Integration of patient-reported outcome measures with key clinical outcomes after immediate latissimus dorsi breast reconstruction and adjuvant treatment

Background: linical evidence on patient-reported outcome measures (PROMS) in breast reconstruction is lacking. The aim of this study was to evaluate PROMs in implant-assisted latissimus dorsi (LDI) or tissue-only autologous latissimus dorsi (ALD) flap reconstruction in relation to complications and adjuvant treatments.Methods: this was a prospective cohort study involving six UK centres. Eligible patients had primary early-stage breast cancer. The European Organization for Research and Treatment of Cancer quality-of-life questionnaire (QLQ)-C30 and QLQ-BR23, Functional Assessment of Cancer Therapy—Breast Cancer scale (FACT-B), Body Image Scale, and Hospital Anxiety and Depression Scale were completed before operation and at 3, 6 and 12 months after surgery.Results: a total of 182 patients (82 LDI and 100 ALD) were recruited between 2007 and 2010 with symptomatic (59·9 per cent) or screen-detected (39·6 per cent) cancers. Some 64·3 per cent had lymph node-negative disease; 30 per cent of the LDI group had radiotherapy, compared with 53·0 per cent in the ALD group (P = 0·004). Early complications up to 3 months after surgery were reported in 66 and 51·0 per cent of patients in the LDI and ALD groups respectively (P = 0·062) and long-term complications (4–12 months) in 48 and 45·0 per cent (P = 0·845). Role functioning and pain (P = 0·002 for both) were adversely affected in the ALD group compared with results in the LDI group, with no significant effects of radiotherapy on any health-related quality of life (HRQL). Chemotherapy and early complications adversely affected HRQL, which improved between 3 and 12 months after surgery (P < 0·010 for all).Conclusion: there is evidence of similar HRQL between types of latissimus dorsi breast reconstruction for up to a year after surgery. There appear to be no overarching effects for radiotherapy after mastectomy on the specific HRQL domains studied in the short term. The identification of variables that affect HRQL is important, including their integration into the analysis of PROM

Mistimed malaria parasites re‐synchronise with host feeding‐fasting rhythms by shortening the duration of intra‐erythrocytic development

AIMS: Malaria parasites exhibit daily rhythms in the intra‐erythrocytic development cycle (IDC) that underpins asexual replication in the blood. The IDC schedule is aligned with the timing of host feeding‐fasting rhythms. When the IDC schedule is perturbed to become mismatched to host rhythms, it readily reschedules but it is not known how. METHODS: We intensively follow four groups of infections that have different temporal alignments between host rhythms and the IDC schedule for 10 days, before and after the peak in asexual densities. We compare how the duration, synchrony and timing of the IDC differs between parasites in control infections and those forced to reschedule by 12 hours and ask whether the density of parasites affects the rescheduling process. RESULTS AND CONCLUSIONS: Our experiments reveal parasites shorten the IDC duration by 2–3 hours to become realigned to host feeding‐fasting rhythms with 5–6 days, in a density‐independent manner. Furthermore, parasites are able to reschedule without significant fitness costs for them or their hosts. Understanding the extent of, and limits on, plasticity in the IDC schedule may reveal targets for novel interventions, such as drugs to disrupt IDC regulation and preventing IDC dormancy conferring tolerance to existing drugs

Stress, drugs and the evolution of reproductive restraint in malaria parasites

Life-history theory predicts that sexually reproducing organisms have evolved to resolve resource-allocation trade-offs between growth/survival versus reproduction, and current versus future reproduction. Malaria parasites replicate asexually in their vertebrate hosts, but must reproduce sexually to infect vectors and be transmitted to new hosts. As different specialized stages are required for these functions, the division of resources between these life-history components is a fundamental evolutionary problem. Here, we test how drug-sensitive and drug-resistant isolates of the human malaria parasite Plasmodium falciparum resolve the trade-off between in-host replication and between-host transmission when exposed to treatment with anti-malarial drugs. Previous studies have shown that parasites increase their investment in sexual stages when exposed to stressful conditions, such as drugs. However, we demonstrate that sensitive parasites facultatively decrease their investment in sexual stages when exposed to drugs. In contrast to previous studies, we tested parasites from a region where treatment with anti-malarial drugs is common and transmission is seasonal. We hypothesize that when exposed to drugs, parasites invest in their survival and future transmission by diverting resources from reproduction to replication. Furthermore, as drug-resistant parasites did not adjust their investment when exposed to drugs, we suggest that parasites respond to changes in their proliferation (state) rather the presence of drugs

Sib-mating does not lead to facultative sex ratio adjustment in the parasitoid wasp, Nasonia vitripennis

Sex ratio theory predicts that in haplodiploid species, females should lay a relatively more female-biased offspring sex ratio when they mate with a sibling compared with when they mate with a non-relative. This is because in haplodiploids, inbreeding leads to females having greater relatedness to daughters relative to sons. This prediction has only been tested in the parasitoid waspNasonia vitripennis, where no support for this prediction was found. However, a limitation of this previous work is that it was carried out with only two females laying eggs per patch. This is a problem, because in this case the predicted difference in the offspring sex ratio is small and therefore hard to detect. We addressed this problem by utilizing a situation in which larger sex ratio differences are predicted – five females laying eggs per patch. Consistent with the previous results, we also found that the offspring sex ratio laid by a female was not influenced by whether she mated with a sibling or non-relative. Meta-analysis of all the experiments we have undertaken confirms this pattern. This failure to respond to the identity of a mating partner suggests females are unable to discriminate kin and is a relatively rare example of maladaptive sex allocation

One Change, Different Effects: The Impacts of Reducing Clerkship Length

Background: Medical school curricula are constantly evolving and change has potential positive and negative effects. At East Tennessee State University Quillen College of Medicine, a broader understanding of the effects of a curriculum change (reduction in clerkship length for one transitional year) was explored. Methods: A broad, system-wide evaluation was used to evaluate impacts on all stakeholders. Curriculum management data, including qualitative and quantitative data and short-term and follow-up perspectives of stakeholders, were used for evaluation. Results: Students evaluated the change positively. Academic performance in the transitional year was similar to the prior year. Differences in students’ clerkship evaluations were not statistically significant. Clerkship directors were concerned that students’ clinical experience suffered and noted that implementing changes was time consuming but recognized the benefits for students. Administrators dedicated a significant amount of time to planning the transitional year; however, the additional weeks at the beginning of fourth year made the scheduling process easier. Conclusion: This article demonstrates an overall positive result with this tool for curriculum change but also indicates the impacts differed across stakeholders. Knowledge gained from this experience can help other schools successfully anticipate challenges and prepare for a variety of outcomes in implementing necessary curriculum change

Modeling How Shoreline Shape Affects Tides and How Underwater Structures Attenuate Wave Energy: An Example of the Georgia Bight

Two demonstrations are presented that lead students to a greater understanding of ocean tides and wave energy, using the unique tidal range and wave action of the Georgia Bight as an example. The goal is to explain how varying geological features in coastal regions create different wave energies and how the shape of a coastline affects the magnitude of the tidal range. These mechanisms were demonstrated to students in an upper-division college course prior to attending a field trip, in which they would evaluate real-world examples of coastlines with high and low wave energy, and regions with large and small tidal magnitudes. Here, the method of applied learning proved to be successful in guiding students to better comprehension of concepts when relating demonstrations to firsthand observations in the field

Monitoring young associations and open clusters with Kepler in two-wheel mode

We outline a proposal to use the Kepler spacecraft in two-wheel mode to monitor a handful of young associations and open clusters, for a few weeks each. Judging from the experience of similar projects using ground-based telescopes and the CoRoT spacecraft, this program would transform our understanding of early stellar evolution through the study of pulsations, rotation, activity, the detection and characterisation of eclipsing binaries, and the possible detection of transiting exoplanets. Importantly, Kepler's wide field-of-view would enable key spatially extended, nearby regions to be monitored in their entirety for the first time, and the proposed observations would exploit unique synergies with the GAIA ESO spectroscopic survey and, in the longer term, the GAIA mission itself. We also outline possible strategies for optimising the photometric performance of Kepler in two-wheel mode by modelling pixel sensitivity variations and other systematics.Comment: 10 pages, 6 figures, white paper submitted in response to NASA call for community input for alternative science investigations for the Kepler spacecraf