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1.

In this work we analysed the stepwise charging technique to find the limits from which it is beneficial in terms of load capacitance and charge–discharge frequency. We included in the analysis practical limitations such as the consumption of auxiliary logic needed to implement the technique and the minimum size of auxiliary switches imposed by the technology. We proposed an ultra-low-power logic block to push these limits and to obtain benefits from this technique in small capacitances. Finally, we proposed to use a stepwise driver in the driving of the gate capacitance of power switches in switched-capacitor (SC) DC–DC converters. We designed and manufactured, in a 130 nm process, a SC DC–DC converter and measured a 29% energy reduction in the gate-drive losses of the converter. This accounts for an improvement of 4% (from 69 to 73%) in the overall converter efficiency.

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The association between obesity, cancer and cardiovascular disease (CVD) has been demonstrated in animal and epidemiological studies. However, the specific role of visceral obesity on cancer and CVD remains unclear. Visceral adipose tissue (VAT) is a complex and metabolically active tissue, that can produce different adipokines and hormones, responsible for endocrine-metabolic comorbidities. This review explores the potential mechanisms related to VAT that may also be involved in cancer and CVD. In addition, we discuss the shared pharmacological treatments which may reduce the risk of both diseases. This review highlights that chronic inflammation, molecular aspects, metabolic syndrome, secretion of hormones and adiponectin associated to VAT may have synergistic effects and should be further studied in relation to cancer and CVD. Reductions in abdominal and visceral adiposity improve insulin sensitivity, lipid profile and cytokines, which consequently reduce the risk of CVD and some cancers. Several medications have shown to reduce visceral and/or subcutaneous fat. Further research is needed to investigate the pathophysiological mechanisms by which visceral obesity may cause both cancer and CVD. The role of visceral fat in cancer and CVD is an important area to advance. Public health policies to increase public awareness about VAT’s role and ways to manage or prevent it are needed.  相似文献   
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Tumor cells from eight freshly isolated cervical cancers (i.e., four adenocarcinomas and four squamous carcinomas) were analyzed for their production of the immune-inhibitory cytokine transforming growth factor-beta (TGF-beta) in vitro. All fresh adenocarcinomas secreted significant levels of TGF-beta (mean 397, range between 207 and 782 pg/ml/10(5) cells/48 hr). In contrast, no detectable TGF-beta was present in the supernatants from the four fresh squamous carcinoma cultures (P < 0.001). These data suggest that major differences in the secretion of the immunoinhibitory cytokine TGF-beta exist between squamous cell carcinomas and adenocarcinomas of the uterine cervix. Furthermore, these findings suggest that at least some of the differences in the natural biologic behavior, as well as in the response to radiation treatment, between these two histologic types of cervical cancer could be related to differences in secretion of this immune-inhibitory cytokine.  相似文献   
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The log-rank test is commonly used to assess therapeutic effect in prospective, randomised clinical trials. This test is sensitive to differences in survival between treatment groups at a specific endpoint, but cannot determine whether such a difference is due to an enhanced cure rate or an enhanced survival time among uncured patients. To investigate the clinical impact of such limitations, an algorithm was constructed to simulate clinical, randomised, adjuvant therapy trials in patients with a cured fraction of 0.27 and a median survival time for uncured patients of 3.4 years. Hypothetical therapies were introduced to increase rate of cure, increase median survival time, or achieve a combination of these effects. For 500 simulated patients recruited over a 5 year period and then followed for three additional years, a 50% enhancement of median survival time (to 5.1 years) led to a survival increase detectable at the P = 0.05 level in 780 of 1000 trials, whereas a 50% enhancement of cured fraction (to 40.5%) led to a detectable increase at the same level in only 449 of 1000 trials. These findings suggest that, in clinical trials of adjuvant therapy for stage 2 breast cancer, the log rank test may be more sensitive to increases in tumour-related survival time than to increases in cured fraction.  相似文献   
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There is no better place to test life-saving resuscitation interventions than in the prehospital setting. Patients rarely survive cardiac arrest if resuscitation techniques have failed before leaving the scene. Also, paramedics are usually very experienced in key initial resuscitative techniques, and they routinely operate under strict paramilitary protocol, resulting in better study compliance. In addition, the large study populations that are derived from emergency medical services (EMS) systems lead to faster study completion and statistically stronger data. Most important, by reinforcing standardized care, rigidly scrutinized trials improve patient care, regardless of the effect of the study intervention. The success of productive EMS research centers requires routine communication between hospital and EMS administrators and their medical directors, designation of mutually acceptable data collectors who guarantee confidentiality, reciprocal exchange of study data provided as educational seminars to the hospitals, commitments to support the budget requests of an EMS program and appropriate system modifications, inclusion of EMS personnel in study design from the very beginning, prospective education of the medical community and media before protocol implementation, an authoritative grassroots medical director, and a paramedic supervisor system.  相似文献   
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