Trichothiodystrophy (TTD) is a rare autosomal recessive disorder whose defining feature is brittle hair. Associated clinical symptoms include physical and mental retardation of different severity, ichthyosis, premature aging, and, in half of the patients, photosensitivity. Recently, C7orf11 (TTDN1) was identified as the first disease gene for the nonphotosensitive form of TTD, being mutated in two unrelated cases and in an Amish kindred. We have evaluated the involvement of TTDN1 in 44 unrelated nonphotosensitive TTD cases of different geographic origin and with different disease severity. Mutations were found in six patients, five of whom are homozygous and one of whom is a compound heterozygote. All five identified mutations are deletions that have not been described before. Three are deletions of a few bases, resulting in frameshifts and premature termination codons. The other two include the whole TTDN1 gene, suggesting that TTDN1 is not essential for cell proliferation and viability. The severity of the clinical features does not correlate with the type of mutation, indicating that other factors besides TTDN1 mutations influence the severity of the disorder. Since only a small proportion of the analyzed cases were mutated in TTDN1, the nonphotosensitive form of TTD is genetically heterogeneous. Mutations in TTDN1 do not affect the response to ultraviolet (UV) light or the steady state level of the repair/transcription factor IIH (TFIIH), which is central to the onset of the photosensitive form of TTD.
Radiotherapy is widely used in breast cancer treatment, particularly in patients undergoing breast conserving surgery, principally in order to reduce risk of local recurrence (Liljegren et al. 1999; Fisher et al. 2002). Although radiation therapy has been observed in a major metaanalysis to confer a net survival benefit (Clarke et al. 2005), it is not without side-effects. It has been observed to confer increased risks of cardiovascular events and lung tumours (Clarke et al. 2005; Darby et al. 2005). The fact that radiation therapy confers both benefits and harms raises issues pertinent to all treatments, i.e., the importance of selecting patient populations for which the balance of benefits to harms is optimised, and of excluding those patients who will not benefit from the treatment, or at least not sufficiently to outweigh the risk of adverse effects. Given the current lack of confidence that the prognostic indicators for such selection exist, conservative therapy includes post-surgical radiotherapy as a standard of care.
There is a need to research interventions that improve access to and convenience of breast cancer screening services. We conducted a randomised trial comparing invitations to out-of-hours appointments with standard office hour appointments. Women who were to be invited for routine breast screening were randomised (3 : 1 : 1 : 1) to one of these screening invitations: standard office hour appointment, office hour appointment with the option to change to an out-of-hours appointment, weekday evening appointment, or weekend appointment. A total of 9410 women were invited to an office hour, 3519 to an office hour with the option to change, 3271 to a weekday evening, and 3162 to a weekend appointment. The offer of an initial out-of-hours appointment was associated with a non-significant decrease in attendance rates (73.7% vs 74.1%). The highest attendance was observed in the group offered an initial office hour appointment with the option to change to out-of-hours (76.1% vs 73.3% for standard office hour, P=0.001), with 7% of invitees exercising the option to change. The optimum strategy for improving attendance at breast screening is to offer a traditional office hour appointment and including in the letter of invitation an option to change to an evening or weekend appointment if wished.
Current guidelines recommend endoscopic surveillance for Barrett oesophagus (BE), but the value of surveillance is still debated. Using a combination of primary care, secondary care and cancer registry datasets, we examined the impact of a prior BE diagnosis, clinical and risk factors on survival from oesophageal cancer and adenocarcinoma.
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