at least 50% obstruction in two or more major vessels, and a left-ventricular ejection fraction greater than or equal to 0.5 took part in a prospective randomised trial of the effect of coronary-artery bypass on prognosis. 373 patients were alloted to medical and 395 to surgical treatment. There was no significant difference between the two groups in the distribution of variables recorded at the time of randomisation. 1. "surgical" patient was lost to follow-up. 26 "surgical" patients did not undergo surgery and 50 "medical" patients were operated on. All these 76 patients were retained in their original treatment groups for the analysis. At 2 years there was no significant difference in mortality between the two groups. A significant difference was, however, found in the subset of patients with three-vessel disease, survival being significantly better for surgical patients. Operative (in-hospital) mortality was 3.6% in all operated patients and 1.5% in the last third. On average, 1.9 grafts per patient were inserted in the two-vessel-disease subgroup and 2.4 grafts per patient in the three-vessel-disease subgroup. Graft-patency rate was 90% within 9 months and 77% between 9 and 18 months after surgery. Symptomatic improvement was significantly better and deterioration less in the surgical group.

Adrenergic beta-Antagonists↗
PubMed1979

Research related to validation of treatment modalities by large-scale clinical trials.

The history of randomized, controlled, clinical trials is reviewed. Cooperative clinical trials are reviewed and summarized, and specific needs for future trials are identified. Improved policy on resource allocation decisions for clinical trials vs other forms of research is necessary, particularly as such trials begin to translate improved therapeutic knowledge into community level disease control.

American Heart Association↗
PubMed1978

Daunomycin, cytosine arabinoside and 6-thioguanine (DAT) vs vincristine, cytosine arabinoside and 6-thioguanine (VAT) in the induction treatment of acute nonlymphocyte leukemia: a randomized collaborative study.

One hundred patients were entered in a cooperative study comparing the efficacy of two different regimens in the induction treatment of acute nonlymphocytic leukemia (ANLL). Patients were randomly allocated to receive either the DAT or VAT combination; half of the patients were also randomized to receive CNS prophylaxis including intrathecal methotrexate + prednisone and cranial irradiation. Consolidation and maintenance therapy were uniform in responding patients. Out of 82 evaluable patients 41 (50%) attained complete remission (CR) with no significant difference between the two regimens. Median remission duration was slightly longer in the DAT group (32.5 vs 22 weeks); median survival was 34 weeks for all evaluable patients with no difference between the two schedules. Meningeal relapse occurred only in two patients after 19 and 99 weeks of continuous remission. Fourteen patients are still alive after 61 to greater than or equal to 155 weeks, of whom seven are in their initial remission (six in the DAT and one in the VAT group). We conclude that 1) DAT and VAT are equally effective in inducing CR in a high proportion of ANLL patients; 2) until marrow remission can be prolonged significantly, preventing CNS leukemia will not have any significant impact of the course of ANLL.

Adolescent↗
PubMed2026

Durvalumab and tremelimumab, with or without lenvatinib, combined with transarterial chemoembolisation in participants with embolisation-eligible hepatocellular carcinoma (EMERALD-3): a global, randomised, open-label, sponsor-blinded, phase 3 study.

BACKGROUND: Transarterial chemoembolisation (TACE), a standard treatment for embolisation-eligible hepatocellular carcinoma (HCC), induces tumour immune responses. Single tremelimumab regular interval durvalumab (STRIDE) is a standard treatment in advanced HCC. In this phase 3 trial, we assessed the efficacy and safety of STRIDE, with or without lenvatinib, plus TACE, in participants with embolisation-eligible HCC. METHODS: EMERALD-3 is a phase 3, randomised, open-label, sponsor-blinded study, conducted at 177 medical sites in 21 countries. Eligible participants were 18 years or older (aged &#x2265;21 years in Egypt or Singapore) at screening and had confirmed HCC (by imaging or histopathologically from biopsy specimen, surgery, or both) not amenable to curative surgery, curative ablation, or transplantation but amenable to TACE. Participants had Child-Pugh class A liver function, an Eastern Cooperative Oncology Group performance status of 0-1, and at least one measurable target intrahepatic lesion per modified Response Evaluation Criteria in Solid Tumours. Participants were randomly allocated in a 1:1:1 ratio to receive STRIDE plus lenvatinib plus TACE, STRIDE plus TACE, or TACE until each group reached its preplanned enrolment target of 175 participants. After the STRIDE plus TACE group reached its enrolment target, randomisation was adjusted to continue in a 1:1 ratio between the STRIDE plus lenvatinib plus TACE group and TACE group until approximately 275 participants were enrolled in each of these two groups. Randomisation used a centrally assigned interactive response technology system, stratified by region, baseline tumour burden, and previous palliative embolisation. In the STRIDE plus lenvatinib plus TACE group, on the first day, participants were given 300 mg tremelimumab intravenously, followed by 1500 mg durvalumab plus oral lenvatinib (8 mg for <60 kg bodyweight or 12 mg for &#x2265;60 kg bodyweight); participants then received 1500 mg durvalumab every 4 weeks plus once-daily lenvatinib for up to 36 cycles. In the STRIDE plus TACE group, participants were given 300 mg tremelimumab and 1500 mg durvalumab intravenously on the first day, followed by 1500 mg durvalumab every 4 weeks. The technique and number of TACE procedures were at the investigators' discretion, with the first procedure administered at least 7 days after the first dose of durvalumab in the two investigation treatment groups and within 7 days of random allocation in the TACE group. The primary endpoint was progression-free survival for STRIDE plus lenvatinib plus TACE versus TACE. Key secondary endpoints were overall survival for STRIDE plus lenvatinib plus TACE versus TACE and progression-free survival and overall survival for STRIDE plus TACE versus TACE. This study was registered with ClinicalTrials.gov (NCT05301842), with enrolment completed. FINDINGS: From March 28, 2022, to Nov 20, 2024, 1124 participants were screened. The full analysis set comprised 760 participants, who were randomly allocated to STRIDE plus lenvatinib plus TACE (n=293), STRIDE plus TACE (n=175), or TACE (n=292). 633 (83%) participants were male and 127 (17%) were female; 548 (72%) were Asian. At the first data cutoff (Sept 2, 2025); the overall median follow-up for progression-free survival was 10&#xb7;0 months (IQR 4&#xb7;6-17&#xb7;2); median follow-up for progression-free survival was 11&#xb7;0 months (IQR 4&#xb7;8-18&#xb7;4) for STRIDE plus lenvatinib plus TACE and 8&#xb7;3 months (4&#xb7;1-15&#xb7;5) for TACE. Median progression-free survival was 13&#xb7;0 months (95% CI 12&#xb7;2-16&#xb7;7) for STRIDE plus lenvatinib plus TACE versus 9&#xb7;8 months (8&#xb7;0-11&#xb7;4) for TACE (HR 0&#xb7;70 [95% CI 0&#xb7;57-0&#xb7;86]; p=0&#xb7;0007). At the second data cutoff (Feb 23, 2026) and a median follow-up for overall survival of 24&#xb7;6 months (IQR 16&#xb7;5-31&#xb7;5) for STRIDE plus lenvatinib plus TACE and 22&#xb7;9 months (14&#xb7;9-30&#xb7;2) for TACE, median overall survival was 39&#xb7;5 months (95% CI 34&#xb7;1-not reached) for STRIDE plus lenvatinib plus TACE and 34&#xb7;7 months (28&#xb7;8-not reached) for TACE (HR 0&#xb7;84 [95% CI 0&#xb7;65-1&#xb7;09]; p=0&#xb7;18). At this data cutoff, median progression-free survival was 12&#xb7;9 months (95% CI 10&#xb7;2-15&#xb7;9) for STRIDE plus TACE and 8&#xb7;1 months (6&#xb7;5-10&#xb7;2) for the first 175 participants randomised to TACE (HR 0&#xb7;71 [95% CI 0&#xb7;56-0&#xb7;91]), with median follow-up of 10&#xb7;3 months (IQR 4&#xb7;6-23&#xb7;7) for STRIDE plus TACE and 7&#xb7;7 months (3&#xb7;0-18&#xb7;5) for the first 175 participants randomly allocated to TACE. The most common adverse events of maximum grade 3 or 4 were hypertension (34 [12%] of 287) for STRIDE plus lenvatinib plus TACE, post-embolisation syndrome and anaemia (ten [6%] of 175 each) for STRIDE plus TACE, and post-embolisation (17 [6%] of 290) for TACE. 184 (64%) participants receiving STRIDE plus lenvatinib plus TACE, 89 (51%) receiving STRIDE plus TACE, and 68 (23%) receiving TACE had serious adverse events. Treatment-related adverse events with an outcome of death during the treatment-emergent period occurred in seven (2%) of 287 participants who received STRIDE plus lenvatinib plus TACE (two for myocarditis; and one each for hepatic failure, haemophagocytic lymphohistiocytosis, septic shock, cardiac failure, and unknown cause), none of 175 participants who received STRIDE plus TACE, and two (1%) of 290 participants who received TACE (one each for acute myocardial infarction and unknown cause). INTERPRETATION: STRIDE plus lenvatinib plus TACE showed a statistically significant progression-free survival improvement versus TACE. These findings support a STRIDE-based regimen as a potential new treatment option for people with embolisation-eligible HCC; additional follow-up is being conducted for final analysis of overall survival across treatment groups. FUNDING: AstraZeneca.

Adult↗
PubMed1976

The financing and the economic efficiency of rural health services in the People's Republic of China.

This paper studies the resource allocation in the provision of health care services at the local level in the People's Republic of China. The subject of health financing and the effectiveness and cost of this medical cooperative service in the country's rural areas are evaluated. The conclusion drawn is that, with China's agricultural economic framework, the adoption of barefoot doctor services and the promotion of herbal medicine are cost-minimizing approaches that enable local political units to be financially self-supporting with regard to medical services. Based on a few samples at brigade or commune level, the results indicate that the barefoot doctor services are economically valuable. Furthermore, the sense of security and a point of entry into the health care system that the barefoot doctors can provide for lower-income peasants are by no means a minor noneconomic benefit. Some of their experiences may be useful to other developing countries.

China↗
PubMed1976

The VA cooperative randomized study of surgery for coronary arterial occlusive disease II. Subgroup with significant left main lesions.

From a large cooperative prospective randomized study, data relating to a subgroup of 113 patients with angina pectoris and a significant lesion of the left main coronary artery were analyzed. Of these patients, 53 had been randomly allocated to a medical treatment group and 60 to a surgical treatment group. The former group received conventional medical treatment, while the surgical treatment group received one or more aortocoronary saphenous vein bypass grafts. Important risk factors were approximately uniformly distributed between the two groups. Both are being followed up to 60 months (average follow-up, 30 months). To date, 12 of 60 surgical patients (20%) and 19 of 53 medical patients (36%) died (P less than 0.06). The operative (30-day) mortality declined from a rate of 25% for the first 2 years of the study to 7% for the last 3 years. Of patients randomized in the latter 3 years of the study, 12 of 41 medical patients (29%) and three of 42 surgical patients (7%) died (P less than 0.01). The average follow-up period in this group was 24 months. The proportion surviving 24 months was clearly larger in the surgically treated group (P less than 0.02). The difference in the proportion of patients surviving after surgery as compared with medical treatment was greatest in patients with additional significant disease involving the right coronary artery, with or without left ventricular dysfunction. Relief of angina as assessed by an "anginal score" was also better in surgical patients to a significant degree. Graft-patency rates correlated well with relief of angina, but objective studies including treadmill testing are not yet available.

Angina Pectoris↗
PubMed1979

Designing and analyzing clinical trials which allow institutions to randomize patients to a subset of the treatments under study.

When patients have been randomized between different sets of treatments the treatment groups are not strictly comparable. However, if one can assume that biases which are introduced affect the outcome additively, then one can compare treatments across these institutional options. This is illustrated for dichotomous response data and censored survival data. We show how the sample size must be increased to allow for this analysis and how the randomization should be weighted to obtain the best power. These results have application to simultaneous trials by different cooperative groups which have one or more common treatment arms.

Clinical Trials as Topic↗
PubMed1979

A prospective, controlled trial of six forms of hormone replacement therapy given to postmenopausal women.

This study was undertaken to investigate the effect of various forms of hormone replacement therapy (HRT) upon postmenopausal women while controlling as many variables as possible. It was felt that the age, duration of amenorrhoea and the general health of the patients should be as comparable as possible and that each patient should provide her own pretherapy and post-therapy control data. In addition, it was felt that any placebo effect should be investigated and the patients were therefore randomly allocated to placebo tablets or one of six available forms of HRT. The age/sex registers of two large general practices were scrutinized and all women between 49 and 54 years of age were asked to cooperate; for a variety of reasons only 56 women were suitable and willing to take part in the project, yielding 8 women for each of the seven possible therapy groups. Blood samples were taken at 7-day intervals three times before therapy was given and the mean of the three values was used as the control value. The women returned on day 21 of each subsequent therapy cycle for six consecutive months and finally three months after discontinuing therapy. From the data the following broad conclusions can be drawn: (i) some women have classic symptoms of hot flushes and sweating despite high endogenous oestrogen concentrations; (ii) vaginal cytology is a relatively poor indicator of endogenous oestrogen status; (iii) while follicle stimulating hormone (FSH) and luteinizing hormone (LH) concentrations are reduced on HRT neither is decreased to anywhere near premenopausal values while prolactin is unaffected; (iv) plasma cholesterol levels are reduced on HRT, the pulse rate is slower and both systolic and diastolic blood pressure are reduced to a small but significant extent; (v) there is no adverse effect upon blood clotting; and (vi) most women experience significant or complete relief of symptoms on all forms of HRT as do some women taking a placebo. The combined preparations containing an oestrogen and progestogen produced vaginal bleeding in only 80 per cent of the women. Thus protection by regular endometrical shedding may not be afforded to all women. As vaginal bleeding is unacceptable to most women if they can achieve the same symptomatic relief without inducing menstruation, it is suggested that women have a low dose oestrogen preparation prescribed cyclically for 6 to 12 months. If therapy is to be maintained for a longer time, uterine curretage should be undertaken at regular intervals to exclude the possibility of endometrial carcinoma developing.

Climacteric↗
PubMed1979

Metabolic interaction between amitriptyline and perphenazine in psychiatric patients.

1. Steady-state plasma level samples of sixty-five schizophrenic patients from two psychiatric hospitals assigned to three treatment groups (amitriptyline 150 mg/day, perphenazine 20 mg/day and a combination of amitriptyline and perphenazine at 150 mg and 20 mg/day) were assayed for amitriptyline (AT), endogenous nortriptyline (NT) and perphenazine (PPZ) using gas-liquid chromatography. 2. Results reveal that AT and NT levels are independent of sex and hospital environment. 3. PPZ significantly increased the steady-state NT plasma levels, probably through inhibition of the hydroxylation biotransformation pathway, but had no effect on AT levels, thus indicating that PPZ has no influence on the desmethylation pathway, or alternatively, the hydroxylation of AT.

Adult↗
PubMed1979

Redistribution of body heat during anaesthesia. A comparison of halothane, fentanyl and epidural anaesthesia.

Epidural anaesthesia and high dose fentanyl (50 micrograms/kg) when used to supplement nitrous oxide and oxygen anaesthesia for a standard lower abdominal operation were associated with a mean fall in deep body temperature, as measured in the external auditory meatus, of 0.46 degrees C and 0.6 degrees C/hr respectively. This is significantly different from the mean values of 0.14 degrees C and 0.2 degrees C/hr which were recorded when moderate dose fentanyl (10 micrograms/kg) or 0.5% halothane were used to supplement anaesthesia. When mean skin temperature is combined with the core temperature to provide an estimate for total body heat, there is no difference between the groups. Redistribution of body heat occurs and this may be related to reduced adrenergic stimulation and altered regional blood flow. Where the facilities and environments are inadequate for the maintenance of normothermia, care should be taken in the choice of anaesthetic technique. In the recovery period mean body heat gain showed a wide scatter of results but those patients receiving epidural anaesthesia were slow to rewarm despite a high incidence of shivering in this group. The implications of this are discussed.

Adult↗