Bioarchaeology aids the cultural understanding of six characters in search of their agency (Tarquinia, ninth-seventh century BC, central Italy).

Etruria contained one of the great early urban civilisations in the Italian peninsula during the first millennium BC, much studied from a cultural, humanities-based, perspective, but relatively little with scientific data, and rarely in combination. We have addressed the unusual location of twenty inhumations found in the sacred heart of the Etruscan city of Tarquinia, focusing on six of these as illustrative, contrasting with the typical contemporary cremations found in cemeteries on the edge of the city. The cultural evidence suggests that the six skeletons were also distinctive in their ritualization and memorialisation. Focusing on the six, as a representative sample, the scientific evidence of osteoarchaeology, isotopic compositions, and ancient DNA has established that these appear to show mobility, diversity and violence through an integrated bioarchaeological approach. The combination of multiple lines of evidence makes major strides towards a deeper understanding of the role of these extraordinary individuals in the life of the early city of Etruria.

Multiproxy bioarchaeological data reveals interplay between growth, diet and population dynamics across the transition to farming in the central Mediterranean.

The transition to farming brought on a series of important changes in human society, lifestyle, diet and health. The human bioarchaeology of the agricultural transition has received much attention, however, relatively few studies have directly tested the interrelationship between individual lifestyle factors and their implications for understanding life history changes among the first farmers. We investigate the interplay between skeletal growth, diet, physical activity and population size across 30,000 years in the central Mediterranean through a 'big data' cross-analysis of osteological data related to stature (n = 361), body mass (n = 334) and long bone biomechanics (n = 481), carbon (δ13C) and nitrogen (δ15N) stable isotopes (n = 1986 human, n = 475 animal) and radiocarbon dates (n = 5263). We present the observed trends on a continuous timescale in order to avoid grouping our data into assigned 'time periods', thus achieving greater resolution and chronological control over our analysis. The results identify important changes in human life history strategies associated with the first farmers, but also highlight the long-term nature of these trends in the millennia either side of the agricultural transition. The integration of these different data is an important step towards disentangling the complex relationship between demography, diet and health, and reconstruct life history changes within a southern European context. We believe the methodological approach adopted here has broader global implications for bioarchaeological studies of human adaptation more generally.

Observation of Low-Lying Isomeric States in

We report on new measurements establishing the existence of low-lying isomeric states in ^{136}Cs using γ rays produced in ^{136}Xe(p,n)^{136}Cs reactions. Two states with O(100) ns lifetimes are placed in the decay sequence of the ^{136}Cs levels that are populated in charged-current interactions of solar neutrinos and fermionic dark matter with ^{136}Xe. Xenon-based experiments can therefore exploit a delayed-coincidence tag of these interactions, greatly suppressing backgrounds to enable spectroscopic studies of solar neutrinos and dark matter.

The PerPAIN trial: a pilot randomized controlled trial of personalized treatment allocation for chronic musculoskeletal pain-a protocol.

BACKGROUND: The therapy of chronic musculoskeletal pain (CMSP) is complex and the treatment results are often insufficient despite numerous therapeutic options. While individual patients respond very well to specific interventions, other patients show no improvement. Personalized treatment assignment offers a promising approach to improve response rates; however, there are no validated cross-disease allocation algorithms available for the treatment of chronic pain in validated personalized pain interventions. This trial aims to test the feasibility and safety of a personalized pain psychotherapy allocation with three different treatment modules and estimate initial signals of efficacy and utility of such an approach compared to non-personalized allocation. METHODS: This is a randomized, controlled assessor-blinded pilot trial with a multifactorial parallel arm design. CMSP patients (n = 105) will be randomly assigned 1:1 to personalized or non-personalized treatment based on a cluster assignment of the West Haven-Yale Multidimensional Pain Inventory (MPI). In the personalized assignment condition, patients with high levels of distress receive an emotional distress-tailored intervention, patients with pain-related interference receive an exposure/extinction-tailored treatment intervention and patients who adapt relatively well to the pain receive a low-level smartphone-based activity diary intervention. In the control arm, patients receive one of the two non-matching interventions. Effect sizes will be calculated for change in core pain outcome domains (pain intensity, physical and emotional functioning, stress experience, participant ratings of improvement and satisfaction) after intervention and at follow-up. Feasibility and safety outcomes will assess rates of recruitment, retention, adherence and adverse events. Additional data on neurobiological and psychological characteristics of the patients are collected to improve treatment allocation in future studies. CONCLUSION: Although the call for personalized treatment approaches is widely discussed, randomized controlled trials are lacking. As the personalization of treatment approaches is challenging, both allocation and intervention need to be dynamically coordinated. This study will test the feasibility and safety of a novel study design in order to provide a methodological framework for future multicentre RCTs for personalized pain psychotherapy. TRIAL REGISTRATION: German Clinical Trials Register, DRKS00022792 ( https://www.drks.de ). Prospectively registered on 04/06/2021.

Nosocomial or not? A combined epidemiological and genomic investigation to understand hospital-acquired COVID-19 infection on an elderly care ward.

BACKGROUND: COVID-19 has the potential to cause outbreaks in hospitals. Given the comorbid and elderly cohort of patients hospitalized, hospital-acquired COVID-19 infection is often fatal. Pathogen genome sequencing is becoming increasingly important in infection prevention and control (IPC). AIM: To inform the understanding of in-hospital SARS-CoV-2 transmission in order to improve IPC practices and to inform the future development of virological testing for IPC. METHODS: Patients detected COVID-19 positive by polymerase chain reaction on Ward A in April and May 2020 were included with contact tracing to identify other potential cases. Genome sequencing was undertaken for a subgroup of cases. Epidemiological, genomic, and cluster analyses were performed to describe the epidemiology and to identify factors contributing to the outbreak. FINDINGS: Fourteen cases were identified on Ward A. Contact tracing identified 16 further patient cases; in addition, eight healthcare workers (HCWs) were identified as being COVID-19 positive through a round of asymptomatic testing. Genome sequencing of 16 of these cases identified viral genomes differing by two single nucleotide polymorphisms or fewer, with further cluster analysis identifying two groups of infection (a five-person group and a six-person group). CONCLUSION: Despite the temporal relationship of cases, genome sequencing identified that not all cases shared transmission events. However, 11 samples were found to be closely related and these likely represented in-hospital transmission. This included three HCWs, thereby confirming transmission between patients and HCWs.

The impact of progesterone receptor negativity on oncological outcomes in oestrogen-receptor-positive breast cancer.

BACKGROUND: Oestrogen receptor (ER) status provides invaluable prognostic and therapeutic information in breast cancer (BC). When clinical decision making is driven by ER status, the value of progesterone receptor (PgR) status is less certain. The aim of this study was to describe clinicopathological features of ER-positive (ER+)/PgR-negative (PgR-) BC and to determine the effect of PgR negativity in ER+ disease. METHODS: Consecutive female patients with ER+ BC from a single institution were included. Factors associated with PgR- disease were assessed using binary logistic regression. Oncological outcome was assessed using Kaplan-Meier and Cox regression analysis. RESULTS: In total, 2660 patients were included with a mean(s.d.) age of 59.6(13.3) years (range 21-99 years). Median follow-up was 97.2 months (range 3.0-181.2). Some 2208 cases were PgR+ (83.0 per cent) and 452 were PgR- (17.0 per cent). Being postmenopausal (odds ratio (OR) 1.66, 95 per cent c.i. 1.25 to 2.20, P < 0.001), presenting with symptoms (OR 1.71, 95 per cent c.i. 1.30 to 2.25, P < 0.001), ductal subtype (OR 1.51, 95 per cent c.i. 1.17 to 1.97, P = 0.002) and grade 3 tumours (OR 2.20, 95 per cent c.i. 1.68 to 2.87, P < 0.001) were all associated with PgR negativity. In those receiving neoadjuvant chemotherapy (308 patients), pathological complete response rates were 10.1 per cent (25 of 247 patients) in patients with PgR+ disease versus 18.0 per cent in PgR- disease (11 of 61) (P = 0.050). PgR negativity independently predicted worse disease-free (hazard ratio (HR) 1.632, 95 per cent c.i. 1.209 to 2.204, P = 0.001) and overall survival (HR 1.774, 95 per cent c.i. 1.324 to 2.375, P < 0.001), as well as worse overall survival in ER+/HER2- disease (P = 0.004). CONCLUSIONS: In ER+ disease, PgR- tumours have more aggressive clinicopathological features and worse oncological outcomes. Neoadjuvant and adjuvant therapeutic strategies should be tailored according to PgR status.

Disease recurrence and oncological outcome of patients treated surgically with curative intent for estrogen receptor positive, lymph node negative breast cancer.

BACKGROUND: The molecular era has identified four breast cancer subtypes. Luminal A breast cancer (LABC) is defined by estrogen-receptor positive (ER+), progesterone-receptor positive (PgR+) and human epidermal growth factor receptor-2 negative (HER2-) tumours; these cancers are the most common and carry favourable prognoses. AIMS: To describe clinicopathologic features, oncological outcome and relapse patterns in LABC. METHODS: Consecutive female patients diagnosed with ER/PgR+/HER2-, lymph node negative (LN-) breast cancer between 2005 and 2015 were included. Clinicopathological and recurrence data was recorded using descriptive statistics. Oncological outcome was determined using Kaplan-Meier and Cox-regression analyses. RESULTS: Analysis was performed for 849 patients with median follow-up of 102.1 months. Mean disease-free (DFS) and overall survival (OS) were 85.8% and 91.8%. Seventy patients died during this study (8.2%), while 58 patients had recurrence; 7 had local recurrence (0.8%) and 51 had distant recurrence (DDR) (6.0%). Patients developing DDR were likely to be postmenopausal (P = 0.028), present symptomatically (P < 0.001) and have larger tumours (P < 0.001). The mean time to DDR was 65.7 months, with fatal recurrence occurring in 66.6% of patients with DDR (34/51). Systemic chemotherapy prescription did not influence DDR (P = 0.053). Age >65 (hazards ratio (HR):1.66, 95% Confidence Interval (CI):1.07-2.55, P = 0.022), presenting symptomatically (HR:2.28, 95%CI:1.21-4.29, P = 0.011) and tumour size >20 mm (HR:1.81, 95%CI:1.25-2.62, P = 0.002) predicted DFS, while age>65 (HR:2.60, 95%CI:1.49-4.53, P = 0.001) and being postmenopausal at diagnosis (HR:3.13, 95%CI:1.19-8.22, P = 0.020) predicted OS. CONCLUSION: Our series demonstrated excellent survival outcomes for patients diagnosed with LN- LABC after almost a decade of follow-up. However, following DDR, fatal progression is often imminent.

Changes in Multidisciplinary Tracheostomy Team Practice Over Time.

Aim Increasing numbers of tracheostomy patients are discharged from the Intensive Care Unit (ICU) to general hospital wards. There is evidence that a Multidisciplinary Tracheostomy Team (MTT) can have a positive impact on the care of tracheostomy patients discharged from the ICU. We compared tracheostomy management and patient outcome in two time periods, at the start of our MTT practice in 2009-2011 and again in 2017. Methods In a retrospective audit, we compared tracheostomy management and patient outcome in 117 patients who had a tracheostomy in 2009-2011 with 81 patients who had a tracheostomy in 2017. Results The duration of tracheostomy cannulation was significantly shorter (21 vs 31 days, p=0.0005) in 2017 compared to 2009-2011. A Mini-Trach was used after tracheostomy decannulation in 56 of the 81 (69%) tracheostomy patients in 2017. Conclusions The continued development of our MTT service over 8 years was associated with a significantly shorter duration of tracheostomy cannulation and the introduction of Mini-Trach use after tracheostomy decannulation. These results support the importance of maintaining an active MTT service to manage tracheostomy patients after discharge from the ICU.

A case of streptococcal surgical site infection following Mohs surgery.

Group A ß-hemolytic Streptococcal (GAS) cellulitis is an uncommon surgical site infection that presents with rapid onset of pain and swelling in the first few days after a procedure. Unlike staphylococcal cellulitis, GAS cellulitis lacks purulence and spreading erythema. The absence of these classic signs may delay the diagnosis of GAS cellulitis and lead to severe complications. We present the case of an immunosuppressed 49-year-old patient who developed swelling and severe pain at his incision site two days after undergoing Mohs micrographic surgery on his forehead. He was clinically diagnosed with GAS cellulitis and recovered with intravenous antibiotics. Unfortunately, there is a paucity of information about GAS cellulitis in the dermatologic literature and clinicians need to recognize and aggressively treat this rare but serious complication of Mohs micrographic surgery.

Deepithelialized flaps and grafts: applications in dermatologic surgery.

Deepithelialized flaps and grafts have been widely used by reconstructive surgeons in a diverse array of surgical specialties and have more recently made an appearance in dermatologic surgery. These techniques may be advantageous in their enabling of contour preservation of deep defects, reconstructions in areas of high mechanical tension, single-stage repairs, auricle reconstruction requiring tissue transfer, and reconstruction requiring free margins in areas with a paucity of local soft tissue. This article provides a review of the literature on deepithelialized flaps and grafts. We also highlight the use of these techniques in the field of dermatology and encourage appropriate application of deepithelialized flaps and grafts in dermatologic surgery.

Correction to: Breast cancer subtype discordance: impact on post-recurrence survival and potential treatment options.

It has been highlighted that the original manuscript [1] contains a typesetting error regarding the authorship.

Breast cancer subtype discordance: impact on post-recurrence survival and potential treatment options.

BACKGROUND: Recent studies have shown that breast cancer subtype can change from the primary tumour to the recurrence. Discordance between primary and recurrent breast cancer has implications for further treatment and ultimately prognosis. The aim of the study was to determine the rate of change between primary and recurrence of breast cancer and to assess the impact of these changes on survival and potential treatment options. METHODS: Patient demographics were collected on those who underwent surgery for breast cancer between 2001 and 2014 and had a recurrence with biopsy results and pathology scoring of both the primary and recurrence. RESULTS: One hundred thirty two consecutive patients were included. There were 31 (23.5%) changes in subtype. Discordance occurred most frequently in luminal A breast cancer (n = 20), followed by triple negative (n = 4), luminal B (n = 3) and HER2 (n = 3). Patients who changed from luminal A to triple negative (n = 18) had a significantly worse post-recurrence survival (p < 0.05) with overall survival approaching significance (p = 0.064) compared to concordant luminal A cases (n = 46). Overall receptor discordance rates were: estrogen receptor 20.4% (n = 27), progesterone receptor 37.7% (n = 50) and HER2 3% (n = 4). Loss of estrogen receptor and progesterone receptor was more common than gain (21 vs. 6 (p = 0.04) and 44 vs. 6 (p = 0.01) respectively). Nine patients (6.8%) gained receptor status potentially impacting treatment options. CONCLUSION: Discordance in subtype and receptor status occurs between primary and recurrent breast cancer, ultimately affecting survival and potentially impacting treatment options.

A Systematic Review of Lower Lip Anatomy, Mechanics of Local Flaps, and Special Considerations for Lower Lip Reconstruction.

Reconstruction of defects of the lower lip can be very challenging. The aim of this review is to analyze the unique characteristics of lower lip anatomy and provide a systematic approach for lower lip reconstruction. A review of current literature was performed using the PubMed database. Articles analyzing the anatomic and histologic characteristics of the lower lip, mechanics of local faps, and different lower lip reconistruction techniques were included. Articles focused on lower lip reconstruction with free faps were excluded. The orbicularis oris has been described as the main supportive mechanism, however, a number of other structures have been shown to provide mechanical support to the lower lip, including septations of connective tissue extending from the epithelium to the orbicularis oris, a fbroelastic meshwork located in the mentolabial sulcus, and subdermal muscular fibers with dermal terminations in the area of the modiolus. Depending on the location, size, and depth of the wound, a number of reconstruction options are available. Preservation of the competency of orbicularis oris, relation-ship of the modiolus with associated muscles, and sensation, are critical components of functional reconstruction. Primary closure and local faps are assessed for these 3 components and analysis is provided. In conclusion, knowledge of the static and dynamic structural support of the lower lip, as well as the characteristics of different reconstructive options, is imperative for optimal functional and aesthetic outcomes.