Effects of continuous cocaine administration on schedule-controlled behavior in rhesus monkeys

The behavioral effects of continuous infusion of cocaine for prolonged periods were examined in rhesus monkeys responding under fixed-ratio (FR) or fixed-interval (FI) schedules of food presentation. Operant behavior was examined every 6h for 30min (FR) or 60min (FI) while saline or increasing doses of cocaine (4.0-32mg/kg/day) were continuously (24h/day) infused through an intravenous catheter. Cocaine initially reduced FR responding and tolerance developed to doses as high as 32mg/kg/day over periods of 10 to 35 days. When continuous infusion of cocaine (32mg/kg/day) was terminated after 50-80 total days of cocaine exposure, behavior was disrupted for several days in three of four monkeys. These behavioral disruptions were reversed when cocaine (0.062-0.25mg/kg) was administered i.v. 10min before sessions in which responding was typically suppressed, suggesting that behavioral dependence on cocaine had developed. Continuous infusion of cocaine also initially decreased the rate of FI 60s responding and tolerance developed to doses of 4.0 and 8.0mg/kg/day. Behavioral disruptions were not consistently observed when infusion of cocaine (8.0mg/kg/day) was terminated after up to 110 total days of cocaine exposure. Although reinforcement loss was comparable under the two schedules of reinforcement, the rate and extent of tolerance development varied between the two schedules of reinforcement. Therefore, behavioral factors in addition to reinforcement loss contribute to the development of cocaine tolerance. In addition, the data suggest that behavioral dependence upon cocaine can develop, but only under extreme exposure conditions.     

SonoWand, an ultrasound-based neuronavigation system

OBJECTIVE: We have integrated a neuronavigation system into an ultrasound scanner and developed a single-rack system that enables the surgeon to perform frameless and armless stereotactic neuronavigation using intraoperative three-dimensional ultrasound data as well as preoperative magnetic resonance or computed tomographic images. The purpose of this article is to describe our two-rack prototype and present the results of our work on image quality enhancement. DESCRIPTION OF INSTRUMENTATION: The system consists of a high-end ultrasound scanner, a modest-cost computer, and an optical positioning/digitizer system. Special technical and clinical efforts have been made to achieve high image quality. A special interface between the ultrasound instrument and the navigation computer ensures rapid transfer of digital three-dimensional data with no loss of image quality. OPERATIVE TECHNIQUE: The positioning system tracks the position and orientation of the patient, the ultrasound probe, the pointer, and various surgical instruments. This makes it possible to update the three-dimensional map during surgery and navigate by ultrasound data in a similar manner as with magnetic resonance data. METHODS: The two-rack prototype has been used for clinical testing since November 1997 at the University Hospital in Trondheim. EXPERIENCE AND RESULTS: The image quality improvements have enabled us, in most cases, to extract information from ultrasound with clinical value similar to that of preoperative magnetic resonance imaging. The overall clinical accuracy of the ultrasound-based navigation system is expected to be comparable to or better than that of a magnetic resonance imaging-based system. CONCLUSION: The SonoWand system enables neuronavigation through direct use of intraoperative three-dimensional ultrasound. Further research will be necessary to explore the potential clinical value and the limitations of this technology.     

Variation in hospital charges for total joint arthroplasty: an investigation of physician efficiency

Total joint arthroplasty is a common procedure for which consistent, clinically satisfactory outcomes are expected. Data from 796 total joint procedures performed by 20 surgeons at one center were evaluated to identify sources of variability in costs (as measured by hospital charges) where clinical outcome is expected to remain constant. Stepwise multivariate regression characterized the contribution of six variables to hospital charges listed in order of explanatory power: postoperative length of stay, surgical time, patient preoperative morbidity, units of blood transfused, perioperative complications, and procedure type (hip or knee) accounted for 46% of variability in hospital charges (multiple R2). In a subsequent analysis, after statistical adjustment for preoperative comorbid diagnoses, the sampling distribution of mean values for surgical time, total units of blood transfused, and total hospital charges were summarized and compared among surgeons. Despite adjustment for comorbid diagnoses, substantial variation and significant differences remained between surgeons in markers of resource utilization and "surgical efficiency." These findings suggest there is substantial variability in hospital charges not attributable to patient characteristics or category of procedure--a distinct and economically significant portion of this variability is practitioner specific.     

Risk-Adjusted Cancer Screening and Prevention (RiskAP): Complementing Screening for Early Disease Detection by a Learning Screening Based on Risk Factors

BackgroundRisk-adjusted cancer screening and prevention is a promising and continuously emerging option for improving cancer prevention. It is driven by increasing knowledge of risk factors and the ability to determine them for individual risk prediction. However, there is a knowledge gap between evidence of increased risk and evidence of the effectiveness and efficiency of clinical preventive interventions based on increased risk. This gap is, in particular, aggravated by the extensive availability of genetic risk factor diagnostics, since the question of appropriate preventive measures immediately arises when an increased risk is identified. However, collecting proof of effective preventive measures, ideally by prospective randomized preventive studies, typically requires very long periods of time, while the knowledge about an increased risk immediately creates a high demand for action.SummaryTherefore, we propose a risk-adjusted prevention concept that is based on the best current evidence making needed and appropriate preventive measures available, and which is constantly evaluated through outcome evaluation, and continuously improved based on these results. We further discuss the structural and procedural requirements as well as legal and socioeconomical aspects relevant for the implementation of this concept.     

抑郁障碍患者主观与客观认知功能的差异性研究

背景 抑郁障碍患者的主观认知功能与客观认知功能存在差异。目前,关于主客观认知功能差异影响因素的研究有限。目的 探索抑郁障碍患者主观和客观认知功能的差异及其影响因素,为进一步理解抑郁障碍患者认知功能受损情况提供参考。方法 纳入2022年1月13日—2023年12月11日在成都市第四人民医院门诊就诊或住院治疗的、符合《精神障碍诊断与统计手册（第5版）》（DSM-5）抑郁障碍诊断标准的77例患者为研究对象。采用蒙哥马利-艾森贝格抑郁量表（MADRS）评定患者抑郁症状严重程度,采用抑郁感知缺陷问卷（PDQ-D）和中国简版神经认知成套测验（C-BCT）分别评定患者的主观认知功能和客观认知功能,采用席汉残疾量表（SDS）评定患者的社会功能,以临床总体印象量表-疾病严重程度量表（CGI-SI）评定患者病情严重程度。采用Pearson相关分析考查年龄、受教育年限、MADRS总评分、SDS总评分、CGI-SI评分与主客观认知功能及其差异的相关性。采用多元线性回归探索主客观认知功能差异的影响因素。结果 是否用药的抑郁障碍患者PDQ-D总评分和主客观认知功能差异（D值）比较差异均有统计学意义（t=-4.2...     

Adjuvant capecitabine-containing chemotherapy benefit and homologous recombination deficiency in early-stage triple-negative breast cancer patients

Background The addition of adjuvant capecitabine to standard chemotherapy of early-stage triple-negative breast cancer (TNBC) patients has improved survival in a few randomised trials and in meta-analyses. However, many patients did not benefit. We evaluated the BRCA1-like DNA copy number signature, indicative of homologous recombination deficiency, as a predictive biomarker for capecitabine benefit in the TNBC subgroup of the FinXX trial.Methods Early-stage TNBC patients were randomised between adjuvant capecitabine-containing (TX + CEX: capecitabine-docetaxel, followed by cyclophosphamide-epirubicin-capecitabine) and conventional chemotherapy (T + CEF: docetaxel, followed by cyclophosphamide-epirubicin-fluorouracil). Tumour BRCA1-like status was determined on low-coverage, whole genome next-generation sequencing data using an established DNA comparative genomic hybridisation algorithm.Results For 129/202 (63.9%) patients the BRCA1-like status could be determined, mostly due to lack of tissue. During a median follow-up of 10.7 years, 35 recurrences and 32 deaths occurred. Addition of capecitabine appears to improve recurrence-free survival more among 61 (47.3%) patients with non-BRCA1-like tumours (HR 0.23, 95% CI 0.08–0.70) compared to 68 (52.7%) patients with BRCA1-like tumours (HR 0.66, 95% CI 0.24–1.81) (P-interaction = 0.17).Conclusion Based on our data, patients with non-BRCA1-like TNBC appear to benefit from the addition of capecitabine to adjuvant chemotherapy. Patients with BRCA1-like TNBC may also benefit. Additional research is needed to define the subgroup within BRCA1-like TNBC patients who may not benefit from adjuvant capecitabine.Subject terms: Breast cancer, Translational research, Predictive markers, Breast cancer     

Response to Ozone in Volunteers with Chronic Obstructive Pulmonary Disease

Twenty-eight volunteers with chronic obstructive pulmonary disease were exposed to 0.0, 0.18, and 0.25 ppm ozone in purified air for 1-hr periods with light intermittent exercise, with exposure conditions presented in random order at 1-month intervals. No statistically significant changes attributable to ozone were found in forced expiratory performance or percent oxyhemoglobin (measured near the beginning and end of each exposure). No ozone-related changes in clinical status were found by interviews that included the time for 1 wk before to 1 wk after each exposure, except that a moderate increase in lower respiratory symptoms was reported by nonsmokers in 0.18 ppm exposures only. Thus, a slight decrement in hemoglobin saturation with ozone exposure (reported in two previous studies of chronic obstructive pulmonary disease subjects) may not be a common occurrence under typical ambient exposure conditions.