Prematurity is associated with volumetric reductions in specific brain areas such as the hippocampus and with metabolic changes that can be detected by spectroscopy. Short echo time (35 ms) Proton magnetic resonance spectroscopy (1H MRS) was performed to assess possible medial temporal lobe metabolic abnormalities in 21 adolescents with preterm birth (mean age: 14.8, SD: 1.3) compared with an age-matched control sample (mean age: 14.8, SD: 1.6). 1H MRS spectra were analyzed with linear combination model fitting, obtaining the absolute metabolite concentrations for Creatine (Cr), and myo-inositol (Ins). In addition, the following metabolite sums were measured: total Cho (glycerophospho-choline + phosphocholine), total N-acetyl-aspartate + N-acetyl-aspartylglutamate (NA), and total Glx (glutamate + glutamine). A stereological analysis was performed to calculate hippocampal volume. Absolute Cr, and total NA values were decreased in the preterm group (p = 0.016; p = 0.002, respectively). The preterm also showed a hippocampal reduction (p < 0.0001). Significant relationships were found between gestational age and different metabolites and the hippocampal volume. Moreover, hippocampal volume correlated with brain metabolites in the whole sample. Results demonstrate that prematurity affects medial temporal lobe metabolites, and that the alteration is related to structural changes, suggesting that the cerebral changes persist until adolescence. 相似文献
Objectives. We assessed the effectiveness of the penalty points system (PPS) introduced in Spain in July 2006 in reducing traffic injuries.Methods. We performed an evaluation study with an interrupted time–series design. We stratified dependent variables—numbers of drivers involved in injury collisions and people injured in traffic collisions in Spain from 2000 to 2007 (police data)—by age, injury severity, type of road user, road type, and time of collision, and analyzed variables separately by gender. The explanatory variable (the PPS) compared the postintervention period (July 2006 to December 2007) with the preintervention period (January 2000 to June 2006). We used quasi-Poisson regression, controlling for time trend and seasonality.Results. Among men, we observed a significant risk reduction in the postintervention period for seriously injured drivers (relative risk [RR] = 0.89) and seriously injured people (RR = 0.89). The RRs among women were 0.91 (P = .095) and 0.88 (P < .05), respectively. Risk reduction was greater among male drivers, moped riders, and on urban roads.Conclusions. The PPS was associated with reduced numbers of drivers involved in injury collisions and people injured by traffic collisions in Spain.Traffic injuries cause considerable mortality and morbidity worldwide. Since 2004, traffic deaths in Spain have followed a downward trend. However, more than 135 000 road users were injured and more than 4000 were killed in 2005, numbers which placed Spain above the mean for the European Union (EU; ranked 13th of the 25 member states).1The penalty points system (PPS), introduced in Spain on July 1, 2006, attempts to deter drivers from committing traffic offenses. Because the PPS does not exclusively depend on monetary penalties, it affects all drivers irrespective of their income level.2 In Spain, drivers start with a 12-point license (8-point for novice drivers), and the points are gradually removed if certain traffic violations are committed, such as exceeding the speed limit, driving while intoxicated, or using a hand-held mobile phone, culminating in license suspension if all points are lost. Only serious violations result in loss of points, with the number of points removed varying with the severity of the offense (3 Several months before its introduction, the PPS was announced via a publicity campaign in all news media, and was included in the media agenda, giving rise to public debate.
TABLE 1
Number of Points Subtracted From the Driver''s License, by Type of Offense, in Spain''s Penalty Points System (PPS): Spain, 2000–2007
2 Points
3 Points
4 Points
6 Points
Speeding > 20 km/h to 30 km/h over the limit (< 50% of the limit)
Speeding > 30 km/h to 40 km/h over the limit (< 50% of the limit)
Speeding > 40 km/h over the limit (< 50% of the limit)
Driving with a blood alcohol content 0.25 mg/L to 0.50 mg/L (0.15 mg/L to 0.30 mg/L professionals and novices)
Speeding > 50% of the limit, at least > 30 km/h
Driving without headlights when headlights are required
Changing direction illegally
Not obeying stop signs, traffic lights, right-of-ways, and other traffic rules
Overtaking dangerously or in locations with limited visibility
Driving with a blood alcohol content > 0.50 mg/L (> 0.30 mg/L for professionals and novices)
Circulating with a person aged < 12 y on a moped or motorcycle, with the statutory exceptions
Failing to comply with the safety distance
Hindering other vehicles from overtaking
Overtaking putting cyclists at risk
Driving under the influence of drugs or other substances
Using systems to avoid traffic officers’ surveillance or to detect speed cameras
Driving while using earphones or hand-held mobile phones
Reversing in motorways
Careless driving
Refusing analysis of alcohol, drugs, and other similar behaviors
Stopping or parking at dangerous places (e.g., road junction, tunnel)
Driving without seat belt, helmet, and other compulsory safety devices
Not obeying traffic officers’ signals
Driving without the appropriate license
Dangerous driving, wrong way, races, and other similar behaviors
Stopping or parking disturbing circulation, pedestrians, or in lanes reserved for public transport
Driving on a motorway with a forbidden vehicleThrowing objects on the road that may produce a fire or accidents
Driving with > 50% more than the authorized number of occupants
For professional drivers, exceeding the maximum permitted uninterrupted driving hours by > 50% or reducing subsequent rest hours by > 50%
Open in a separate windowAlthough 20 of the 27 EU member states had adopted a PPS by 2007, to date, few countries have published studies assessing its effectiveness in terms of road safety.4–9 The few studies that have been published are generally simple before–after analyses, with the exception of those by Zambon et al.4 and Pulido et al.9 In addition, most studies have assessed only the impact of PPS on the overall number of people injured or killed, and have not considered gender, type of road user, and other variables that could help to identify in which road user profiles the PPS is effective and in which profiles it is ineffective. In Spain, the effectiveness of the PPS has been assessed only for overall numbers of fatalities on nonurban roads.9 In addition, none of those studies have analyzed changes in risk among drivers, who are the main target of the PPS.Our objective was to assess the effectiveness of the PPS in reducing the number of drivers involved in injury collisions (i.e., traffic collisions resulting in injury) and the number of people injured in traffic collisions in Spain. Our hypothesis was that the PPS is effective in reducing traffic injuries and that its effectiveness varies with gender, age, injury severity, type of road user, road type, and time of collision. 相似文献
Prostate cancer (PC) is one of the tumours with the highest incidence in recent years. PC therapies have several adverse effects. A panel consensus recommendation has been made to prevent or ameliorate complications in PC treatment to improve quality of life.
Material and methods
Fifteen specialists have met to analyse the different toxicities associated with PC treatment. Each medical specialist performed a National Library of Medicine PubMed search citations searching about these secondary effects and his speciality from 1999 to 2009 to propose measures for their prevention/amelioration.
Results
Surgery is associated with incontinence and impotence. Radiotherapy can produce acute, late urological and gastrointestinal toxicity. Brachytherapy can produce acute urinary retention. Chemotherapy is associated with haematotoxicity, peripheral neuropathy and diarrhoea, and hormone therapy can produce osteoporosis, metabolic syndrome, cognitive and muscular alterations, cardiotoxicity, etc.
Conclusions
Improvement in surgical techniques and technology (IMRT/IGRT) can prevent surgical and radiotherapeutic toxicity, respectively. Brachytherapy toxicity can be prevented with precise techniques to preserve the urethra. Chemotherapy toxicity can be prevented with personalised schedules of treatment and close follow-up of iatrogenia and hormone therapy toxicity can be prevented with close follow-up of possible secondary effects. 相似文献
This phase I, four-arm, open-label study (NCT01347866) evaluated the PI3K/mTOR inhibitors PF-04691502 (arms A, B) and gedatolisib (PF-05212384; arms C, D) in combination with the MEK inhibitor PD-0325901 (arm A, D) or irinotecan (arm B, C) in patients with advanced solid tumors.
Objectives
Primary endpoint was dose-limiting toxicity with each combination. Secondary endpoints included safety, pharmacokinetics and preliminary antitumor activity.
Patients and Methods
Dose escalation followed a 3 + 3 design in arm C and a zone-based design in arm D.
Results
The PF-04691502 combination arms were closed prematurely due to low tolerability, and the maximum tolerated doses (MTDs) were not determined for either arm. The MTD for the combination of gedatolisib with irinotecan 180 mg/m2 was estimated to be 110 mg weekly and for the combination with PD-0325901 was not reached at the highest dose evaluated (gedatolisib 154 mg weekly). Plasma concentrations of gedatolisib were generally similar across dose groups in arm C (with irinotecan) and arm D (with PD-0325901). Frequent dose delays or dose reductions were required for both combinations, potentially preventing sustained therapeutic drug concentrations. Gedatolisib plus irinotecan produced a response rate of ~5% and clinical benefit in 16% of patients with advanced colorectal cancer (progression-free survival, 2.8 months). Preliminary evidence of clinical activity was observed with gedatolisib plus PD-0325901 in patients with ovarian cancer (three partial responses, n = 5) or endometrial cancer (one partial response, n = 1) and KRAS mutations.
Conclusions
Further evaluations of gedatolisib are warranted in patients with advanced solid malignancies.
