Indirect Evidence Research Articles

Lebrikizumab (Ebglyss)

Canada’s Drug Agency (CDA-AMC) recommends that Ebglyss should not be reimbursed by public drug plans for the treatment of moderate to severe atopic dermatitis (AD) in adults and adolescents aged 12 years and older with a body weight of at least 40 kg, whose disease is not adequately controlled with topical prescription therapies or when those therapies are not advisable. Evidence from 3 clinical trials demonstrated that, in the short-term, Ebglyss treatment improved the severity of AD and reduced itch symptoms compared with placebo in adults and adolescents with moderate to severe AD. However, based on the evidence reviewed in the initial meeting and the reconsideration meeting, the Canadian Drug Expert Committee (CDEC) could not determine whether lebrikizumab would address the unmet needs of patients because of the uncertainty around the benefit of lebrikizumab versus appropriate comparators and in patients who received prior dupilumab or Janus kinase (JAK) inhibitor treatment. No evidence was submitted that directly compared Ebglyss to currently available treatments for AD. The indirect evidence submitted had limitations that impacted the certainty of the evidence, and it was unclear if the estimates were valid. The safety of Ebglyss relative to other treatments for AD is unknown because no comparative evidence was submitted. In addition, longer-term safety and efficacy was uncertain because of limitations of the study designs and analysis with the available evidence.

Effects of different types of intermittent fasting on metabolic outcomes: an umbrella review and network meta-analysis.

Intermittent fasting (IF) holds promise for enhancing metabolic health. However, the optimum IF forms and their superiority over continuous energy restriction (CER) remain unclear due to disconnected findings. We systematically searched PubMed, Embase, and the Cochrane databases for meta-analyses of randomized controlled trials (RCTs) investigating the association between IF and metabolic health outcomes. Subsequently, we performed an umbrella review and network meta-analysis (NMA) to evaluate the efficacy of different forms of IF (time-restricted eating (TRE), alternate-day fasting (ADF), and 5:2 diet (regular eating for 5days and energy restriction for 2days per week)) compared to CER and usual diets on metabolic health outcomes. To assess the certainty of both direct and indirect estimates, we employed the Confidence in Network Meta-Analysis (CINeMA) approach. Additionally, we calculated the surface under the cumulative ranking curve (SUCRA) for each dietary strategy to determine their ranking in terms of metabolic health benefits. Ten of the best and non-redundant meta-analysis studies, involving 153 original studies and 9846 participants, were included. When considering direct evidence only, all IF forms significantly reduced body weight compared to usual diets. In NMAincorporating indirect evidence, all IF regimens alsosignificantly reduced body weight compared to usual diets. In the SUCRA of NMA, IF ranked higher than usual diets or CER in 85.4% and 56.1% of the outcomes, respectively. ADF had the highest overall ranking for improving metabolic health (ranked first: 64.3%, ranked second: 14.3%). Overall, all IF forms demonstrate potentials to improve metabolic health, with ADF appearing to produce better outcomes across investigated outcomes. Further high-quality trials are warranted to confirm the (relative) efficacy of IF on metabolic health. PROSPERO (record no: CRD42022302690).

Differences in xylem and phloem structure in living stumps of Norway spruce (Picea abies (L.) Karst.) and silver fir (Abies alba Mill.)

Summary Living stumps reported in many tree species were the first, circumstantial evidence of root grafting. Although stump overgrowth has been extensively studied in various tree species, anatomical observations have mainly focused on the xylem part. Here, we investigated the xylem and phloem structure in living stumps of two conifer species: Norway spruce (Picea abies (L.) Karst.) and silver fir (Abies alba Mill.). The mechanism of wound closure was similar in the two species, however, there were differences in the structure of wound tissues in wood and bark. Immediately after the injury, a callus consisting of parenchymal cells was formed, followed by wound-wood with wide increments. In addition, the wood structure and morphology of tracheids were changed. Tracheids lost their typical elongated and tapering structure; instead, numerous crooked and forked tracheids were present. Traumatic resin canals were present in both species but were more abundant in P. abies, which also had normal resin canals. While the structure of the xylem growth rings eventually normalized in both species, the width of the annual xylem increments was diminished. In both species, the typical structure of annual phloem increment was lost in the non-collapsed phloem and sclereids were very abundant in the collapsed phloem. In A. alba, the collapsed phloem was rich in swollen parenchyma cells containing blue-stained contents, while in P. abies, numerous large traumatic resin canals were conspicuous. The study showed that similar patterns of vascular tissue restoration exist in A. alba and P. abies in response to tree felling. However, there are certain species-specific peculiarities in the wood and phloem anatomical response, which might affect long-term stump functioning and survival.

Captive swedes and the formation of mathematical cartography in Siberia (1711–1722)

After the defeat of Charles XII at Poltava, thousands of soldiers and officers of his army ended up in Russian captivity. Many of them were then exiled beyond the Urals, where they lived from 1711 to 1722. It is the Swedish officers that the beginnings of mathematical cartography of Siberia are associated with. The article analyzes the aspects of the work of the best known Swedish cartographer, Captain Philip Johan Tabbert (Philipp Johann von Strahlenberg) and provides information about other Swedes who engaged in cartography. At the early stage of the formation of mathematical cartography, an important problem was converting Russian linear measures into degrees. Various ratios used by both the Swedish captives and the Russian land surveyors are given. The methodology for longitude coordinates determination was studied based on the analysis of the maps and diary entries, made by Tabbert during D. G. Messerschmidt’s expedition. Indirect evidence of measurements of latitudinal coordinates, carried out by Swedish captives before the arrival of Russian surveyors in Siberia, has been collected. All of this enabled the analysis of mathematical basis of the two manuscript maps made by the Swedes in Siberia. It is concluded that the geographical maps, drawn in the Siberian captivity by Charles XII’s officers, continued the European tradition of mapping Siberia, being a separate stage in this process. What distinguished such maps was that their authors lived in the region they mapped. The Swedish captives became the first cartographers of Siberia, who created mathematically precise geographical maps with a grade grid, rather than hand-drawn, artistic maps. At the same time, Swedish officers’ efforts associated with creating geographical maps of Siberia had no impact on the development of Russian cartography. It was not the Swedes who broke the tradition of cartographic isography but, rather, the Russian graduates of the Maritime Academy who began working in Siberia in 1719.

Exploring the relationship between cardiac awareness and balance

SummaryPostural balance requires the interplay between several physiological signals. Indirect evidence suggests that the perception of signals arising from the autonomic nervous system might play a role (e.g. cardiac awareness). Here, we tested this hypothesis by investigating the relationship between postural control and cardiac awareness (i.e. interoception) in a sample of N = 70 healthy individuals. Postural control was measured using a medical robotic device, while cardiac awareness was evaluated using the heartbeat counting task. A within-subject design included two platform configurations (static, unstable) and two visual feedback conditions (eyes open, eyes closed). For each condition, we measured the sway area and the range of oscillation of the platform, as well as the range of oscillation and the quantity of movement of participants’ trunk. In the “platform unstable, eyes closed” condition, participants with higher cardiac awareness demonstrated a significantly smaller sway area and reduced oscillations of both the platform and their trunk. These findings hint at a potential link between interoception and postural control, suggesting that the perception of internal body signals might sustain balance.

Evolution of WHO COVID-19 mask guidelines amid intense demands for rapid advice.

During a health emergency, there is an urgent need to rapidly develop guidelines that meet minimum quality standards, as exemplified by the development of WHO guidelines on mask use in health care and community settings during the COVID-19 pandemic. Between January 2020 and October 2023, WHO developed 21 guideline updates on the use of masks as part of infection prevention and control (IPC) practices. Guideline developers had to deal with an ever-growing volume of evidence of variable quality. Initially, indirect evidence drawn from other severe respiratory illnesses and established minimum requirements for IPC were used. As direct evidence began to emerge, WHO commissioned a living systematic review on mask use in June 2020, which formed the basis of evidence-to-decision making. As more evidence became available, additional considerations were incorporated into the process of recommendation formulation, including harms, acceptability, feasibility and resource use. Target populations for the mask guidelines expanded to include the general public, including children. A broad range of disciplines supported guideline development, including IPC, epidemiology, infectious diseases, occupational health, engineering, pneumology, paediatrics, and water, sanitation and hygiene, as well as civil society representatives. Additional expertise was engaged in the areas of ventilation and aerobiology to expand the range of perspectives regarding modes of transmission. Despite challenges, the experience of rapidly and regularly updating advice on mask use during an emergency health response has shown that it is possible to apply the minimum standards for ensuring the guideline methodology is trustworthy and transparent, with increasing rigor over time as evidence improves. Overall, the experience of developing guidelines during the COVID-19 pandemic underscores the importance of adapting to evolving evidence, incorporating diverse perspectives, and maintaining transparency to ensure a rigorous methodology and in return guideline trustworthiness and effectiveness.

Protein requirement in obesity.

The combined obesity and ageing pandemic require action to avoid a total health system infarct. Obesity is largely challenged with caloric restriction and endurance exercise, likely to be assisted by drugs. The older adults with the highest obesity levels may face extreme loss of muscle mass and increased risk of sarcopenic obesity.Within this context the question of what is the protein requirement is extremely urgent. While the topic is essential, no trials have directly assessed protein requirements for obesity. Therefore, we will have to deal with more indirect evidence. Several systematic reviews have appeared for obesity treatment involving protein and a few randomized controlled trials during weight loss are worth mentioning considering the amount of protein needed, especially with increasing age. Protein requirements are hard to derive for obesity defined by BMI over 30 perse. During weight loss the rebuilding of the body is likely to need at least 1.2 g/kg body weight/d with a maximum weight of BMI 30, especially in the aged. Obesity might increase protein requirements, however being obese with a healthy and active lifestyle might result in normal protein requirements.

Reconstruction of the Total Solar Irradiance During the Last Millennium

Solar irradiance variations across various timescales, from minutes to centuries, represent a potential natural driver of past regional and global climate cold phases. To accurately assess the Sun’s effect on climate, particularly during periods of exceptionally low solar activity, known as grand minima, an accurate reconstruction of solar forcing is essential. While direct measurements of the total solar irradiance (TSI) only began in the late 1970s, with the advent of space radiometers, indirect evidence from various historical proxies suggests that the Sun’s magnetic activity has undergone possible significant fluctuations over much longer timescales. Employing diverse and independent methods for TSI reconstruction is essential to gaining a comprehensive understanding of this issue. This study employs a semi-empirical model to reconstruct TSI over the past millennium. Our approach uses an estimated open solar magnetic field (F o ), derived from cosmogenic isotope data, as a proxy for solar activity. We reconstruct the cyclic variations of TSI, due to the solar surface magnetic features, by correlating F o with the parameter of active region functional form. We obtain the long-term TSI trend by applying the empirical mode decomposition algorithm to the reconstructed F o to filter out the 11 yr and 22 yr solar variability. We prepare a reconstructed TSI record, spanning 971 to 2020 CE. The estimated departure from modern TSI values occurred during the Spörer minimum (around 1400 CE), with a decrease of approximately 2.3 Wm−2. A slightly smaller decline of 2.2 Wm−2 is reported during the Maunder minimum, between 1645 and 1715 CE.

Pharmacologic prophylaxis of postoperative delirium in elderly patients: A network meta-analysis of randomized controlled trials

BackgroundThe high incidence and mortality rates of postoperative delirium (POD) among elderly patients highlights the pressing need for tailored prophylactic strategies. Despite various pharmacologic prophylactic strategies have been reported effective, their overall benefit and safety remain unclear in the geriatric population. Our network meta-analysis (NMA) aimed to systematically evaluate and rank the effectiveness of various pharmacological interventions in preventing POD in elderly patients. MethodsWe conducted an extensive search of PubMed, Embase, Cochrane Central Register of Controlled Trials, PsycINFO, and Google Scholar for randomized controlled trials (RCTs) published up to August 1, 2023. We included RCTs examining pharmacological prophylactic effects of POD in elderly patients. To extract data in alignment with predefined areas of interest, we employed the Preferred Reporting Items for Systematic Reviews and Meta-analyses guidelines. The primary outcome was the incidence of POD. For secondary outcomes, we evaluated tolerability through all-cause discontinuation or drop-out rates, as well as all-cause mortality. ResultsOur analysis encompassed a total of 44 RCTs involving 11,178 patients. Out of these, 26 RCTs involved comparisons with placebo only. For delirium prevention, the treatment groups receiving atypical antipsychotics (odds ratio (OR) of 0.27 and 95% confidence interval (CI) of 0.12-0.58), haloperidol (OR of 0.42; 95% CI of 0.25-0.71), dexmedetomidine (OR of 0.51 and 95% CI of 0.37-0.71 and melatonergic agents (MMA) (OR of 0.57 and 95% CI of 0.33-0.98) had significantly lower rates of delirium compared to the placebo group. Notably, the atypical antipsychotics ranked as the most effective treatment. For tolerability, no statistically differences in rates of dropout discontinuation and all-cause mortality among groups allocated to the placebo or individual pharmacological treatments. ConclusionsBased on indirect evidence, our network meta-analysis identified atypical antipsychotics, dexmedetomidine, MMA, and haloperidol as effective in preventing POD in the elderly, with atypical antipsychotics ranking highest. However, it is essential to note that these findings should be confirmed through further RCTs.

Lost and found: a 100-year-old educational neurosurgical film by Thierry de Martel, pioneer of French neurosurgery.

Exchanges in medical practice are necessary for training. The use of movies for promoting medical practice was introduced in the late 19th century. The authors analyzed an unidentified movie titled Trepanation for Rolandic Zone Tumor (Trépanation pour tumeur de la zone rolandique) stored at the Établissement de Communication et de Production Audiovisuelle de la Défense of the French Ministry of Armed Forces. This silent black-and-white movie, lasting 15 minutes and depicting the removal of a meningioma, did not contain information or a legend. The surgical tools used were those developed by Thierry de Martel. The furniture and interior design shown in the film corresponded with the Vercingétorix Clinic that this surgeon had acquired in Paris. A publication from 1922 contained 14 pictures taken from the movie presented in this paper and referred to a movie directed in 1911 by Thierry de Martel. This is strong circumstantial evidence that the film was directed and the surgery was performed by Thierry de Martel at the Vercingétorix Clinic in Paris, France, in 1911 while using the technology of the Gaumont company. This is a contemporary testimony to what surgical practice was over a century ago, and it illustrates how movies were, and remain, a unique way to learn and teach medicine.

Sequencing and Analysis of Wolbachia Strains from A and B Supergroups Detected in Sylvatic Mosquitoes from Brazil

Wolbachia are endosymbiotic bacteria that infect a wide range of arthropods and filarial nematodes, often manipulating host reproduction. The efficacy of Wolbachia-based interventions for dengue and chikungunya control has been validated through numerous field studies in recent years. This study aimed to investigate the diversity and prevalence of Wolbachia infections in sylvatic mosquitoes from two locations in Recife, Brazil. Multiple mosquito species were screened for Wolbachia using both target marker gene amplification coupled with Sanger sequencing and whole-genome sequencing (WGS) approaches. Phylogenetic analyses were conducted to classify Wolbachia strains into supergroups and assess their evolutionary relationships. Results revealed the presence of Wolbachia in eleven mosquito species examined, with different infection rates. Both supergroups A and B of Wolbachia strains were identified, with Aedes albopictus showing co-infection by both supergroups through the WGS approach. We also detected indirect evidence of Wolbachia horizontal transmission among mosquitoes and other distant host orders. This study provides valuable insights into the distribution and diversity of Wolbachia in sylvatic mosquitoes from Brazil and adds new important data about Wolbachia detection through target marker gene amplicon coupled with Sanger sequencing and WGS methods, highlighting its complementarity to ascertain the presence of Wolbachia in mosquito samples.

Stabilization of Ethane-like Dianionic Diborane(6) in Monometallic Titanium Complexes and its Subsequent B(sp3)-B(sp3) Bond Cleavage.

Treatment of [Cp*TiCl3] with [LiBH4∙THF] followed by thermolysis with [Ph2E2] (E = S or Se) resulted in the formation of classical diborane(6) complexes, [(Cp*Ti)(η4-B2H4LL')] (L = C6H4E; L' = C6H5E; 1a: E = S, 1b: E = Se), stabilized at titanium template. To the best of our knowledge, they are the first examples of mono-metallic classical diborane(6) complexes. The bonding analysis and theoretical studies suggest that the stabilization of these diborane(6) species is due to the presence of four bridging ligands in ĸ4-fashion, where two of them are phenyl thiolates/selenolates that provide more electrons to the electron-deficient titanium center. Reactions of these diborane(6) species with [M(CO)5∙THF] (M = Mo, W) led to the cleavage of electron-precise B(sp3)-B(sp3) bond that yielded ĸ3-hydridoborato complexes [(Cp*Ti)(ĸ3-BH3R)(μ-EPh)2{M(CO)4}] (2a-c: R = H, 3a-c: R = Ph). In an attempt to isolate the Te-analogue of 1a-b, a similar reaction was performed; however, the complex was too unstable to be isolated. Interestingly, the treatment of this unstable intermediate with [W(CO)5∙THF] yielded [(Cp*Ti)(ĸ3-BH3R)(μ-TePh)2{W(CO)4}] (2d: R = H, 3d: R = Ph) that are analogues of 2a-c and 3a-c, respectively. Formation of these species provide indirect evidence forexistence of unstable [(Cp*Ti)(η4-B2H4LL')] (L = C6H4Te; L' = C6H5Te; 1c).

Stabilization of Ethane‐like Dianionic Diborane(6) in Monometallic Titanium Complexes and its Subsequent B(sp3)‐B(sp3) Bond Cleavage

Treatment of [Cp*TiCl3] with [LiBH4∙THF] followed by thermolysis with [Ph2E2] (E = S or Se) resulted in the formation of classical diborane(6) complexes, [(Cp*Ti)(η4‐B2H4LL')] (L = C6H4E; L' = C6H5E; 1a: E = S, 1b: E = Se), stabilized at titanium template. To the best of our knowledge, they are the first examples of mono‐metallic classical diborane(6) complexes. The bonding analysis and theoretical studies suggest that the stabilization of these diborane(6) species is due to the presence of four bridging ligands in ĸ4‐fashion, where two of them are phenyl thiolates/selenolates that provide more electrons to the electron‐deficient titanium center. Reactions of these diborane(6) species with [M(CO)5∙THF] (M = Mo, W) led to the cleavage of electron‐precise B(sp3)‐B(sp3) bond that yielded ĸ3‐hydridoborato complexes [(Cp*Ti)(ĸ3‐BH3R)(μ‐EPh)2{M(CO)4}] (2a‐c: R = H, 3a‐c: R = Ph). In an attempt to isolate the Te‐analogue of 1a‐b, a similar reaction was performed; however, the complex was too unstable to be isolated. Interestingly, the treatment of this unstable intermediate with [W(CO)5∙THF] yielded [(Cp*Ti)(ĸ3‐BH3R)(μ‐TePh)2{W(CO)4}] (2d: R = H, 3d: R = Ph) that are analogues of 2a‐c and 3a‐c, respectively. Formation of these species provide indirect evidence for existence of unstable [(Cp*Ti)(η4‐B2H4LL')] (L = C6H4Te; L' = C6H5Te; 1c).

Combined radiographic and ultrasound evaluations to decipher joint involvement in the hands of patients with systemic sclerosis.

The objective of this study was to explore the etiologies and contributing factors of synovial and tenosynovial involvement in SSc, as well as to assess the phenotype of patients with these synovial and tenosynovial features. 171 SSc patients with hand manifestations (either vascular, skin or joint manifestations) who underwent standard X-rays of both hands and hand ultrasound (US), were included. Two independent evaluators recorded the presence or absence of acro-osteolysis, calcinosis, microcrystalline and degenerative rheumatisms, including osteophytosis on X-Rays. The presence of synovitis and tenosynovitis (active or fibrotic) was assessed through US by a third evaluator, blinded for X-ray parameters. In multivariate analysis, the characteristics associated with active synovitis and tenosynovitis were CRP>10mg/L (p = 0.013), fibrotic tenosynovitis on US (p = 0.005), anti-RNA polymerase III antibodies (p = 0.043) and poly-osteophytosis on hand X-rays (p = 0.001). After exclusion of patients with RA (n = 5) and/or poly-osteophytosis (n = 53), 14 remaining patients (12.7%) had active synovitis and/or tenosynovitis on US. In multivariate analyses, parameters associated with active synovitis and/or tenosynovitis in this selected population were scleroderma renal crisis (p = 0.012) and fibrotic tenosynovitis on US (p < 0.001). Our study confirms that osteophytosis is a significant contributor of joint involvement in SSc patients based on real life data. After exclusion of potential confounders, more than 10% of SSc patients still had active synovitis and/or tenosynovitis on US, providing indirect evidence for the existence of a specific SSc-related synovial and/or tenosynovial involvement.

Protective role of reactive aluminum phases to stabilize soil organic matter against long-term cultivation in the humid tropics under volcanic influence

ABSTRACT Cultivation can cause rapid depletion of soil organic matter (SOM), particularly in the humid tropics. Understanding the factors controlling SOM storage is a key step toward effective soil management for sustainable crop production. While clay + silt content is known to be an important factor for soil organic carbon (SOC) storage, recent studies have shown greater importance of oxalate-extracted Al (Alo; roughly corresponds to short-range-order aluminosilicate minerals and organo-Al complexes) and Fe (Feo). However, the extent to which these mineralogical factors control the response of SOM pool to land-use changes remains unclear, especially in the tropics. This study aimed to clarify the factors regulating SOM content in croplands compared to secondary forests or home gardens in Negros Occidental, Philippines. Along two line transects having a wide range of Alo contents, soil samples were collected at a depth of 0 − 10 cm from sugarcane sites (n = 33; long-term continuous cultivation of >70 years) that were paired with either secondary forests (n = 10) or home gardens (n = 20). Sugarcane sites had significantly lower SOC and total nitrogen (N) contents than secondary forest and home garden sites, whereas there was no clear difference between the latter two land uses. Both SOC and total N contents showed significant positive correlations with Alo content and, to a much less extent, with Feo content, but not with clay + silt content. The slope of the regression line between SOC and Alo was indifferent between sugarcane and the other two land uses, while the intercept was significantly lower in the sugarcane sites. These results suggest the protective role of Alo phases in both agricultural and forest soils and the presence of unprotected SOM (e.g. plant litter) in the latter sites. Furthermore, δ13C analysis suggested that the proportion of forest (C3 plant) derived carbon remaining in the sugarcane soils ranged between 10% and 50% and increased with Alo content. Together, our study showed indirect evidence of Alo-induced stabilization of SOM against long-term cultivation under the humid tropical environment.

Enhancing anti-corruption via investment arbitration: from red flags to due diligence

Abstract As the number of corruption allegations in investor–State disputes (ISDS) grows, tribunals must balance their duty to resolve disputes and to render enforceable awards. Given the difficulty of proving corruption, arbitrators increasingly consider red flags to detect it, but still struggle with drawing consequences for corrupt conduct that would serve as an effective deterrent. Our empirical analysis of 92 ISDS cases that involved allegations of corruption reveals that over a quarter of arbitral decisions already utilize a red flags approach, which helps tribunals assess corruption risks and provide circumstantial evidence. This article proposes a novel list of red flags based on the empirical analysis, domestic and international law sources as well as soft law instruments. It then frames a corresponding anti-corruption due diligence mechanism, which can minimize the risks of corruption occurring, bring more predictability to ISDS and disincentivize frivolous allegations of corruption.

Grasping time - longevity of vascularized composite allografts.

Despite significant advancements in the field of vascularized composite allotransplantation, challenges, particularly regarding the long-term viability and functionality of vascularized composite allotransplantation (VCA) grafts, persist. This paper provides a review of the current literature on the longevity of VCA grafts, focusing on factors influencing graft survival, immunological considerations and clinical outcomes. Longevity of VCA grafts is influenced by a variety of peri- and postoperative factors including cold ischemia time, human leukocyte antigen matching, environmental exposure, psychosocial factors, adherence, immunosuppression, and complications. Due to the limited number of VCA transplants performed and heterogenous reporting, direct correlation of single factors with VCA outcomes remains inconclusive. Indirect evidence, however, supports their importance. High immunosuppressive burden, frequent occurrence of acute and accumulating cases of chronic rejection remain a significant challenge of the field. Insights gained from this review aim to inform clinical practice and guide future research endeavors with the goal of ameliorating outcomes after VCA transplantation and facilitate wider use of VCA grafts for restoration of tissue defects.

Balancing act: The dynamic relationship between nutrient availability and plant defence.

Plants depend heavily on soil nutrients for growth, development and defence. Nutrient availability is crucial not only for sustaining vital biochemical processes but also for mounting effective defences against a diverse array of pathogens. Macronutrients such as nitrogen, phosphorus and potassium significantly influence plant defence mechanisms by providing essential building blocks for the synthesis of defence compounds, immune signalling and physiological responses like stomatal regulation. Micronutrients like zinc, copper and iron are essential for balancing reactive oxygen species and other reactive compounds in plant immune responses. Although substantial circumstantial evidence links nutrient availability to plant defence, the molecular mechanisms underlying this process have only recently started to be understood. This review focuses on summarizing recent advances in understanding the molecular mechanisms by which nitrogen, phosphorus and iron interact with plant defence mechanisms and explores the potential for engineering nutritional immunity in crops to enhance their resilience against pathogens.

Mammalian colonic contribution of amino acids to whole-body homeostasis.

The colon is an effective bioreactor with auxotrophic microbiota that can serve by hydrolyzing dietary and endogenous protein, as well as by synthesizing essential amino acids through nitrogen salvage. Due to assumed negligible amino acid absorption, this colonic contribution was thought to be minimal, but this may not be true. Several studies that examined the colonic environment in health and disease, show the presence of proteases in the colonic lumen, which are of both host and microbial origin, along with indirect evidence of amino acid transporters in the colonic epithelium. There are also amino acid biosynthetic pathways in the microflora, and the contribution of colonic amino acid to host amino acid nutrition has been shown in wild animals. Yet, current direct and quantitative evidence on amino acid absorption in human colon is minimal. Although amino acid absorption in colon is not very well established, current studies show that substantial amounts of amino acid could possibly be contributed to the host by the colon. There is a need for assessing this contribution quantitatively using direct isotopic methods under different nutritional conditions, dietary intakes, and clinical conditions.

How neighbourhood effects vary by achievement level

Abstract After long-standing calls for research into ‘for whom’ neighbourhood matters, the literature has recently gained traction, focussing on background characteristics such as gender, race, and socioeconomic background. However, there is still scarce and only indirect evidence on whether neighbourhood effects vary by children’s academic ability. In this paper, we combine the Neighbourhood Choice Model with quantile regressions to investigate whether neighbourhood effects vary by children’s academic proneness. Using Norwegian register data, we demonstrate heterogeneity in the effects of neighbourhood deprivation as a function of students’ proneness to academic achievement. Students with the very lowest and highest academic potential are the least affected by neighbourhood disadvantage, while those with below average—but not at the lowest end—are most strongly affected. Moreover, while girls are less affected than boys, and children from less educated and affluent families are more affected by neighbourhood disadvantage than their more privileged peers, the effects of these observed moderators are considerably smaller than the heterogeneity observed as a function of academic proneness. Overall, our use of quantile regressions opens up new venues for understanding ‘for whom’ neighbourhoods matter, with individual-level academic vulnerability and strengths being an influential source of neighbourhood effects variation.