Recently, a 1H-MRS method became available to quantify intramyocellular lipids (IMCL) non-invasively. Currently, little is known about the regulation of this lipid pool. During prolonged exercise of moderate intensity, non-plasma-derived fatty acids play an important role as an energy source; lipids located within the skeletal muscle are considered to be a major source for these fatty acids. To see whether IMCL are reduced by exercise, 12 male runners were studied before and after exercising at different workloads and duration. Six subjects participated in a non-competitive run (NCR), three runners in a competitive half marathon (HM, 21 km) and another three in a competitive marathon (M, 42 km). Intra- and extramyocellular lipids were quantified by 1H-MR spectroscopy in the tibialis anterior (TA) and soleus (SOL) muscles prior to and after the exercise bout. Moderate intensity (MI; 60-70% VO2max in NCR) with a mean exercise time (MET) ranging between 105-110 min decreased IMCL by 10 - 36% in both muscles. Prolonged MI exercise (MET 210-240 min; 68-70% VO2max in M) reduced IMCL by 42-57% in TA and 27 - 56% in SOL. In contrast, high intensity exercise (HI; MET 80-120 min; 83-85% VO2max in HM) did not alter IMCL in either muscle. Extramyocellular lipids (EMCL) did not show any significant change in any group. The data show that one bout of moderate-intensity (60-70% VO2max) aerobic exercise markedly reduces the IMCL in TA and SOL muscles in a time-dependent fashion as assessed by 1H-MRS. However, exercise of similar duration but higher workload (> 80% VO2max) does not reduce IMCL. These data suggest that both exercise duration and workload are important factors in determining the reduction of IMCL.
While they account for one-fifth of new cancer cases, rare cancers are difficult to study. A higher than average degree of uncertainty should be accommodated for clinical as well as for population-based decision making. Rules of rational decision making in conditions of uncertainty should be rigorously followed and would need widely informative clinical trials. In principle, any piece of new evidence would need to be exploited in rare cancers. Methodologies to explicitly weigh and combine all the available evidence should be refined, and the Bayesian logic can be instrumental to this end. Likewise, Bayesian-design trials may help optimize the low number of patients liable to be enrolled in clinical studies on rare cancers, as well as adaptive trials in general, with their inherent potential of flexibility when properly applied. While clinical studies are the mainstay to test hypotheses, the potential of electronic patient records should be exploited to generate new hypotheses, to create external controls for future studies (when internal controls are unpractical), to study effectiveness of new treatments in real conditions. Framework study protocols in specific rare cancers to stepwisely test sets of new agents, as from the early post-phase I development stage, should be encouraged. Also the compassionate and the off-label settings should be exploited to generate new evidence, and flexible regulatory innovations such as adaptive licensing could convey new agents early to rare cancer patients, while generating evidence. Though validation of surrogate end points is problematic in rare cancers, the use of an updated notion of tumor response may be of great value in the single patient to optimize the use of therapies, all the more the new ones. Disease-based communities, involving clinicians and patients, should be regularly consulted by regulatory bodies when setting their policies on drug approval and reimbursement in specific rare cancers .
The objective of this study is to compare image quality and lesion detection for full field digital mammography (FFDM) and film-screen mammography (FSM). In 200 women we performed digital mammography of one breast and film-screen mammography of the other breast. Imaging parameters were set automatically. Image quality, visualization of calcifications and masses were rated by three readers independently. Mean glandular dose was calculated for both systems. We found no significant difference in mean glandular dose. Image quality was rated by reader A/B/C as excellent for FFDM in 153/155/167 cases and for FSM in 139/116/114 cases (p<0.03/0.001/0.001). Microcalcifications were detected by FFDM in 103/89/98 and by FSM in 76/76/76 cases (p<0.01/0.06/0.01). Detection of masses did not differ significantly. FFDM provided significantly better visibility of skin and nipple-areola region (p<0.01). FFDM demonstrated improved image quality compared with film-screen mammography. Microcalcification detection was also significantly better with the digital mammography system for two of the three readers.
MT effects in human Achilles tendons can be reliably assessed in-vivo using a 3D UTE sequence at 3 T. All healthy tendons showed similar MTR values (coefficient of variation 10.0 ± 1.2 %). The examined patient showed a clearly different MT effect revealing a changed microstructure in the case of tendinopathy.
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