Complex cognitive algorithms preserved by selective social learning in experimental populations.

Many human abilities rely on cognitive algorithms discovered by previous generations. Cultural accumulation of innovative algorithms is hard to explain because complex concepts are difficult to pass on. We found that selective social learning preserved rare discoveries of exceptional algorithms in a large experimental simulation of cultural evolution. Participants (N = 3450) faced a difficult sequential decision problem (sorting an unknown sequence of numbers) and transmitted solutions across 12 generations in 20 populations. Several known sorting algorithms were discovered. Complex algorithms persisted when participants could choose who to learn from but frequently became extinct in populations lacking this selection process, converging on highly transmissible lower-performance algorithms. These results provide experimental evidence for hypothesized links between sociality and cognitive function in humans.

Developing Healthcare Team Observations for Patient Safety (HTOPS): senior medical students capture everyday clinical moments.

BACKGROUND: Aviation has used a real-time observation method to advance anonymised feedback to the front-line and improve safe practice. Using an experiential learning method, this pilot study aimed to develop an observation-based real-time learning tool for final-year medical students with potential wider use in clinical practice. METHODS: Using participatory action research, we collected data on medical students' observations of real-time clinical practice. The observation data was analysed thematically and shared with a steering group of experts to agree a framework for recording observations. A sample of students (observers) and front-line clinical staff (observed) completed one-to-one interviews on their experiences. The interviews were analysed using thematic analysis. RESULTS: Thirty-seven medical students identified 917 issues in wards, theatres and clinics in an acute hospital trust. These issues were grouped into the themes of human influences, work environment and systems. Aviation approaches were adapted to develop an app capable of recording real-time positive and negative clinical incidents. Five students and eleven clinical staff were interviewed and shared their views on the value of a process that helped them learn and has the potential to advance the quality of practice. Concerns were shared about how the observational process is managed. CONCLUSION: The study developed an app (Healthcare Team Observations for Patient Safety-HTOPS), for recording good and poor clinical individual and team behaviour in acute-care practice. The process advanced medical student learning about patient safety. The tool can identify the totality of patient safety practice and illuminate strength and weakness. HTOPS offers the opportunity for collective ownership of safety concerns without blame and has been positively received by all stakeholders. The next steps will further refine the app for use in all clinical areas for capturing light noise.

Major Urological Cancer Surgery for Patients is Safe and Surgical Training Should Be Encouraged During the COVID-19 Pandemic: A Multicentre Analysis of 30-day Outcomes.

COVID-19 has resulted in the deferral of major surgery for genitourinary (GU) cancers with the exception of cancers with a high risk of progression. We report outcomes for major GU cancer operations, namely radical prostatectomy (RP), radical cystectomy (RC), radical nephrectomy (RN), partial nephrectomy (PN), and nephroureterectomy performed at 13 major GU cancer centres across the UK between March 1 and May 5, 2020. A total of 598 such operations were performed. Four patients (0.7%) developed COVID-19 postoperatively. There was no COVID-19-related mortality at 30 d. A minimally invasive approach was used in 499 cases (83.4%). A total of 228 cases (38.1%) were described as training procedures. Training case status was not associated with a higher American Society of Anesthesiologists (ASA) score (p = 0.194) or hospital length of stay (LOS; p > 0.05 for all operation types). The risk of contracting COVID-19 was not associated with longer hospital LOS (p = 0.146), training case status (p = 0.588), higher ASA score (p = 0.295), or type of hospital site (p = 0.303). Our results suggest that major surgery for urological cancers remains safe and training should be encouraged during the ongoing COVID-19 pandemic provided appropriate countermeasures are taken. These real-life data are important for policy-makers and clinicians when counselling patients during the current pandemic. PATIENT SUMMARY: We collected outcome data for major operations for prostate, bladder, and kidney cancers during the COVID-19 pandemic. These surgeries remain safe and training should be encouraged during the ongoing pandemic provided appropriate countermeasures are taken. Our real-life results are important for policy-makers and clinicians when counselling patients during the COVID-19 pandemic.

The British Association of Dermatologists' Undergraduate Curriculum Update 2021.

The General Medical Council (GMC) plans to introduce a national Medical Licensing Assessment (MLA) in 2024 for all UK medical students as part of their primary medical qualification, with dermatology specified in its assessment blueprint. We present an Update to the British Association of Dermatologists' Undergraduate Curriculum, aligned both to the MLA Content Map and the GMC Outcomes for Graduates 2018.

Distinctive clinical and histological characteristics of atrophic and hypertrophic facial photoageing.

BACKGROUND: Photoageing describes complex cutaneous changes which occur following chronic exposure to solar ultraviolet radiation (UVR). Amongst White Northern Europeans, facial photoageing appears as distinct clinical phenotypes: 'hypertrophic' photoageing (HP) and 'atrophic' photoageing (AP). Deep, coarse wrinkles predominate in individuals with HP, whereas those with AP have relatively smooth, unwrinkled skin with pronounced telangiectasia. AP individuals have an increased propensity for developing keratinocyte cancers. OBJECTIVES: To investigate whether histological differences underlie these distinct phenotypes of facial photoageing. METHODS: Facial skin biopsies were obtained from participants with AP (10 M, 10 F; mean age: 78.7 years) or HP (10 M, 10 F; mean age: 74.5 years) and were assessed histologically and by immunohistochemistry. RESULTS: Demographic characterization revealed 95% of AP subjects, as compared to 35% with HP, were Fitzpatrick skin type I/II; of these, 50% had a history of one or more keratinocyte cancers. There was no history of keratinocyte cancers in the HP cohort. Analysis of UVR-induced mitochondrial DNA damage confirmed that all volunteers had received similar lifetime cumulative doses of sun exposure. Histologically, male AP had a significantly thicker epidermis than did AP females or those of either sex with HP. HP facial skin exhibited severe solar elastosis, whereas in AP facial skin, solar elastosis was apparent only in females. Loss of papillary dermal fibrillin-rich microfibrils occurred in all HP and AP female subjects, but not in AP males. Furthermore, male AP had a significant reduction in collagen VII at the dermal-epidermal junction than did AP females or those of either sex with HP. CONCLUSIONS: This study provides further evidence that AP and HP represent distinct clinical and histological entities. Knowledge of these two phenotypes is clinically relevant due to the increased prevalence of keratinocyte cancers in those - particularly males - with the AP phenotype.

Next steps in dermatology training: choosing to enter higher speciality training and the transition from trainee to consultant dermatologist.

BACKGROUND: Junior doctors are required to make career decisions at an early stage in their postgraduate training. Trainees also feel inadequately prepared for the transition to consultant roles. AIM: To explore the key factors influencing the choice of dermatology as a postgraduate medical career and to identify the training needs required for transition from trainee to consultant. METHODS: An online questionnaire was designed to identify (i) why trainees chose a postgraduate medical career in dermatology, and (ii) the training required for transition from trainee to consultant. RESULTS: In total, 46 responses were received from trainees in their first to final years (ST3-6), of whom 89% had undertaken an undergraduate dermatology placement, with a median duration of 2 weeks. Dermatology was considered as a career during medical school by 61% of trainees, and 41% confirmed their decision to pursue a career in dermatology during foundation training. The most influential factors involved in speciality selection were first, enjoyment of the work, second, postgraduate experience and equal third, the variety of the speciality and the regularity of working hours (P < 0.05). Mentoring was pivotal to career decision-making. Significant numbers of trainees expressed a need for training in medical leadership, such as running an outpatient clinic and supervising clinical multidisciplinary teams. Although larger numbers of trainees had training in management of dermatology services, such as service improvement (52%) and local governance/National Health Service structures (43%), significant numbers of trainees had no training in writing job plans (89%) or business plans (85%). Training was significantly deficient for personal management and self-awareness. CONCLUSION: Our study highlights important considerations in career decision-making for trainees. Training in medical leadership, management and self-awareness could be enhanced to ensure that trainees feel adequately equipped for consultant roles.

Surgeon-Team Separation in Robotic Theaters: A Qualitative Observational and Interview Study.

BACKGROUND: The rapid uptake of robotic surgery has largely been driven by the improved technical aspects of minimally invasive surgery including improved ergonomics, wristed instruments, and 3-dimensional vision. However, little attention has been given to the effect of physical separation of the surgeon from the rest of the operating team. PURPOSE: The aim of this study was to examine in depth how this separation affected team dynamics and staff emotions. METHODS: Robotic procedures were observed in 2 tertiary hospitals, and laparoscopic/open procedures were added for comparison; field notes were taken instantaneously. One-to-one interviews with theater team members were audio recorded and transcribed verbatim. Qualitative analysis was conducted via grounded theory approach using NVIVO11. RESULTS: Twenty-nine participants (26 interviewed) were recruited to the study (11 females) and 134 (109 robotic) hours of observation were completed across gynecology, urology, and colorectal surgery.The following 3 main themes emerged with compounding factors identified: (a) communication challenge, (b) immersion versus distraction, and (c) emotional impact. Compounding factors included the following: individual and team experience, staffing levels, and the physical theater environment. CONCLUSIONS: Our emergent theory is that "surgeon-team separation in robotic theaters poses communication challenges which impacts on situational awareness and staff emotions." These can be ameliorated by staff training, increased experience, and team/procedure consistency.

Paediatric nurses' adoption of aseptic non-touch technique.

BACKGROUND:: in 2015, NHS Wales introduced a national standardised approach to aseptic non-touch technique (ANTT). This approach aims to standardise practice and promote better clinical outcomes. AIM:: to provide insight into the challenges faced by clinical staff adopting ANTT during intravenous therapy. METHODS:: focused ethnography across two paediatric wards in NHS Wales. Data collection included participant observation, audit questionnaires and semi-structured interviews. Data were analysed according to Wolcott's (1994) process and emerging themes were reflected upon against the theoretical framework of Kirkpatrick's (1994) model of training evaluation. FINDINGS:: absence of feedback following training, individual preference, lack of opportunity to practise the ANTT technique, lack of clarity and standardisation and expectations of parents/medical staff are all challenges faced by registered nurses. IMPLICATIONS OF THE STUDY:: the findings may be used by NHS managers to support national initiatives within staff training and development programmes, and to improve infection prevention initiatives. Organisational culture is a modifier of healthcare worker behaviour and requires further attention locally and nationally. Quality assurance in the adoption of standardised best practice must take into account staff training and development needs, and workplace culture.

Radiofrequency-induced Thermo-chemotherapy Effect Versus a Second Course of Bacillus Calmette-Guérin or Institutional Standard in Patients with Recurrence of Non-muscle-invasive Bladder Cancer Following Induction or Maintenance Bacillus Calmette-Guérin Therapy (HYMN): A Phase III, Open-label, Randomised Controlled Trial.

BACKGROUND: There is no effective intravesical second-line therapy for non-muscle-invasive bladder cancer (NMIBC) when bacillus Calmette-Guérin (BCG) fails. OBJECTIVE: To compare disease-free survival time (DFS) between radiofrequency-induced thermo-chemotherapy effect (RITE) and institutional standard second-line therapy (control) in NMIBC patients with recurrence following induction/maintenance BCG. DESIGN, SETTINGS, AND PARTICIPANTS: Open-label, phase III randomised controlled trial accrued across 14 centres between May 2010 and July 2013 (HYMN [ClinicalTrials.gov: NCT01094964]). INTERVENTION: Patients were randomly assigned (1:1) to RITE (60min, 40mg mitomycin-C, 42±2°C) or control following stratification for carcinoma in situ (CIS) status (present/absent), therapy history (failure of previous induction/maintenance BCG), and treatment centre. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: Primary outcome measures were DFS and complete response (CR) at 3 mo for the CIS at randomisation subgroup. Analysis was based on intention-to-treat. RESULTS AND LIMITATIONS: A total of 104 patients were randomised (48 RITE: 56 control). Median follow-up for the 31 patients without a DFS event was 36 mo. There was no significant difference in DFS between treatment arms (hazard ratio [HR] 1.33, 95% confidence interval [CI] 0.84-2.10, p=0.23) or in 3-mo CR rate in CIS patients (n=71; RITE: 30% vs control: 47%, p=0.15). There was no significant difference in DFS between treatment arms in non-CIS patients (n=33; RITE: 53% vs control: 24% at 24 mo, HR 0.50, 95% CI 0.22-1.17, p=0.11). DFS was significantly lower in RITE than in control in CIS with/without papillary patients (n=71; HR 2.06, 95% CI 1.17-3.62, p=0.01; treatment-subgroup interaction p=0.007). Disease progression was observed in four patients in each treatment arm. Adverse events and health-related quality of life between treatment arms were comparable. CONCLUSIONS: DFS was similar between RITE and control. RITE may be a second-line therapy for non-CIS recurrence following BCG failure; however, confirmatory trials are needed. RITE patients with CIS with/without papillary had lower DFS than control. HYMN highlights the importance of the control arm when evaluating novel therapies. PATIENT SUMMARY: This study did not show a difference in bladder cancer outcomes between microwave-heated chemotherapy and standard of care treatment. Papillary bladder lesions may benefit from microwave-heated chemotherapy treatment; however, more research is needed. Both treatments are similarly well tolerated.

Structure evolution of h.c.p./c.c.p. metal oxide interfaces in solid-state reactions.

The structure of crystalline interfaces plays an important role in solid-state reactions. The Al2O3/MgAl2O4/MgO system provides an ideal model system for investigating the mechanisms underlying the migration of interfaces during interface reaction. MgAl2O4 layers have been grown between Al2O3 and MgO, and the atomic structure of Al2O3/MgAl2O4 interfaces at different growth stages was characterized using aberration-corrected scanning transmission electron microscopy. The oxygen sublattice transforms from hexagonal close-packed (h.c.p.) stacking in Al2O3 to cubic close-packed (c.c.p.) stacking in MgAl2O4. Partial dislocations associated with steps are observed at the interface. At the reaction-controlled early growth stages, such partial dislocations coexist with the edge dislocations. However, at the diffusion-controlled late growth stages, such partial dislocations are dominant. The observed structures indicate that progression of the Al2O3/MgAl2O4 interface into Al2O3 is accomplished by the glide of partial dislocations accompanied by the exchange of Al3+ and Mg2+ cations. The interface migration may be envisaged as a plane-by-plane zipper-like motion, which repeats along the interface facilitating its propagation. MgAl2O4 grains can adopt two crystallographic orientations with a twinning orientation relationship, and grow by dislocations gliding in opposite directions. Where the oppositely propagating partial dislocations and interface steps meet, interlinked twin boundaries and incoherent Σ3 grain boundaries form. The newly grown MgAl2O4 grains compete with each other, leading to a growth selection and successive coarsening of the MgAl2O4 grains. This understanding could help to interpret the interface reaction or phase transformation of a wide range of materials that exhibit a similar h.c.p./c.c.p. transition.

A photonumeric scale for the assessment of atrophic facial photodamage.

BACKGROUND: Photonumeric scales have consistently shown superiority over descriptive equivalents. They have the advantage of providing a consistent visual frame of reference by minimizing variability in perception and subjectivity. A photonumeric scale to assess hypertrophic facial photodamage already exists. However, there is currently no objective measure for atrophic facial photodamage. To address this, we have devised a nine-point photonumeric standardized scale. OBJECTIVES: To design, test and validate a photonumeric scale for the assessment of atrophic facial photodamage against a descriptive scale for the same indication. METHODS: A pool of 393 facial photographs (en face and 45° oblique) from 131 individuals with atrophic facial photodamage was created. Five photographic standards were selected and assigned grades zero through to eight, where zero is no photodamage and eight is severe atrophic photodamage, thus making a nine-point scale. Twenty photographs spanning the entire range of values were selected to test the scale. Testing was performed alongside a descriptive equivalent. A panel of 10 dermatologists, 10 nondermatology clinicians and 14 dermatology scientists marked the two scales; marking was repeated 1 week later. RESULTS: There was a significantly greater agreement between the graders using the photonumeric scale than the descriptive scale (kappa values 0·71 and 0·37 with standardized errors of 0·57 and 0·17, respectively) with no significant difference in repeatability between the two methods (P < 0·05). CONCLUSIONS: The study describes a new photonumeric scale for atrophic photodamage. This would be a useful adjunct in both the clinical and research settings.

Evidence for causal top-down frontal contributions to predictive processes in speech perception.

Perception relies on the integration of sensory information and prior expectations. Here we show that selective neurodegeneration of human frontal speech regions results in delayed reconciliation of predictions in temporal cortex. These temporal regions were not atrophic, displayed normal evoked magnetic and electrical power, and preserved neural sensitivity to manipulations of sensory detail. Frontal neurodegeneration does not prevent the perceptual effects of contextual information; instead, prior expectations are applied inflexibly. The precision of predictions correlates with beta power, in line with theoretical models of the neural instantiation of predictive coding. Fronto-temporal interactions are enhanced while participants reconcile prior predictions with degraded sensory signals. Excessively precise predictions can explain several challenging phenomena in frontal aphasias, including agrammatism and subjective difficulties with speech perception. This work demonstrates that higher-level frontal mechanisms for cognitive and behavioural flexibility make a causal functional contribution to the hierarchical generative models underlying speech perception.

Timely initiation of chemotherapy: a systematic literature review of six priority cancers - results and recommendations for clinical practice.

This review evaluated the association between time-to-chemotherapy (TTC) and survival in six priority cancers. A systematic review of the literature was undertaken for papers indexed in the MEDLINE and Cochrane Library databases from the earliest index until April 2014. The methodology used has been published in a separate paper (Guidelines for timely initiation of chemotherapy: a proposed framework for access to medical oncology and haematology cancer clinics and chemotherapy services). The optimal timing of chemotherapy in breast cancer is unclear as available studies are of low quality, report inconsistent results and are limited to the adjuvant setting. However, increased TTC may have a negative prognostic impact, and delays beyond 4 weeks should be avoided. Studies suggest that the optimal timing for initiation of adjuvant chemotherapy for surgically resected colorectal cancer is 4-8 weeks post-surgery. Timing of chemotherapy for metastatic colorectal cancer does not influence survival. There is a paucity of studies to guide the timing of chemotherapy for the treatment of lymphoma and myeloma; no definitive conclusions can be drawn, and clinician discretion should be applied. The optimal timing of chemotherapy in lung cancer is unclear; however, rapid tumour growth and poor disease prognosis suggest that delays should be avoided wherever possible. The optimal timing of chemotherapy in ovarian cancer is unclear as available studies are of low level, report inconsistent results and are limited to the post-surgery setting; however, increased TTC may have a negative prognostic impact; therefore, delays beyond 4 weeks should be avoided.

Biology of the eyelash hair follicle: an enigma in plain sight.

Because of their crucial impact on our perception of beauty, eyelashes constitute a prime target for the cosmetic industry. However, when compared with other hair shafts and the mini-organs that produce them [eyelash hair follicles (ELHFs)], knowledge on the biology underlying growth and pigmentation of eyelashes is still rudimentary. This is due in part to the extremely restricted availability of human ELHFs for experimental study, underappreciation of their important sensory and protective functions and insufficient interest in understanding why they are distinct from scalp hair follicles (HFs) (e.g. ELHFs produce shorter hair shafts, do not possess an arrector pili muscle, have a shorter hair cycle and undergo greying significantly later than scalp HFs). Here we synthesize the limited current knowledge on the biology of ELHFs, in humans and other species, their role in health and disease, the known similarities with and differences from other HF populations, and their intrinsic interethnic variations. We define major open questions in the biology of these intriguing mini-organs and conclude by proposing future research directions. These include dissecting the molecular and cellular mechanisms that underlie trichomegaly and the development of in vitro models in order to interrogate the distinct molecular controls of ELHF growth, cycling and pigmentation and to probe novel strategies for the therapeutic and cosmetic manipulation of ELHFs beyond prostaglandin receptor stimulation.

Is Immediate Radical Cystectomy Necessary for All Patients with Non-Muscle-Invasive Micropapillary Bladder Cancer?

INTRODUCTION: We aim to review the outcomes of micropapillary urothelial carcinoma (MPUC) of the bladder from a single institution. The hypothesis is that non-muscle-invasive (NMI) MPUC may have a heterogeneous prognosis, and detailed pathological analysis may identify patients that could be managed without immediate cystectomy. PATIENTS AND METHODS: This is a retrospective analysis of patients presenting with MPUC in a primary transurethral resection specimen (n = 40). The pattern of micropapillary (MP) differentiation [surface/non-invasive (sMP) or invasive (iMP)], extent of MP differentiation and lymphovascular invasion (LVI) were correlated with overall survival (OS), recurrence-free survival and upstaging at re-resection. RESULTS: Sixteen of 40 patients died after a median follow-up of 37 months. Tumour stage was strongly predictive of OS (p < 0.0001). LVI was associated with increased mortality (hazard ratio 12.4, 95% CI: 3.5-44.5, p = 0.0001), higher pathological stage (p = 0.001), lymph node involvement (p = 0.001) and iMP differentiation (p = 0.006). In NMI patients not undergoing cystectomy (n = 17), NMI-sMP compared with NMI-iMP differentiation was associated with an improved OS when compared with iMP (63 vs. 47 months, p = 0.05). CONCLUSIONS: MPUC is an aggressive variant of urothelial carcinoma (UC). Similar to conventional UC, LVI associated with MPUC is an adverse prognostic indicator. iMP is a morphological marker for LVI. Histopathological reports should distinguish between sMP and iMP differentiation.