The Proportion of Women Who Have a Breast 4 Years after Breast Cancer Surgery: A Population-Based Cohort Study.

BACKGROUND: There are numerous pathways in breast cancer treatment, many of which enable women to retain a breast after treatment. We evaluated the proportion of women who have a breast, either through conserving surgery (BCS) or reconstruction, at 4-years after diagnosis, and how this varied by patient group. METHODS AND FINDINGS: We identified women with breast cancer who underwent initial BCS or mastectomy in English National Health Service (NHS) hospitals between January 2008 and December 2009 using the Hospital Episode Statistics (HES) database. Women were assigned into one of four patient groups depending on their age at diagnosis and presence of comorbidities. The series of breast cancer procedure (BCS, mastectomy, immediate, or delayed reconstruction) undergone by each women was identified over four years, and the proportion of women with a breast calculated. Variation was examined across patient groups, and English Cancer Networks. Between 2008 and 2009, 60,959 women underwent BCS or mastectomy. The proportion with a breast at 4 years was 79.3%, and 64.0%, in women less than 70 years without, and with comorbidities. Whilst in women aged 70 and over without, and with comorbidities, proportions were 52.6%, and 38.2%, respectively. Comorbidities were associated with lower proportions of BCS, but had little effect on reconstruction rates unlike age. Networks variation of 15% or more was found within each patient group, and Cancer Networks tended to have either a high or low proportion across all four patient groups. However, while 14% of women under 70 years had undergone reconstruction, less than 2% of women aged 70 or more had this treatment option. CONCLUSION: The proportion of women diagnosed with breast cancer who retain a breast at 4 years is strongly associated with age, and presence of comorbidities. There was significant variation between Cancer Networks indicating that women's experience in England was dependent on their geographical location of treatment

Impact of a Multifaceted Early Mobility Intervention for Critically Ill Children - the PICU Up! Trial: Study Protocol for a Multicenter Stepped-Wedge Cluster Randomized Controlled Trial

BACKGROUND: Over 50% of all critically ill children develop preventable intensive care unit-acquired morbidity. Early and progressive mobility is associated with improved outcomes in critically ill adults including shortened duration of mechanical ventilation and improved muscle strength. However, the clinical effectiveness of early and progressive mobility in the pediatric intensive care unit has never been rigorously studied. The objective of the study is to evaluate if the PICU Up! intervention, delivered in real-world conditions, decreases mechanical ventilation duration (primary outcome) and improves delirium and functional status compared to usual care in critically ill children. Additionally, the study aims to identify factors associated with reliable PICU Up! delivery. METHODS: The PICU Up! trial is a stepped-wedge, cluster-randomized trial of a pragmatic, interprofessional, and multifaceted early mobility intervention (PICU Up!) conducted in 10 pediatric intensive care units (PICUs). The trial\u27s primary outcome is days alive free of mechanical ventilation (through day 21). Secondary outcomes include days alive and delirium- and coma-free (ADCF), days alive and coma-free (ACF), days alive, as well as functional status at the earlier of PICU discharge or day 21. Over a 2-year period, data will be collected on 1,440 PICU patients. The study includes an embedded process evaluation to identify factors associated with reliable PICU Up! delivery. DISCUSSION: This study will examine whether a multifaceted strategy to optimize early mobility affects the duration of mechanical ventilation, delirium incidence, and functional outcomes in critically ill children. This study will provide new and important evidence on ways to optimize short and long-term outcomes for pediatric patients. TRIAL REGISTRATION: ClinicalTrials.gov NCT04989790. Registered on August 4, 2021

Age-related decline of peripheral visual processing: the role of eye movements

Earlier work suggests that the area of space from which useful visual information can be extracted (useful field of view, UFoV) shrinks in old age. We investigated whether this shrinkage, documented previously with a visual search task, extends to a bimanual tracking task. Young and elderly subjects executed two concurrent tracking tasks with their right and left arms. The separation between tracking displays varied from 3 to 35 cm. Subjects were asked to fixate straight ahead (condition FIX) or were free to move their eyes (condition FREE). Eye position was registered. In FREE, young subjects tracked equally well at all display separations. Elderly subjects produced higher tracking errors, and the difference between age groups increased with display separation. Eye movements were comparable across age groups. In FIX, elderly and young subjects tracked less well at large display separations. Seniors again produced higher tracking errors in FIX, but the difference between age groups did not increase reliably with display separation. However, older subjects produced a substantial number of illicit saccades, and when the effect of those saccades was factored out, the difference between young and older subjects’ tracking did increase significantly with display separation in FIX. We conclude that the age-related shrinkage of UFoV, previously documented with a visual search task, is observable with a manual tracking task as well. Older subjects seem to partly compensate their deficit by illicit saccades. Since the deficit is similar in both conditions, it may be located downstream from the convergence of retinal and oculomotor signals

Asthma and COPD in cystic fibrosis intron-8 5T carriers. A population-based study

BACKGROUND: Carriers of cystic fibrosis intron-8 5T alleles with high exon-9 skipping could have increased annual lung function decline and increased risk for asthma or chronic obstructive pulmonary disease (COPD). METHODS: We genotyped 9131 individuals from the adult Danish population for cystic fibrosis 5T, 7T, 9T, and F508del alleles, and examined associations between 11 different genotype combinations, and annual FEV(1 )decline and risk of asthma or COPD. RESULTS: 5T heterozygotes vs. 7T homozygous controls had no increase in annual FEV(1 )decline, self-reported asthma, spirometry-defined COPD, or incidence of hospitalization from asthma or COPD. In 5T/7T heterozygotes vs. 7T homozygous controls we had 90% power to detect an increase in FEV(1 )decline of 8 ml, an odds ratio for self-reported asthma and spirometry-defined COPD of 1.9 and 1.7, and a hazard ratio for asthma and COPD hospitalization of 1.8 and 1.6, respectively. Both 5T homozygotes identified in the study showed evidence of asthma, while none of four 5T/F508del compound heterozygotes had severe pulmonary disease. 7T/9T individuals had annual decline in FEV(1 )of 19 ml compared with 21 ml in 7T homozygous controls (t-test:P = 0.03). 6.7% of 7T homozygotes without an F508del allele in the cystic fibrosis transmembrane conductance regulator gene reported asthma vs. 11% of 7T/9T individuals with an F508del allele (χ(2):P = 0.01) and 40% of 7T homozygotes with an F508del allele (P = 0.04). 7T homozygotes with vs. without an F508del allele also had higher incidence of asthma hospitalization (log-rank:P = 0.003); unadjusted and adjusted equivalent hazard ratios for asthma hospitalization were 11 (95%CI:1.5–78) and 6.3 (0.84–47) in 7T homozygotes with vs. without an F508del allele. CONCLUSION: Polythymidine 5T heterozygosity is not associated with pulmonary dysfunction or disease in the adult Caucasian population. Furthermore, our results support that F508del heterozygosity is associated with increased asthma risk independently of the 5T allele

Monkey Steering Responses Reveal Rapid Visual-Motor Feedback

The neural mechanisms underlying primate locomotion are largely unknown. While behavioral and theoretical work has provided a number of ideas of how navigation is controlled, progress will require direct physiolgical tests of the underlying mechanisms. In turn, this will require development of appropriate animal models. We trained three monkeys to track a moving visual target in a simple virtual environment, using a joystick to control their direction. The monkeys learned to quickly and accurately turn to the target, and their steering behavior was quite stereotyped and reliable. Monkeys typically responded to abrupt steps of target direction with a biphasic steering movement, exhibiting modest but transient overshoot. Response latencies averaged approximately 300 ms, and monkeys were typically back on target after about 1 s. We also exploited the variability of responses about the mean to explore the time-course of correlation between target direction and steering response. This analysis revealed a broad peak of correlation spanning approximately 400 ms in the recent past, during which steering errors provoke a compensatory response. This suggests a continuous, visual-motor loop controls steering behavior, even during the epoch surrounding transient inputs. Many results from the human literature also suggest that steering is controlled by such a closed loop. The similarity of our results to those in humans suggests the monkey is a very good animal model for human visually guided steering