A meta-analysis: incidental intraductal papillary mucinous neoplasm and extra-pancreatic malignancy.

INTRODUCTION: Meta-analysis aimed to quantify the relationship between intraductal papillary mucinous neoplasm (IPMN) and increased incidence of extra-pancreatic malignancy (EPM) previously reported in qualitative observational cohort studies. METHODS: Study protocol was registered with PROSPERO (CRD42020169614) and conducted to the Meta-analysis Of Observational Studies in Epidemiology and systematic review reported with Preferred Reporting Items for Systematic Reviews and Meta-Analyses, Assessing the Methodological Quality of Systematic Reviews guidelines. RESULTS: Sixteen studies (total of 8240 patients) were included in the pooled, and 7399 patients in the subgroup meta-analyses. The odds ratio (OR) for any EPM in the presence of IPMN was 57.9 (95% confidence interval 40.5-82.7), fixed effects, I2 = 59% (p < 0.0014). Subgroup analysis for any gastrointestinal EPM (i.e. oesophagus, stomach, colon and rectum) in the presence of an IPMN estimated an overall OR of 12.9 (95% confidence interval 8.8-19.0), fixed effects, I2 = 64% (p < 0.0004). CONCLUSION: Patients with an IPMN are categorically at increased risk for a higher incidence of EPM and particularly the odds of a gastrointestinal malignancy are also increased in comparison with the general population. We advocate that patients presenting with an IPMN should be considered for gastrointestinal screening including colonoscopy, upper gastrointestinal endoscopy or computed tomography.

Clinical features associated with the development of hydrocephalus following TBI in the paediatric age group.

INTRODUCTION: Predictive factors for post-traumatic hydrocephalus (PTH) in adults have been elucidated but remain uncertain for children. We aimed to identify the prevalence of PTH in paediatric patients and identify clinical/radiological factors which may increase the probability of children developing PTH. METHODS: This was a retrospective study of all patients < 16 years old admitted to our unit with traumatic brain injury (TBI) between March 2013 and June 2018, 108 patients in total. Patients were classified as mild (13-15), moderate (9-12) or severe (3-8) TBI based on admission GCS. Three independent reviewers collected data from case notes. CT scans were reviewed for hydrocephalus using Evan's index. Two-tailed Fisher's exact tests with a p value < 0.05 were considered statistically significant. RESULTS: Median patient age was 7 years, and 65% were males (n = 70). PTH wasn't identified in any patients with mild/moderate TBI (n = 79). In cases of severe TBI (n = 29), three patients developed PTH requiring ventriculoperitoneal shunting (10%; p = 0.02). Radiological features which were significantly more common in the PTH group were intraventricular haemorrhage (p = 0.05) and subarachnoid haemorrhage (p = 0.03). There was also a trend towards a statistically significant association with subdural haematoma (p = 0.07). The need for other neurosurgical procedures, such as fracture elevation and craniotomy, did not increase the probability of developing with PTH (p = 0.08). DISCUSSION: The prevalence of PTH in our study is 2.7%. Factors which may be associated with a higher probability of developing PTH may include IVH, SAH, severity of TBI, and subdural haematoma. We propose a national prospective multicentre database of paediatric PTH. The data collected on prevalence, presentation, risk factors, and management could guide contemporary management and improve the outcomes of children with PTH.

Crop manuring and intensive land management by Europe's first farmers.

The spread of farming from western Asia to Europe had profound long-term social and ecological impacts, but identification of the specific nature of Neolithic land management practices and the dietary contribution of early crops has been problematic. Here, we present previously undescribed stable isotope determinations of charred cereals and pulses from 13 Neolithic sites across Europe (dating ca. 5900-2400 cal B.C.), which show that early farmers used livestock manure and water management to enhance crop yields. Intensive manuring inextricably linked plant cultivation and animal herding and contributed to the remarkable resilience of these combined practices across diverse climatic zones. Critically, our findings suggest that commonly applied paleodietary interpretations of human and herbivore δ(15)N values have systematically underestimated the contribution of crop-derived protein to early farmer diets.

Practical considerations in the determination of compound-specific amino acid δ15N values in animal and plant tissues by gas chromatography-combustion-isotope ratio mass spectrometry, following derivatisation to their N-acetylisopropyl esters.

RATIONALE: Stable nitrogen isotope (δ(15)N) values of bone collagen are routinely used to inform interpretations of diet and trophic positions within contemporary and ancient ecosystems, yet the underlying physiological and biochemical factors which contribute to the bulk collagen δ(15)N value remain little understood. Determination of individual amino acid (AA) δ(15)N values in animal and plant proteins can help to elucidate the cycling of nitrogen and inform predictions of palaeodiet and ecology. METHODS: In this study we present a methodology for the measurement of amino acid δ(15)N values using gas chromatography-combustion-isotope ratio mass spectrometry (GC-C-IRMS). Amino acid standards of known δ(15)N values were derivatised to their N-acetylisopropyl (NAIP) esters and purified through Dowex ion-exchange resin to determine any isotopic fractionation associated with derivatisation and ion-exchange chromatography. The effect of starch on AA δ(15)N values was also determined by hydrolysing bone collagen with and without the presence of starch. RESULTS: The amino acids derivatised to their NAIP esters give values within ±0.8‰ of their δ(15)N values measured separately by elemental analyser (EA)-IRMS, with a precision of better than 0.8‰. The δ(15)N values of AAs after Dowex ion-exchange chromatography were within ±0.9‰ of their values prior to ion-exchange chromatography. The AA δ(15)N values of bone collagen hydrolysed with and without starch were within ±0.8‰. CONCLUSIONS: Hydrolysis of lipid-extracted plant material followed by purification of AAs using Dowex ion-exchange resin and derivatisation to their NAIP esters is a suitable protocol for the accurate determination of individual plant and animal AA δ(15)N values by GC-C-IRMS.

The AAMC Standardized Video Interview: Lessons Learned From the Residency Selection Process.

Calls to change the residency selection process have increased in recent years, with many focusing on the need for holistic review and alternatives to academic metrics. One aspect of applicant performance to consider in holistic review is proficiency in behavioral competencies. The Association of American Medical Colleges (AAMC) developed the AAMC Standardized Video Interview (SVI), an online, asynchronous video interview that assesses applicants' knowledge of professionalism and their interpersonal and communication skills. The AAMC worked with the emergency medicine community to pilot the SVI. Data from 4 years of research (Electronic Residency Application Service [ERAS] 2017-2020 cycles) show the SVI is a reliable, valid assessment of these behavioral competencies. It provides information not available in the ERAS application packet, and it does not disadvantage individuals or groups. Yet despite the SVI's psychometric properties, the AAMC elected not to renew or expand the pilot in residency selection.In this Invited Commentary, the authors share lessons learned from the AAMC SVI project about introducing a new tool for use in residency selection. They recommend that future projects endeavoring to find ways to support holistic review engage all stakeholders from the start; communicate the value of the new tool early and often; make direct comparisons with existing tools; give new tools time and space to succeed; strike a balance between early adopters and broad participation; help stakeholders understand the limitations of what a tool can do; and set clear expectations about both stakeholder input and pricing. They encourage the medical education community to learn from the SVI project and to consider future partnerships with the AAMC or other specialty organizations to develop new tools and approaches that prioritize the community's needs. Finding solutions to the challenges facing residency selection should be a priority for all stakeholders.

Of cattle and feasts: Multi-isotope investigation of animal husbandry and communal feasting at Neolithic Makriyalos, northern Greece.

The aim of this study is to investigate livestock husbandry and its relationship to the mobilization of domestic animals for slaughter at large communal feasting events, in Late Neolithic Makriyalos, northern Greece. A multi-isotope approach is built that integrates analysis of: δ13C and δ15N values of human and animal bone collagen for understanding long-term dietary behavior,Incremental δ13C and δ18O values of domestic animal tooth enamel carbonate for assessing seasonal patterns in grazing habits and mobility, and87Sr/86Sr ratios of cattle tooth enamel for examining the possibility that some of the animals consumed at the site were born outside the local environment. The findings indicate that cattle had isotopically more variable diets than sheep, which may reflect grazing over a wider catchment area in the local landscape. Cattle products did not make a significant contribution to the long-term dietary protein intake of the humans, which may indicate that they were primarily consumed during episodic feasting events. There is no indication that pasturing of livestock was pre-determined by their eventual context of slaughter (i.e. large-scale feasting vs. more routine consumption events). Two non-local cattle identified among those deposited in a feasting context may have been brought to the site as contributions to these feasts. The evidence presented provides a more detailed insight into local land use and into the role of livestock and feasting in forging social relationships within the regional human population.

Combining functional weed ecology and crop stable isotope ratios to identify cultivation intensity: a comparison of cereal production regimes in Haute Provence, France and Asturias, Spain.

This investigation combines two independent methods of identifying crop growing conditions and husbandry practices-functional weed ecology and crop stable carbon and nitrogen isotope analysis-in order to assess their potential for inferring the intensity of past cereal production systems using archaeobotanical assemblages. Present-day organic cereal farming in Haute Provence, France features crop varieties adapted to low-nutrient soils managed through crop rotation, with little to no manuring. Weed quadrat survey of 60 crop field transects in this region revealed that floristic variation primarily reflects geographical differences. Functional ecological weed data clearly distinguish the Provence fields from those surveyed in a previous study of intensively managed spelt wheat in Asturias, north-western Spain: as expected, weed ecological data reflect higher soil fertility and disturbance in Asturias. Similarly, crop stable nitrogen isotope values distinguish between intensive manuring in Asturias and long-term cultivation with minimal manuring in Haute Provence. The new model of cereal cultivation intensity based on weed ecology and crop isotope values in Haute Provence and Asturias was tested through application to two other present-day regimes, successfully identifying a high-intensity regime in the Sighisoara region, Romania, and low-intensity production in Kastamonu, Turkey. Application of this new model to Neolithic archaeobotanical assemblages in central Europe suggests that early farming tended to be intensive, and likely incorporated manuring, but also exhibited considerable variation, providing a finer grained understanding of cultivation intensity than previously available.

Stable Carbon Isotope Evidence for Neolithic and Bronze Age Crop Water Management in the Eastern Mediterranean and Southwest Asia.

In a large study on early crop water management, stable carbon isotope discrimination was determined for 275 charred grain samples from nine archaeological sites, dating primarily to the Neolithic and Bronze Age, from the Eastern Mediterranean and Western Asia. This has revealed that wheat (Triticum spp.) was regularly grown in wetter conditions than barley (Hordeum sp.), indicating systematic preferential treatment of wheat that may reflect a cultural preference for wheat over barley. Isotopic analysis of pulse crops (Lens culinaris, Pisum sativum and Vicia ervilia) indicates cultivation in highly varied water conditions at some sites, possibly as a result of opportunistic watering practices. The results have also provided evidence for local land-use and changing agricultural practices.

Cereal grain, rachis and pulse seed amino acid δ15N values as indicators of plant nitrogen metabolism.

Natural abundance δ(15)N values of plant tissue amino acids (AAs) reflect the cycling of N into and within plants, providing an opportunity to better understand environmental and anthropogenic effects on plant metabolism. In this study, the AA δ(15)N values of barley (Hordeum vulgare) and bread wheat (Triticum aestivum) grains and rachis and broad bean (Vicia faba) and pea (Pisum sativum) seeds, grown at the experimental farm stations of Rothamsted, UK and Bad Lauchstädt, Germany, were determined by GC-C-IRMS. It was found that the δ(15)N values of cereal grain and rachis AAs could be largely attributed to metabolic pathways involved in their biosynthesis and catabolism. The relative (15)N-enrichment of phenylalanine can be attributed to its involvement in the phenylpropanoid pathway and glutamate has a δ(15)N value which is an average of the other AAs due to its central role in AA-N cycling. The relative AA δ(15)N values of broad bean and pea seeds were very different from one another, providing evidence for differences in the metabolic routing of AAs to the developing seeds in these leguminous plants. This study has shown that AA δ(15)N values relate to known AA biosynthetic pathways in plants and thus have the potential to aid understanding of how various external factors, such as source of assimilated N, influence metabolic cycling of N within plants.

The effect of manuring on cereal and pulse amino acid δ(15)N values.

Amino acid δ(15)N values of barley (Hordeum vulgare) and bread wheat (Triticum aestivum) grains and rachis and broad bean (Vicia faba) and pea (Pisum sativum) seeds, grown in manured and unmanured soil at the experimental farm stations of Rothamsted, UK and Bad Lauchstädt, Germany, were determined by GC-C-IRMS. Manuring was found to result in a consistent (15)N-enrichment of cereal grain amino acid δ(15)N values, indicating that manuring did not affect the metabolic routing of nitrogen (N) into cereal grain amino acids. The increase in cereal grain δ(15)N values with manuring is therefore due to a (15)N-enrichment in the δ(15)N value of assimilated inorganic-N. Greater variation was observed in the (15)N-enrichment of rachis amino acids with manuring, possibly due to enhanced sensitivity to changes in growing conditions and higher turnover of N in rachis cells compared to cereal grains. Total amino acid δ(15)N values of manured and unmanured broad beans and peas were very similar, indicating that the legumes assimilated N2 from the atmosphere rather than N from the soil, since there was no evidence for routing of (15)N-enriched manure N into any of the pulse amino acids. Crop amino acid δ(15)N values thus provide insights into the sources of N assimilated by non N2-fixing and N2-fixing crops grown on manured and unmanured soils, and reveal an effect of manure on N metabolism in different crop species and plant parts.

Transition-metal-free catalytic synthesis of 1,5-diaryl-1,2,3-triazoles.

1,5-Diarylsubstituted 1,2,3-triazoles are formed in high yield from aryl azides and terminal alkynes in DMSO in the presence of catalytic tetraalkylammonium hydroxide. The reaction is experimentally simple, does not require a transition-metal catalyst, and is not sensitive to atmospheric oxygen and moisture.