Diverticular disease is one of the most common causes of outpatient visits and hospitalisations across Australia, North America and Europe. According to the Gastroenterological Society of Australia , approximately 33% of Australians over 45 years of age and 66% over 85 years of age have some form of colonic diverticulosis. Patients with colonic diverticulosis are known to develop subsequent complications such as acute colonic diverticulitis (ACD), and when more than one attack of diverticulitis occurs, there is a 70‐90% chance that the individual will experience ongoing problems and recurring infections throughout their lifetime. Medical imaging is fundamental in the diagnosis, treatment and ongoing management of ACD and its complications, with Computed Tomography (CT) identified as the prevailing gold standard in the last few decades. Cross‐database searching highlighted a large gap in the literature regarding the effectiveness of Magnetic Resonance Imaging (MRI) as a non‐ionising radiation alternative imaging tool for ACD imaging after the mid‐2000s, despite ongoing technological advancements in this modality. This narrative review identified 13 key publications  that evaluate MRI for ACD imaging, of which five were published within the last decade. Several existing MRI protocols are deemed suitable for ACD imaging, and it is recommended they be re‐evaluated in larger cohorts. Future studies should consider the rapidly growing technological improvements of MRI, its cost efficiency and its applicability in modern day healthcare settings when addressing ACD management. This is especially important considering the gradual rise in radiation dose among the Australian population attributable to increased CT referrals, alongside increased reporting of ACD cases in younger individuals. Diverticular disease is one of the most common causes of outpatient visits and hospitalisations. Cross‐database searching has highlighted a large gap in the literature: an absence of publications providing efficacy data on Magnetic Resonance Imaging (MRI) as a non‐ionising radiation alternative for ACD. This narrative review aims to explore available published data and provide an up‐to‐date evaluation of MRI as a tool for the diagnosis and ongoing management of ACD. Diverticular disease is an umbrella term for a spectrum of conditions associated with diverticulosis which are small, pressure‐induced herniations (diverticula) at points of weakness within the mucosal and submucosal lining of the digestive system.Diverticulosis of the colon is traditionally described as an age‐related disease, seen in approximately 33% of Australians over 45 years of age and in 66% of Australians over 85 years of age.Diagnosis of colonic diverticular disease and ACD requires a combined assessment of clinical signs, biomarkers and imaging studies. The current preferred imaging modality is Computed Tomography (CT). CT enables accurate assessment of intraluminal and extraluminal components of the disease and the involvement of nearby organs. However, in the last two decades, concern has grown over increased radiation dose attributable to CT, along with the associated increased risk of cancer.Magnetic Resonance Imaging (MRI) is a non‐ionising imaging alternative to CT. During the late 20th and early 21st century, many publications assessed MRI use for ACD. However, following the establishment of CT as the gold standard imaging modality for lower abdominal pain,Increased cases of ACD worldwide, particularly in younger individuals, combined with the need for repeat imaging of recurrent infection events, suggest a need to re‐evaluate the appropriateness of MRI versus CT. In light of continual and rapid technological advancements and patient needs, this narrative review aims to explore available published data and provide an up‐to‐date evaluation of MRI as a tool for the diagnosis and ongoing management of ACD. Patient comfort, financial expenses and the overall burden of MRI on medical imaging departments will also be considered when defining its future feasibility.A narrative literature review was deemed most appropriate to provide a broad perspective of the existent knowledge on MRI use in the diagnosis and management of ACD, given the lack of data available to inform a detailed meta‐analysis. A literature search was conducted in four databases, Scopus, Embase, MEDLINE and CINAHL, using boolean combinations of keywords such as ‘MRI’, ‘magnetic resonance imaging’, ‘diverticul*’, ‘colon*’, ‘large intestine’ and ‘large bowel’. The inclusion criteria were studies published in the English language, focusing on human adult participants of all genders and ages, with or without pre‐existing conditions. Studies focusing on diverticular disease outside the large bowel were excluded, as were paediatric studies, which predominantly focused on Meckel’s diverticula of the small bowel. The search was limited to publications within the last 20 years (2000–2020).The Preferred Reporting Items for Systematic Reviews and Meta‐Analyses (PRISMA) was appropriated to inform the selection process of literature Fig. . Upon re‘Might be Appropriate’ as an imaging procedure for initial examination of left lower quadrant pain and suspected diverticulitis.One of the salient advantages of MRI over CT and ultrasound (US) is its superior soft tissue resolution,Five studies published in the last decade build upon existing data and, in particular, highlight the improvements in non‐contrast MRI techniques for detecting ACD pathology.Although the approach tested by Heverhagen and colleaguesTwo of the primary papers identified in this literature review, Heverhagen et al.2.As with all contrast‐enhanced MRI, gadolinium use can be contraindicated in patients presenting with acute renal failure, chronic kidney disease or an estimated glomerular filtration rate below 30 ml/minute/1.73 mMultiple studies show promising results from non‐contrast MRI protocols for initial investigation of suspected ACD in patients presenting with lower left quadrant pain.While an in‐depth analysis of MRI protocols is beyond the scope of this review, the value of DWI sequences in the imaging of ACD deserves mention. Formerly used for oncological procedures and highlighting neoplastic processes, DWI protocols create contrast dependant on the Brownian movement of water molecules within tissue. The produced signals of tissues exhibiting cellular swelling/restricted diffusion are depicted as hyperintense signals on scans. DWI allows for improved detection of oedema, abscess formation and inflammatory lesions, which suggests a potentially high sensitivity for colonic diverticulitis.In the last few decades, numerous techniques have evolved to overcome the long‐standing challenges posed by intraluminal gas and peristaltic motion of abdominal structures in MRI imaging. Smooth muscle relaxants such as Butylscopolaminiumbromid (Buscopan) have been administered in a number of studies Table  at a dosAdditionally, Byott and HarrisA recent review by Serai et al.Despite improvements in technology and efforts to address the challenges of MRI, limitations persist which prevent its use from superseding CT as the gold standard for ACD imaging.The radiographer first and foremost has a duty of care towards the patient during image acquisition. A positive patient experience depends heavily on appropriate management of the patient’s emotional and physical states. Proper patient communication and preparation are particularly important for MRI scanning to ensure patient compliance and mutual understanding of the imaging procedure. Advancements in rapid acquisition single shot sequences coupled with post‐processing algorithms have demonstrated shortened scan times and address limitations of claustrophobia and motion artefacts, thereby improving patient experience and image quality.Despite MRI advancements to improve patient comfort and satisfaction, a prevailing impediment to its wider use in medicine and patient access is the relatively large out‐of‐pocket expense compared to that of CT and US. In Australia, numerous MRI examinations are excluded from the Medicare Benefits ScheduleThe inability of MRI to facilitate interventional techniques (biopsy and drainage) is considered to be another significant drawback. Current literature and clinical practice predominantly recommend two methods for the treatment of diverticular abscesses: antibiotic therapy, prescribed for phlegmon/abscesses less than 4 cm in diameter, or treatment by drainage if larger than 4 cm, performed under US or CT guidance.The implementation of MRI also burdens imaging departments with the need for further training of radiographers in this modality. This is due to the additional technological expertise required to perform MRI examinations. MRI radiographers must be able to interpret pathology and competently manipulate scan variables, which depend on both physical and biochemical parameters to differentiate between soft tissue pathologies.The clinical efficacy and diagnostic accuracy of MRI in the context of ACD remain unclear. The reasons are three‐fold – firstly, current evidence supporting the relationship between the severity of ACD and the diagnostic accuracy of MRI protocols is scarce. Secondly, pitfalls in the current literature on MRI are largely attributed to small prognostic inception cohorts at early stages of the disease and lack longitudinal data from follow‐up imaging. Thirdly, there is an absence of cross‐population representation with studies displaying low external validity due to the use of small homogenous inception cohorts, with the majority of data acquired from patients with sigmoid diverticulitis. Findings from the published studies included in this review provide low to moderate evidence for MRI as a diagnostic tool in favour of CT and US for ACD imaging.Future investigations should focus on looking at the economic feasibility of MRI in clinical practice. It would be advantageous to have professional bodies such as The Royal Australian and New Zealand College of Radiologists (RANZCR) investigate MRI use in ACD for potential establishment of protocols and associated healthcare expenses. Ultimately, the potential of MRI in future clinical practice should be empirically driven. This potential will ultimately be determined by two key issues: firstly, the ability to reduce image acquisition time to improve motion‐related artefacts, by taking advantage of the intrinsic contrast properties of the underlying pathological changes to minimise the need for gadolinium enhancement; secondly, the success of implementing protocols that focus on improving costs and service availability to patients through the Medicare Benefits Scheme.This narrative review investigated the current and potentially growing role of MRI in the diagnosis and ongoing management of patients with ACD. MRI offers consistent imaging performance, with the added benefits of modern cross‐sectional imaging without the burden of ionising radiation. This review highlights the unavailability of research into MRI for ACD imaging, with only a few clinical papers produced in the early 2000s, and even fewer after 2010. While it appears that CT prevails as the modality of choice for ACD, the current review highlights the potential of recently developed MRI techniques as alternatives. Based on the literature analysis, the authors encourage the scientific community to continue exploring the potential of MRI for ACD management and as a diagnostic tool in populations affected by ACD, especially younger patients. This will support evidence‐based practice and encourage practitioners to take advantage of opportunities where non‐ionising imaging techniques can be used. Randomised prospective trials evaluating MRI against CT as a diagnostic standard would be particularly helpful in guiding the appropriate choice of imaging for evaluating ACD in future.The authors declare no conflict of interests regarding this literature review.


The aim of this study was to evaluate the differences in surgical capacity for head and neck cancer in the UK between the first wave (March‐June 2020) and the current wave (Jan‐Feb 2021) of the COVID‐19 pandemic.REDcap online‐based survey of hospital capacity.UK secondary and tertiary hospitals providing head and neck cancer surgery.One representative per hospital was asked to report the capacity for head and neck cancer surgery in that institution.The principal measures of interests were new patient referrals, capacity in outpatients, theatres and critical care; therapeutic compromises constituting delay to surgery, de‐escalated surgery and therapeutic migration to non‐surgical primary modality.Data were returned from approximately 95% of UK hospitals with a head and neck cancer surgery specialist service. 50% of UK head and neck cancer patients requiring surgery have significantly compromised treatments during the second wave: 28% delayed, 10% have received radiotherapy‐based treatment instead of surgery, and 12% have received de‐escalated surgery. Surgical capacity has been more severely constrained in the second wave (58% of pre‐pandemic level) compared with the first wave (62%) despite the time to prepare.Some hospitals are overwhelmed by COVID‐19 and unable to offer essential cancer surgery, but all have neighbouring hospitals in their region retaining good  capacity. It is noteworthy that very few patients have been appropriately redirected away from the hospitals most constrained by their burden of COVID‐19. The paucity of an effective central or regional strategic response to this evident mismatch between demand and surgical capacity is to the detriment of our head and neck cancer patients. As a consequence of these constraints, as well as concerns over cross‐infection with SARS‐CoV‐2, HN surgery was minimised, de‐escalated or avoided in many centres.A severe second wave of COVID‐19 during winter 2020/21 was indeed widely predicted, even during the first wave.The aim of this study was to evaluate the differences in surgical capacity for head and neck cancer in the UK between the first (March‐June 2020) and the current (Jan‐Feb 2021) COVID‐19 pandemic waves. Further, we report on efforts in strategic planning and mutual aid between hospitals.2REDCap (Research Electronic Data Capture) was employed to record all data through its web application. A 13‐item survey questionnaire Appendix  was cons3A confidential survey was distributed electronically to existing COVIDSurg‐HN collaborative members, a wide group which had collected in excess of 5000 head and neck cancer treatments carried out during March‐June 2020.4The survey period was from 1 to 7 February 2021. Respondents were requested to complete the survey with estimates of HN cancer service capacity at three distinct timepoints:prior to the COVID‐19 pandemic.during the first peak of COVID‐19 infection (March‐June 2020).during the current peak of COVID‐19 (January‐February 2021).The entry fields represented either percentage estimates, defined response criteria or direct yes/no responses. In all instances, these responses were classified as required fields to complete the survey. Data collected included the geographical location of the hospital, access to operating lists, face‐to‐face versus virtual outpatient clinic attendance and degree of access to critical care beds following HN cancer surgery. Data were collected regarding operating capacity at alternative hospital sites, and if so whether surgery performed by a differing surgical team. We ascertained the extent of delay to HN cancer surgery beyond 62‐day rule, surgical de‐escalation and therapeutic migration away from primary surgery. No specific reporting guideline was followed.5Data were obtained from 73 individual returns but were incomplete for one hospital. Ten hospitals had (understandably) entered duplicate data given the multiple channels of communication employed. In most cases, the duplicate data returned were very closely matched and for others represented a difference in caseload between the ENT and OMFS surgeons entering their own data, so a crude mean of the two data entries was employed in these cases. By comparison with the DAHNO list5.1Estimates of HN cancer referrals are currently (Jan‐Feb 2021) on average, at 85% of pre‐pandemic levels (range 35%‐120%) compared with mean 61% (range 20%‐100%) during the first wave in March‐June 2020. Notably, 5 of the 62 (12%) units report an even higher current caseload than prior to the COVID‐19 pandemic, a feature not apparent in the first wave in any centre. Theatre capacity was slightly lower in the second wave, estimated as a mean 58% (Jan‐Feb 2021) versus 62% (March‐June 2020) of pre‐pandemic levels. Outpatient appointments carried out face‐to‐face increased to a mean 65% during the second wave, from a mean 46% in the first wave and 98% prior to the pandemic. 26% of HN surgery teams have had no access to critical care beds during the second wave, and 42% have substantially reduced access. Comparable data for the first wave are 15% and 44%, although this is in the context that the majority of hospitals  reporting occasional difficulty in obtaining critical care beds for HN cancer patients prior to the pandemic. In the second wave, 30% of HN teams have had at least some access to other hospital sites to alleviate pressure from their “usual” hospital site, although in only 11% has this required transfer of patient care for surgery to be performed by another team. This has remained consistent throughout differing periods of the pandemic, with comparable data for the first wave being 40% and 10%, respectively. Surgery has been delayed in a mean 28% of HN cancer patients during the second wave, very similar to 30% in the first wave. Pre‐pandemic delay was only 6% on average. A switch in therapeutic modality away from primary surgery is reported in 10% of second‐wave cases, and surgical de‐escalation in 12% second wave, compared with 20% and 17%, respectively, during the first wave.5.2normal” > = 100% pre‐pandemic theatre capacity , “reduced” > = 50% and <100% ; “greatly reduced” <50% . These data are summarised in Table Hospitals were categorised by current operating theatre capacity for HN cancer: “5.3UK hospitals were categorised geographically into 10 regions, and their data comparing the impact of surgical capacity on therapeutic compromise are presented in Table 6These data show that surgical capacity to treat HN cancer has again been severely impacted during the second wave of COVID‐19 during January and February 2021. The extent of its impact is broadly comparable to the first wave, with one‐third of hospitals with greatly reduced theatre capacity, a quarter with zero access to postoperative critical care. Overall, half of HN cancer patients requiring surgery have compromised treatments. The national and regional average data, however, obscure important and even more troubling detail. A minority of hospitals have been completely overwhelmed by patients suffering with COVID‐19 such that they are unable to offer any meaningful HN surgery despite recovering referral pathways and resultantly increasing case demand. Unfortunately, the NHS has not prepared for redirection of patients away from such hospitals where, as a result, the compromises to effective and timely therapy are most significant.This study has been conceived, data have been collected, cleaned and analysed, written, peer‐reviewed and pre‐published within a 2‐week window. The penetration to UK HN surgery centres has been greater than 95%, and colleagues have returned data irrespective of regional or specialty allegiances. Once again, the medical profession has stepped up to the challenges of COVID‐19 and rapidly established new ways to work and collaborate, as amply demonstrated by the COVIDSurgIt appears that the UK second COVID‐19 wave is somewhat more severe than the first, as evidenced by daily announced death rates reaching 1820 early in 2021,Despite 6‐month preparation time between the waves, half of cancer treatments have been significantly compromised during the second wave . Transfer of care to other teams remains uncommon. The 10% figure reflects data per hospital and presumably translates into a rather lower percentage of individual patients actually being transferred. Surgeons moving their service to operate at another site is a common mitigation in first and second wave and presumably reflects use of the private sector or mutual aid from “cold” sites. Of note, surgeons were only half as likely to accept de‐escalation 20% vs 12%, similarly less likely to accept therapeutic migration 17% vs 10%, during the second wave. As intuition would predict, units with most severely affected surgical capacity also experience the greatest extent of therapeutic compromise . For a third of hospitals treating HN cancer, their greatly reduced capacity reflects a major detrimental effect on cancer treatment, with likely significant consequent implications for mortality. Critically, hospitals with most severely constrained surgical capacity all do appear to have neighbouring units in the same region maintaining good or near‐normal capacity, but this has unfortunately not translated into widespread transfer of patients.and the authority to implement redistribution of cancer cases for best interests of our patients: cancer alliances, NHS trusts, national associations? It is not clear to what extent is HN surgery typical of all surgical oncology in this respect. HN surgery has a particularly onerous requirement for airway skills, specialist nursing and professions allied to medicine and bulky, expensive and fragile specialist equipment such as microscopes, plating kits, lasers and robots. This makes moving away from COVID‐19 affected sites logistically complex. It is also possible that some surgeons make such a personal interconnection with their patients early in their care pathway, that there may be a cultural resistance to accept another team could achieve similar results, and a consequent reluctance to refer on. Conversely, patients may also choose to remain with a team they have met or have difficulty travelling to a hospital further afield.In the UK, the lead time to prepare for this second wave was around 5‐6 months, and with the National Health Service under central strategic control, it was presumably plausible, and certainly highly desirable, to optimise the available resources. This would have minimised consequent rationing of, and delay to, primary surgery for HN cancers. Since the start of the pandemic, international and UK experience has repeatedly shown that the major impacts of COVID‐19 fall disproportionately upon certain regions and at certain times. Anecdotally, one major UK HN unit has been hosted by a hospital burdened by more than 1000 inpatient beds taken by COVID with 200 of them ventilated. Where this impact coincides with a large volume HN surgery centre, perhaps redirection of patient pathways could be very effective and should be deployed. The mismatch between supply and demand appears to be severe in a significant minority of hospitals but has not yet been properly addressed at a central strategic level, perhaps reflecting lack of capacity and authority to implement such decisive actions. Which bodies have both the required data These issues reveal considerable fragility within the NHS, where life‐critical but elective services can apparently be so vulnerable to acute emergency pressures. This lack of resilience in elective care is often seen to a lesser extent as “winter pressures,” but not nearly as severely as in the current second COVID‐19 wave. The lack of national strategic response is of great concern, but it is perhaps not yet too late to act. The “bow wave” of delayed HN cancer cases remains ahead of us and many more months of COVID‐19 restrictions remain.The authors have no conflicts of interest to declare.No ethical approval was obtained as confidentiality of responders / hospitals, and anonymity of data presentation was maintained. Other than encouragement to contribute to better understanding of the impact of COVID‐19 on Head & Neck services, there were no incentives to respond. The authors have no conflicts of interest to declare.Supplementary MaterialClick here for additional data file.Supplementary MaterialClick here for additional data file.


Research on women's experiences of infant feeding and related moral discourse suggests that self‐conscious emotions may be highly relevant to breastfeeding support interactions. However, the emotional impact of receiving support has not been fully explored. The aim of this review is to re‐examine qualitative UK research on receiving breastfeeding support, in order to explore the role of self‐conscious emotions and related appraisals in interactions with professional and peer supporters. From 2007 to 2020, 34 studies met criteria for inclusion. Using template analysis to identify findings relevant to self‐conscious emotions, we focused on shame, guilt, embarrassment, humiliation and pride. Because of cultural aversion to direct discussion of self‐conscious emotions, the template also identified thoughts about self‐evaluation, perceptions of judgement and sense of exposure. Self‐conscious emotions were explicitly mentioned in 25 papers, and related concerns were noted in all papers. Through thematic synthesis, three themes were identified, which suggested that (i) breastfeeding ‘support’ could present challenges to mothering identity and hence to emotional well‐being; (ii) many women managed interactions in order to avoid or minimise uncomfortable self‐conscious emotions; and (iii) those providing support for breastfeeding could facilitate women's emotion work by validating their mothering, or undermine this by invalidation, contributing to feelings of embarrassment, guilt or humiliation. Those supporting breastfeeding need good emotional ‘antennae’ if they are to ensure they also support transition to motherhood. This is the first study explicitly examining self‐conscious emotions in breastfeeding support, and further research is needed to explore the emotional nuances of women's interactions with supporters. Experiencing and managing self‐conscious emotions is part of infant feeding for many women, but this is underresearched.Engaging with breastfeeding support can challenge women during their transition to motherhood, evoking further self‐conscious emotions.Women may manage interactions with breastfeeding supporters carefully to minimise uncomfortable self‐conscious emotions and maintain a positive mothering identity, and this sometimes reduces the effectiveness of support.Breastfeeding supporters can significantly impact  women's development of a positive mothering identity. They need good emotional ‘antennae’, as self‐conscious emotions are often hidden.1Those promoting breastfeeding have sometimes been accused of promoting guilt among women who formula feed . Breastfeeding support could be the main focus of the study or part of a broader investigation, such as experiences of general postnatal support or experiences of breastfeeding. Asynchronous online support via social media was not included, though telephone support was.The search was conducted systematically using five electronic databases: CINAHL, Scopus, MEDLINE, PsychINFO and PubMed. Search terms included (Breastfeeding OR breast feeding OR breast‐feeding OR lactation OR breastfeed*) AND  AND . Limits were applied for English language and to retrieve peer‐reviewed publications. We searched for UK studies from January 2007, following a rigorously conducted meta‐synthesis of women's experiences of breastfeeding support . Studies were excluded if they only reported health professionals' perspectives or analysed data from a previously published study. Quality appraisal of each paper was carried out by one of the research team, and reviewed by another team member, using a checklist devised for the study. This enabled assessment of each paper against the following criteria for inclusion: appropriate and clearly reported recruitment and data collection procedures; ethical approval; sufficient in‐depth qualitative data from mothers to provide insight into experiences of receiving breastfeeding support; and clear accounts of coding procedures, with sufficient quotes to justify and illustrate themes. As the aim was to reanalyse previous findings through a novel conceptual lens, studies were not rejected if the original analysis was mostly descriptive, with limited theoretical development, providing the data shed light on women's experiences of receiving support with breastfeeding and had been collected and reported in a rigorous and transparent manner. Due to the paucity of research on self‐conscious emotions when receiving support, and the often hidden nature of these experiences, it was important not to exclude otherwise trustworthy studies unnecessarily. Figure 2.3We were mindful of Scheff's  argument2.4a priori themes within a coding template that was revised and expanded in response to the data. Template analysis was originally developed for thematic analysis of primary data though there are some examples of its use for qualitative synthesis . These themes were developed through exploration of issues relevant to self‐conscious emotions, such as thoughts and feelings concerning self‐evaluation, exposure in front of breastfeeding supporters, perceived judgement by others involved in feeding support and management of emotional feelings in relation to these issues. Cultural aversion to direct discussion of many self‐conscious emotions means that these concerns are sometimes the only indicators of fleeting self‐conscious emotions or avoidance of these.The relevance of self‐conscious emotions to breastfeeding support was confirmed across the papers. Emotional aspects of receiving support were more apparent in studies that focused primarily on women's experiences, rather than evaluation of an intervention or care context. However, even if briefly, all papers included material relevant to our broad conceptualisation of self‐conscious emotions. Below, we begin with an overview of direct references to specific self‐conscious emotions. This is followed by discussion of the final themes from the template analysis , developed through the stages of the template analysis, suggested that obtaining support with breastfeeding involved interactions that could present multiple challenges to the self. Identity as a breastfeeding mother could be precarious, with the possibility of guilt, shame and embarrassment hovering on the periphery of many women's experiences, and more central for some. Many women appeared to engage in active management of their emotions while interacting with maternity care services, in order to maintain an intact self and avoid uncomfortable self‐conscious emotions. Those supporting breastfeeding could facilitate this emotion work where mothers perceived them as validating their mothering. Alternatively, ‘support’ could be experienced as invalidating and undermining.Three overarching themes  She's not managing very well  reflecting back a positive view of the woman and her mothering and (ii) meaningful connection and acceptance.I would be like, ‘I can't do it, I can't do it’ and I would go back thinking ‘I'm going to tell them I can't do it’ and they would make me feel better again …  (Thomson & Dykes, Similar experiences were reported elsewhere (Beake et al., make you doubt yourself’ (Thomson & Crossland, Women also complained of being disrespected as autonomous adults through pressure to make infant feeding decisions, dismissal of their ideas, judgemental surveillance or infantilisation (Condon et al., Task‐based, routinised care, during which the young women were treated as objects rather than self‐determining individuals … (see also Taylor et al., Some women described more subtle forms of invalidation where they felt uncared for because staff seemed disinterested in their needs or unavailable (Fraser et al., 3.5.3invalidation in order to struggle with an absence of validation and reassurance, and the emotional consequences of this.The first two themes illustrated how some women approached motherhood and infant feeding feeling under surveillance and expecting to be judged by maternity care workers, particularly if not breastfeeding. Taylor et al.  linked t4This was a focused synthesis, exploring self‐conscious emotions, and was not an attempt to capture all aspects of women's experiences of receiving breastfeeding support discussed in the original papers. However, the review clearly suggests that self‐conscious emotions and related self‐appraisals, particularly negative ones, are relevant to many UK women's experiences of varied types of breastfeeding support. Though women may not always discuss these emotions explicitly in interviews, or experience them strongly, many women can find their mothering identity precarious and in need of active management when interacting with supporters. Careful emotion work is required to avoid feeling guilt, shame, embarrassment or even humiliation. As indicated in a recent review (Russell et al., The review focused on the United Kingdom. However, findings are likely to be transferable to contexts with similar breastfeeding support services and where cultural messages around infant feeding mean women approach breastfeeding support with a similarly conflicted view of themselves as breastfeeding mothers. This review supports Thomson et al.'s  conclusican also foster pride and a sense of achievement. However, although there was strong evidence of women internalising perceived inadequacies with infant feeding as failure, there were comparatively few examples of positive infant feeding experiences being internalised as a personal success.Although some women primarily approach breastfeeding support for help with practicalities, or require little support, the review demonstrates that others can receive far more from ‘breastfeeding’ interventions than help with successful breastfeeding. Positive validation can help to counter negative self‐beliefs and support women in developing a positive mothering identity that is resilient to shame, guilt and embarrassment. Positive relationships with others Unfortunately, a number of women in the papers reviewed had experienced aspects of breastfeeding support as undermining and invalidating. Therefore, ‘support’ sometimes seemed risky and some women's apparent strategies for managing this risk—selective engagement and withdrawal, ‘illusions of compliance’ or externalisation of blame—can reduce the likelihood of receiving appropriate advice and of validating relationships with health care providers. Responses of self‐denigration were also apparent across several papers, which, in some situations, may increase the risk of mental health difficulties postnatally (Dunford & Granger, 4.1It is time to stop laying the blame for the UK's low breastfeeding rates in the laps of individual women and instead acknowledge that this is a public health imperative for which government, policy makers, communities and families all share responsibility (UNICEF UK, Attempts to shift the moral and hence emotional landscape of infant feeding in the United Kingdom are already underway and have focused on ‘changing the conversation’:rights to breastfeed (Trickey, This is one of the most useful ways in which public discourse around breastfeeding could change. It reduces blame, shame and guilt, while targeting key environmental influences on breastfeeding such as social discourse and availability of support and can further empower women by emphasising the protection of their Trickey, . ChallenTrickey, . InsteadTrickey,  to womenTrickey, . NonetheTrickey, , and it Trickey, .There is increasing recognition of the importance of respectful conversations with mothers about infant feeding, which are empathic, person‐centred and non‐judgemental (e.g., Schmied et al., 4.2how breastfeeding support is experienced by different women within different relationships and contexts is as important as researching what works, when ‘what’ is defined in broad brush terms as a packaged intervention. In‐depth ethnographic examination of how the cultural or organisational context shapes support relationships and behaviours might also enable better understanding of how some postnatal inpatient settings foster invalidating interactions whereas others foster validation. Gibson (Further research into the emotional impact of breastfeeding support interventions might help to shed light on the question raised previously as to why particular breastfeeding support interventions may be successful sometimes, but not others (e.g., Hoddinott et al., . Gibson  notes ho4.3felt by women in the context of receiving breastfeeding support, how this can shape their interactions with health care providers and how these interactions can be rethought to ensure they support mothers and protect breastfeeding.By beginning with a clear conceptual framework for our synthesis, we offer a new lens on breastfeeding interventions. This does mean that our approach draws attention to some issues rather than others. However, these issues may often be hidden and underresearched due to their taboo nature. This is the first review to explore the role of self‐conscious emotions in breastfeeding support. However, it should be seen as opening an area for further research rather than offering a detailed examination of emotion processes. We used a broad conceptualisation of self‐conscious emotions, focusing on accounts of self‐evaluation and concern about one's worth in the eyes of others, whether or not emotions were mentioned explicitly. Our aim was to include experiences where self‐conscious emotions might be on the periphery of consciousness but avoided through careful self‐management. This approach was important given the cultural preference for indirect references to some self‐conscious emotions, the assumption that unacknowledged self‐conscious emotions can still profoundly shape interactions Scheff,  and the The authors declare that they have no conflicts of interest.Approval for this review was not required by the institutional ethics panel as the findings in the papers reviewed were already in the public domain and ethical approval had been obtained by the original researchers.DL and JM designed the study. JM and SH conducted the searches. DL, JM and SH coded and analysed the data. DL designed the original template and audited the final analysis. DL wrote the initial draft of the paper. DL, JM and SH reviewed and edited the paper and approved the final manuscript.


We have recently conducted and published a bibliometric analysis of research on OC that covered 118 years for the first time in Morocco ) studies that aims to develop clinical research on OC for the first time in Morocco. Our main goal is to implement research in OC based in our country, expected to enhance clinical research in this neglected area. Our vision  encompasStep 1 (2017–2022): Planning the Rationale and Training the Local Oncology Workforce–Conducting a bibliometric analysis of the national scientific production on OC (as commented).–meta-analyses on emerging topics in gynecologic oncology with a particular focus on OC.Promoting the publication of books, reviews, and systematic reviews and –Medline-indexed journals to foster international collaboration and increase the visibility of national oncologists.Preparing special issues for international –Initiating OVANORDEST-1 study: a retrospective study that is expected to provide the rationale for future prospective studies. The cohort will collect data from archived patients’ files to present an overview of epidemiology, clinic-pathologic patterns, and survival outcomes of women with OC. It will also investigate various inexpensive and potential prognostic and predictive markers for OC. This would be the first study of this type, and is intended to support cancer registration, and real-life data.–ESMO, ESGO, IGCS, and ASCO, and others.Supporting oncology residents to develop expertise in the management of OC through multidisciplinary team meetings, fellowships and participation in masterclasses of international societies such as –Training the workforce of local oncologists to conduct research in medical oncology.–Building partnerships with the “Institut de Recherche sur le Cancer”.–Improving the role of women oncologists in clinical research on OC to limit gender inequality and increasing the visibility and engagement of junior female researchers on OC.–Developing a working group on cancer biomarkers to develop national and international collaborations on OC.–Global Ovarian Cancer Charter.Joining international initiatives and coalitions on OC such as Step 2 (2023–2026): Development and Implementation of Prospective Clinical Research and Publishing Excellence–Initiating OVANORDEST-2 study: a prospective observational trial to validate the findings of our earlier feasibility study and provide high-quality data for biomarker research with prior hypothesis testing.–Organizing an annual best research article award and conferences on OC, summer schools, and masterclasses on research methods in oncology.–Supporting national innovative cancer research projects on OC.–Moroccan Society for Ovarian Cancer (MSOC) and development of a Moroccan oncology journal with an international publisher.Foundation of the –Enhancing policy formulation and aid decision-makers to appropriately invest in OC in Morocco and address evidence-based unmet needs.–Mentoring undergraduate medical students to encourage them to pursue a career in medical oncology and clinical research and establishing paid research internships for PhD and MD students at our department of medical oncology.–Raising awareness and empowering patients’ advocacy for OC in Morocco.–Conquer Cancer Foundation.Exploring funding opportunities of international organizations such as the –Building partnerships with international societies to set up fellowship programs in surgical oncology and gynecologic oncology for Moroccan young general surgeons and gynecologists to develop expertise in OC management.Step 3 (2027–2030): Maintaining Excellence Toward a Research Focusing on Patients’ Outcomes–Initiating OVANORDEST-3 study: development and prospective validation of an inexpensive score for prognostic classification of OC patients.–Moroccan Institute for Ovarian Cancer (MIOC): a national hospital and institution that is expected to deliver precision medicine and best of care to Moroccan women with OC, as a national and regional reference hub. The institute will also conduct clinical trials and translational research.Foundation of the –Launching a Moroccan multicenter randomized and controlled clinical trial on OC.–Maintaining clinical research and delivering improved supportive care for OC patients.https://www.springer.com/gp/book/9789811618727), one umbrella systematic review (To date, we could prepare two journal special issues, a book, review articles (c review , and sevThe authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.


Eighty‐one percent of the households living close to the forests perceive that forest is a threat to their survival. Overall, our results imply that strategies need to be sought in order to minimize the socio‐ecological impacts of crop raiders mainly in locations close to forest edges.Crop raiding is a major form of human‐wildlife interaction mainly in the ecotone areas of human‐modified natural landscapes. The aim of this study was to examine the spatial pattern of crop raiding and the resultant impacts on how farmers perceive forests at different distances from Yayu Coffee Forest Biosphere Reserve which is located in southwest Ethiopia. For this, thirty transects (each 1 km long) were laid out at 200 m interval parallel to forest edges: ten transects close to forest (<0.5 km), ten at intermediate (0.5–1 km), and ten transects were taken far from forest (>1 km). Along each transect, 2–6 households were randomly selected and interviewed using semistructured questionnaire. The perception of the respondents on forests at different distances from forest edges was analyzed using Pearson's Chi‐square test. The variation in the amount of damage among these three locations was tested using one‐way ANOVA. Four wild large mammals including olive baboon, vervet monkey, bush pigs, and crested porcupine were identified as top crop raiders in the area. The frequencies of occurrence of crop raiders decreased with increasing distance from forest edges. Similarly, the amount of damage in maize fields was higher close to forests when compared with that of either at intermediate or far from forest edges ( Crop raiding is decreasing with increasing distance from forest edges. The amount of damage in maize fields was higher close to forest edges Households living close to the forests perceive that forest is home for wild animals and a threat to their survival. Such phIn managing the human‐wildlife conflict, the attitude of the local inhabitants needs to be critically understood within temporal and spatial context, for instance, in areas where humans live adjacent to natural habitats and interaction often exists between humans and wild animals  were arranged with 200 m interval in parallel to the first transect and to each other in the agricultural landscape. These transects were categorized into three locations: ten transects close to forest (<0.5 km), ten intermediate (0.5–1 km), and ten transects far from forest (>1 km) in similar method used by Lemessa et al. . By walkAfaan Oromo were collected during the questioner survey  was tested using Pearson's Chi‐square test. The number of maize stems attacked by crop raiders was used as a proxy indicator for the amount of damage by crop raiders. The number damaged maize stems were square‐root transformed to meet the assumption of homoscedasticity of the variance. To test for the variation in the amount of damage among the three locations  one‐way ANOVA was run and after the significant variation was found among the three locations, a multiple comparison of the means was made using HSD Tukey test with bonferroni 33.1Papio anubis), vervet monkey (Chlorocebus aethiops), bush pig (Potamochoerus larvatus), and crested porcupine (Hystrix cristata) were identified by all of the respondents as the worst crop raiders in the area. According to the respondents, the crops that are most raided by these and other wild large animals are maize, sorghum, potato, mango, avocado, and teff. In this connection, the respondents close to forests (67%), at intermediate distance (34%), and the respondents at far away from forests (42%) mentioned that from among the crops identified above, maize is reported as the most liable crop to be raided by wild large mammals in the area . The households close to the forests face severe crop raiding impact than those living far away from Yayu Coffee Biosphere Reserve. Here, the respondents living close to forests (89.6%) and at intermediate distances from forests (28.9%) estimated that the annual maize yield loss due to crop raiding ranges between 20% and 40%, while 100% of the respondents dwelling at far away from forests indicated that the annual maize is <5% , at intermediate distance from forests (65.8%), and respondents situated at far away from forests (52.6%) of, explained that forest is home for wild large mammals and hence is a threat to our survival Table . However4Understanding how crop raiding varies across spatial scales from forest edges is critically essential in subsistence farming system to frame harmonized development‐conservation schemes. We show that the pattern of crop raiding and perceptions toward forest vary with distances from forest edges. The frequencies of crop raiding by wild large mammals surrounding Yayu Coffee Biosphere Reserve in southwest Ethiopia decrease from forest edges and flatten after 2 km. Similarly, the level of crop damage is higher at sites close to forests and at intermediate distances from forests when compared with the sites at far away from forests. Our results corroborate several previous findings from southwest Ethiopia that the frequency of occurrence of wild mammal crop raiders and the corresponding extent of crop damage decrease with increasing distances from forest edges into agricultural fields  of the farmers estimated the annual maize yield loss due to the crop raiders to be between 20% and 40%, per hectare close to forests and 28.9% (11) at intermediate locations and none of the respondents reported at far away from forests Table  who measThe spatial variation in the resultant impacts of the crop raiding is reflected on how farmers perceive forests. In view of this, about 81% of the respondents dwelling close to forest perceive that forests host wild animals that are threat to their life while 47.4% of the respondents located at far away from forests explained that forests are useful for their life Table . Such heOur results depicted that maize is the most raided crop at different distances from forest edges and according to our respondents the reason for this might be maize is sweet and more palatable compared to other crops. As regards this, the study conducted in Uganda stated that baboons prefer maize for raiding throughout the year when it is available in agricultural fields relative to other crops Hill, . Unequiv5Crop raiding triggers a human‐wildlife conflict mainly in the ecotone areas of human‐modified natural landscapes. Understanding the spatial pattern of crop raiding from forest edges is critically essential in subsistence farming system to frame harmonized development‐conservation schemes. The present study showed that the intensity of crop raiding and how farmers perceive forests vary with distances from forest edges. In sum, our results suggest that strategies need to be sought in order to minimize the socio‐ecological impacts of crop raiders mainly in locations close to forest edges.None declared.Alemayehu Mamo: Data curation (lead); Project administration (lead); Writing‐original draft . Debissa Lemessa: Formal analysis (lead); Methodology (lead); Validation (lead). Obsu Hirko Diriba: Funding acquisition (lead); Supervision ; Writing – review and editing . Debela Hunde: Supervision ; Validation ; Writing – review and editing .This study is based on the questionnaire survey and observation or assessment of the crops damaged by large mammal pests and did not involve human subjects, experimentation with animals or collection of specimens. We all authors abide by the Ethical standards stated in the Ecology and Evolution journal Guidelines for Authors.


Meaningful student–instructor interactions during an undergraduate degree course can have important effects on student learning. The format by which those interactions are made possible can vary greatly. We investigated the preferred modality of contact and students’ reasons for contact across several modalities in a first‐year biology course. We tracked student–instructor contact for two‐course instructors who team teach collaboratively  across two‐course sections. Both instructors had identical scores on student evaluations of approachability. Student–instructor contact was facilitated using five ‘student hour’ modalities: (a) in office by appointment, (b) 1 h per week, in office drop in, (c) 1 h per week, virtual chat, (d) by email, (e) 10 min immediately after class. Though email was the preferred method of contact, the period immediately following the class instruction was the most popular of the face‐to‐face options. We note significant differences in the distribution of workload across the two instructors and make recommendations for increasing the accessibility of student–instructor contact and for equity in workload to support student learning. We conducted a study to determine which of the available means of student‐instructor contact were most preferred by students. Email was the most popular means of contact, followed by in‐person contact immediately after class. We observed that the number of student contact events differed among the three members of the teaching team. Recommendations are provided for student‐centered approaches to teaching in higher education. LMSlearning management systemInteracting with instructors is an integral component of a student’s experiences in post‐secondary education. Student–instructor interactions are consistently linked with positive outcomes, including academic success , retentiHowever, the frequency of student–instructor interactions alone is not enough to ensure positive student outcomes , 13, as Despite the robust evidence for the value of high‐quality student–instructor interactions, many studies have found that these interactions are infrequent outside of class time , 20, 21.Lack of convenience and instructor unapproachability are cited as major factors limiting student engagement with office hours , 23, 24 Frequent and high‐quality, student–instructor interactions are one of the most empirically supported educational best practices in higher education  and haveStudent avoidance of office hours in their various formats supports the notion that there is a mismatch between their intended and perceived purpose. While office hours are designed to provide an opportunity for interactions which are meaningful and supportive of student success, students are either unsure of the purpose of office hours, or view office hours as opportunities for students in crisis to contact the instructor . StudentThe quality of student interactions with instructors is an important mediating factor for effecting positive student outcomes , 15, 17.Pascarella & Terenzini 1991) outlined the importance of both the frequency and the nature of interactions, theorizing that substantive topics such as research or career development posed greater benefits for students. Many of the existing scales of student–instructor interactions align with this typology, categorizing interactions based on their substantive focus 91 outlin, 16, 25.It is well established that students in higher education have preferences for certain instructors based on a number of visible and non‐visible factors , 27, 28.Which format of contact with instructors supports the highest frequency of higher‐quality (as indicated by topic of inquiry) student–instructor interaction?How might the personal qualities of the instructor impact the frequency and topic of student–instructor interactions?Our study aims to identify best practices for implementing office hours which promote frequent, high‐quality interactions between instructors and students. We compare the frequency and general topics of student–instructor interaction across several commonly used formats. We also examine how instructor gender/sex presentation predicts student interactions, which has implications for both the value of a diverse teaching team and the relative workload related to student contact for each instructor. We aim to address two research questions:Frequency and topic of student–instructor contact were tracked across five formats  for two instructors and one course coordinator in two sections of a co‐taught, first‐year biology class.The teaching team from whom data were collected are also authors on this article and so written consent was not required. Because we predicted that student knowledge of the study might reduce their learning experience in the course, and because the detail level of information collected from students in the course did not require us to seek informed consent, we obtained ethical clearances for research involving human subjects without informed consent from the University of Guelph Research Ethics Board (REB# 19‐05‐022).We collected data from the teaching team of a first‐year, introductory biology course at the University of Guelph, Ontario , during the January–April 2020 (W20) semester. ‘Discovering Biodiversity’ (BIOL 1070) is a large, introductory class which focuses on evolution, ecology, and physiology and is taken by most students within the College of Biological Science during their degree. In W20, BIOL 1070 was delivered as two‐course sections, accommodating 445 students in section 01 and 440 students in section 02. Each section enrolled different students from similar programs , who were taught the same content by the same instructors. The sections themselves are the result of classroom maximum capacity rather than differences in student cohorts or course content. Students were able to choose which section they preferred based upon their personal schedules. The sections are taught ‘back to back’ and repeated near identically by the same instructors. The teaching team includes a course coordinator (LR) to manage small‐group seminars and course logistics, and a pair of instructors who co‐teach each of the two sections together (SJ and MAS). Both instructors were involved in the delivery of the course content and taught in a conversational style with frequent and improvised transitions between themselves throughout each lecture section. The course coordinator managed all the seminar tutorials, the teaching assistant team, and all incoming emails to the course‐designated email address. All students are asked to address all inquiries to the course‐designated email address to ensure a consistent and speedy reply.Both instructors are associate professors within the Department of Integrative Biology Table . One insAt the beginning of the semester, two separate syllabi were distributed, one to each course section, indicating instructor availability for ‘student hours’. Office hours were renamed student hours with the intention of promoting more engagement with students. The syllabi indicated that one instructor would be available 1‐h per week for open, face‐to‐face student hours, while the other instructor would be available by appointment only. The mode of contact for each instructor was reversed between the two sections. The syllabi also informed students that both instructors would be available, separately at different hours for 1‐h per week for virtual student hours, where students could contact them via a ‘chat’ option on the course’s online Learning Management System (LMS). Finally, students were advised that they could contact the teaching team by emailing a course‐designated email address that was monitored by the course coordinator.Throughout the semester, as students interacted with the teaching team, we collected data on the date of the interaction, the mode of contact , the primary topic of the interaction (selected from a list of predetermined options), the student’s course section, and if it was the student’s first interaction with the instructor. Topic of the interaction included mentorship , accommodation , favors , content learning  and logistical (inquiries for information about scheduling). For the open, appointment and virtual interactions, the instructors (SJ and MAS) documented each interaction as it occurred. We also collected data from all emails directed to the course‐designated email address. Any emails directed to either instructor pertaining to the course were also forwarded to the course‐designated email address and included in our data collection. Email chains, consisting of an email and one or more responses back and forth on a single issue, were considered a single interaction. Emails where the only purpose was to book an appointment with the instructor were excluded from the data collection. From each email interaction, we then documented which of the teaching team  were addressed in the email in addition to extracting data on the previously mentioned variables.After each class, students typically have 5–10 min to engage with the instructors as they are packing up. In order to capture these interactions, two authors (BEB and VR) attended the end of each class and counted the number of students who approached each of the instructors in the first 5 min after the conclusion of classes each week. The instructors (SJ and MAS) made sure to stand at opposite ends of a large front lectern to ensure that students had to make a choice between the two of them. However, given the number of students and brevity of the interactions occurring after classes, it was not possible to collect any data on the topic of the interaction or the students’ previous interactions with the instructors.The W20 semester was affected by the global COVID‐19 pandemic. Though many of the ongoing courses ended on March 13, 2020, Discovering Biodiversity shifted to synchronous remote classes and take‐home assessments. Data collection for this study ceased on March 13, 2020, 10 weeks into a 12‐week semester to remove the impact that COVID‐19 would have on our findings.n = 326 students) made contact with at least one instructor at least once during the semester. This is consistent with previous reports indicating that approximately two‐thirds of students never use office hours [Of the total class size of 885 students between both course sections, 36.8% . While the student hour interactions represented the smallest proportion of student–instructor interactions in our study, the topics discussed tended to be the most diverse. Furthermore, the range of topics discussed was different between the three modes. While content learning was the most common topic of discussion across all three modes, this trend was most pronounced in the by‐appointment interactions, where content learning accounted for 79% of these interactions as compared to 53% during open student hours. Comparatively, mentoring occurred most frequently in open student hours (26% as compared to 3% in appointments). While both the appointment and open modes of student hours included some logistical topics, organizational interactions during appointments primarily focused on clarifying assessment expectations and arranging accommodations, whereas organizational topics regarding logistics were the focus in the open student hour sessions. Taken together these results indicate value to both the appointment and open styles of student hours. Students may interpret open student hours as a more casual format for brief questions or genuine conversation, whereas booked appointments may be interpreted as more serious, solution‐oriented sessions. Future research should explore these differences through interviews or other rich qualitative methods.The remaining 6.5% of interactions were conducted through one of the three ‘student hour’ styles . However, over the course of the semester, 25.0% of emails were addressed solely to the instructor 1 (n = 150), while only 3.2% of emails were addressed solely to instructor 2 (n = 19), which was a significant increase from a 50 : 50 ratio  and were most often sent to their personal addresses despite instructions to use the course‐designated email address. An additional 2.8% of emails were addressed to both of the instructors (n = 17). The final 69.1% of the emails (n = 415) were either unaddressed, addressed to the course coordinator, or addressed to a combination of teaching staff that included at least one instructor and the course coordinator. The topics discussed with each of the instructors also differed substantially  These other activities might include the writing of exams or assignments, preparation of teaching materials, or grading.If instructors are not team teaching: recognize that some instructors  are more likely to have more individual contact time with students by increasing the weight that each course has, especially large courses, on their workload distribution.The burden should not be on instructors, especially those most likely to be contacted by students, to offer a lesser educational service to students due to disparities in actual contact time among instructors in teaching teams. Doing so places the responsibility upon instructors to choose between an increase in workload or offering a lesser teaching experience that could harm their career progression. Administrators need to build within their systems the recognition that instructor differences in workload exist and that student–instructor contact outside of class are valuable educational opportunities. As such, support should be provided to instructors from equity‐seeking communities in a tangible way. Examples include:The authors declare no conflict of interest.All authors participated in the data collection as described in the methods and all authors participated in the design. BEB and VR analyzed the data and wrote the first draft and SJ, LR, and MAS provided revisions. SJ conceived of the study.


According to the present case, urine BCG PCR might be an option for patients (i) who need to undergo an invasive procedure and (ii) who had persistent aseptic pyuria. Although urine BCG PCR test is not included in clinical practice, it might be helpful to recognize the risk of severe systemic tuberculosis after BCG therapy.The association between BCG persistence and antitumor response is not known. BCG persistence in the bladder for a long time may cause late‐onset BCG infection but that may cause a long‐term durable response. Further study is necessary to address the long‐term persistence of BCG may be beneficial or harmful for the patient with high‐risk non‐muscle‐invasive bladder.The authors declare no conflict of interest.


The development of the human immune system during embryonic and fetal life has historically been difficult to research due to limited access to human tissue. Experimental animal models have been widely used to study development but cellular and molecular programmes may not be conserved across species. The advent of multiomic single‐cell technologies and an increase in human developmental tissue biobank resources have facilitated single‐cell multiomic studies focused on human immune development. A critical question in the near future is "How do we best reconcile scientific findings across multiple omic modalities, developmental time, and organismic space?" In this review, we discuss the application of single‐cell multiomic technologies to unravel the major cellular lineages in the prenatal human immune system. We also identify key areas where the combined power of multiomics technologies can be leveraged to address specific immunological gaps in our current knowledge and explore new research horizons in human development. BioRender.com.Recent advances in developmental immunology have been driven by improvements in single cell multi omic technologies, integrative bioinformatic analysis tools, and global consortia efforts. Herein, we detail these advances, which pave way for a deeper understanding of prenatal immunity and the genetic perturbations that drive disease during prenatal development. Illustration created with  Single‐cell technologies are often regarded as recently developed approaches for studying cellular biology, however, we have had the ability to evaluate individual cells for centuries. During the 1800s, and with the help of the invention of the microscope, scientists described the expansion of leukocytes in disease [Multiomics refers to cellular characterization through multiple omics levels including genome (DNA), transcriptome (RNA), proteome (protein), and epigenome . Genomics was the first omics discipline to be deployed at scale to interrogate genomic polymorphisms , protein+ DCs was shown to consist of two further populations and two additional monocyte fractions were also detected. Additionally, the presence of a proliferating DC progenitor within peripheral blood was identified [Transcriptomics, the genome‐wide analysis of RNA , has revealed that a large proportion of the genome is noncoding , and thaentified . It mustStudying the epigenome of single cells can inform how modifications to DNA or DNA‐associated proteins facilitate cellular interactions and lineage specification . Single‐The field of single‐cell proteomics has historically lagged slightly behind the genomics field, due to a limit on the quantity of proteins that can be measured at any one time at sufficient sensitivity. Many of these proteomic methods rely on tagged antibodies which have been effectively used in recent studies. For example, flow cytometry can be combined with single‐cell mRNA data for protein‐level validation. Furthermore, cytometry by time of flight (CyTOF) uses heavy metal ions conjugated to antibodies, and has been used to measure the proteins of individual cord blood cells to reveal cell‐fate decisions during erythropoiesis and track changes in transcription factor expression during lineage commitment . An emerStudies using only one omic level of information may lack nuance, for example, a purely transcriptomic study may miss the importance of RNA/DNA/protein regulation to cell function. Multiomic technologies can be combined to fully understand cellular function Fig. . They caNewer techniques, such as Cellular Indexing of Transcriptomes and Epitopes by Sequencing (CITE‐seq) , BD RhapAlthough a combination of transcriptome and proteome approaches has been most popular in efforts toward multiomic experimental design, combinations of different omic technologies are also valuable. Combined genome and transcriptome analysis  , 33. SimHuman developmental research has far‐reaching impacts including innovations in tissue engineering and understanding postnatal disease. The re‐emergence of developmental signaling pathways in adult life has been shown to be a result of genetic mutations or epigenetic reconstruction that may lead to cancer . The bioThe primary development of the blood and immune systems in vertebrates occurs in two waves; the primitive wave and the definitive wave  Fig. 2)2). The pAt 3‐4 PCW, the first intraembryonic progenitors are formed in the aorta‐gonad‐mesonephros (AGM); a region of the embryonic mesoderm that transiently gives rise to blood and immune cells . YS and It is not yet established how hematopoietic stem cell (HSC) expansion and differentiation is supported in the FL but interestingly, the HSC pool expands rapidly in the FL, compared to the BM where HSCs are mostly quiescent . Mouse sThe fetal BM is then colonized by blood and immune progenitors at around 11 PCW and becomes the dominant site of hematopoiesis after 20 PCW and into adulthood . All bloA study by Notta et al. profiled 3000 stem and progenitor cells using a variety of single‐cell methods including scRNA‐seq, single‐ cell in‐vitro culture, and flow cytometry . They prIt is also important to note the value of reanalyzing the increasing numbers of transcriptome datasets  for further biological insights. Granulocyte‐monocyte precursors (GMPs) from published murine single‐cell transcriptomic datasets , 48 haveThe mononuclear phagocyte system (MPS) is composed of monocytes, macrophages, and DCs that link the innate and adaptive immune systems. Murine fate mapping and in‐vitro studies have been the basis of our knowledge of the lineages of the MPS. These studies have also revealed important differences of these lineages in early development and the adult equivalent .Our understanding of human fetal monocyte functionality is currently limited. Using single‐cell transcriptomics, we have recently shown that they do correlate with classical adult monocytes . AdditioIn adult life, DCs are involved in the initiation and regulation of adaptive immune responses and are essential for establishing immunological memory. However, during prenatal development DCs have a role in building tolerance . The DC Macrophages in adults can originate either from prenatal YS‐derived progenitors or BM HSC/progenitors via a monocyte intermediate state. This is reflected in their diverse range of functions including regulating homeostasis, chaperoning the maturation of fetal tissues, and their well‐known roles in immunity . As mentBian et al. used scRNA‐seq to study the ontogeny of YS‐derived macrophages in detail and identified two HSC‐independent pathways of macrophage development . They prVCAM1 in liver and F13A1 in skin, compared to other cells of the MPS [Additionally, fetal macrophages express specific tissue markers, such as  the MPS , another the MPS .PLZF and TCF1 [Innate lymphoid cells (ILCs), including NK cells, are heterogeneous and plastic in steady state as well as in disease. Their characterization has been aided by single‐cell sequencing studies . During and TCF1 . Analyseand TCF1 . Single‐and TCF1 .Additionally, Baerenwaldt et al. illustrated the role of Flt3L and IL‐7 in the development of ILCs in mice. Flt3L appeared to be essential for early differentiation of ILCs from progenitors cultured from the FL, whereas IL‐7 was more important for the development of ILCs in peripheral organs such as the spleen . It woulThe distinction between antibody‐producing lymphocytes and thymus‐derived lymphocytes was first proposed in 1965, through convergent experimentation in birds and mammals , 68. SinThe molecular regulation of B‐lineage commitment  has been investigated in adult mice at the single‐cell resolution using FACs, microarray, and single‐cell culturing , 74, andDouble positive, proliferating, mature, and recombining thymocytes cells have been identified in adult mice using single‐cell transcriptomics , in a stIn the context of human life, T‐cell heterogeneity in lungs, lymph nodes, BM, and blood have been profiled in both health and disease using scRNA‐seq . In the It would now be timely to generate multiomic maps of organs implicated in B‐cell and T‐cell differentiation , in order to further understand the adaptive immune response and its formation during healthy human development. We could answer specific questions such as which B or T cell states are present throughout fetal organs over gestation and what, if any, functionality they have. It would also be advantageous to know from a clinical perspective how lymphoid receptor (BCR/TCR) clonal expansion is patterned across fetal organs during human development, and if detected, what utility clonality offers prior to antigen challenge.Recognizing the genetic basis of diseases implicated in dysregulation of B or T lymphopoiesis could have an impact on clinical therapy. For example, in B‐cell acute lymphoblastic leukemia, which is thought to have origins during early development. Transcriptomic studies could be built upon to further develop in‐vitro organoid culture models of human in‐vivo thymic tissue. Transcriptomic data could also be reanalyzed with additional chromatin and/or proteome data to help further understand the role of thymus in acquired and congenital T‐cell deficiency syndromes such as Wiskott–Aldrich syndrome.Approaches for multiomic data integration  are constantly improving, and it is now becoming conceivable that, with added scalability, we could create cellular atlases of organs with a multiomic level of detail. Beyond this point, fundamental questions will remain, for example: (1) How well do multiomic profiles of isolated cells match up to those in an in‐vivo environment? (2) How does stochasticity of gene expression and protein influx/efflux affect (or otherwise bias) our understanding of cellular function? (3) How can we best create a data visualization platform that is both intuitive to scientists and nonscientists, and able to represent data at multiple omics levels simultaneously ?Distilling the intricacies of immunopoiesis during human development cannot be done with multiomic approaches alone; a concert of complementary techniques must also be incorporated into experimental plans. By design, omic studies rely upon sampling of accessible material, a resource which is not available at the earliest stages of human development such as the preimplantation stage. This limitation can be overcome through use of in‐vitro models, which, alongside organoid and animal models, have the added benefit of being amenable to genetic and molecular perturbation. These complementary techniques facilitate mechanistic studies and lineage mapping, and allow for development to be studied in real time as opposed to the "snapshot" time‐series nature that many multiomic experiments have.www.hdbr.org), the largest fetal tissue bank in the UK.Human developmental research has benefited from a recent surge in resolution, facilitated by previously described technological advancements in single‐cell omics, combined with improved access to human embryonic and fetal material. Access to research material has greatly improved thanks to tissue repositories supporting human development research, such as the Human Developmental Biology Resource (HDBR: International ventures, such as HDBR and its equivalents, allow researchers to expand beyond animal models and in‐vitro culture models. Although these are valuable particularly for early developmental stages, when samples are inaccessible and are amenable to perturbation and genetic manipulation, there are species‐specific differences which must be resolved . The intThe HDCA aims to "generate a comprehensive profile of all cell types and states present during development" using molecular and spatial methods to provide a 3D atlas. The HDCA has already published atlas type works on organs implicated in immunopoiesis, such as YS and FL  and fetaMultiomics has shown great potential in the analyses of developing human tissues. We are now in an era where we can survey multiple molecules from individual cells on an enormous scale, providing a level of detail previously unimaginable. These new omics studies have identified new cell types within lineages and revealed new roles for known cells. Large scale and high throughput profiling of cells, tissues, and organ systems will discover emergent properties that we would not have exposed by looking at individual lineages. To uncover the ontogeny of the immune system in great detail will allow us to demonstrate how genetic perturbations drive disease, especially those with origins during prenatal development. Global consortia efforts will be crucial to successfully deliver such analyses at this scale.The authors declare no financial or commercial conflict of interest.AGMaorta‐gonad mesonephrosCITE‐seqcellular indexing of transcriptomes and epitopes by sequencingFLfetal liverGMPgranulocyte‐monocyte precursorsHDBRhuman developmental biology resourceHDCAhuman development cell atlasHSChematopoietic stem cellsILCsinnate lymphoid cellsLTilymphoid tissue inducerMPSmononuclear phagocyte systemPCWpostconception weekspDCplasmacytoid DCsREAP‐seqRNA expression and protein sequencing assayscATAC‐seqsingle‐cell assay for transposable‐accessible chromatin w/sequencingsci‐ATAC‐seqsingle‐cell combinatorial indexing ATAC‐seqscNMT‐seqsingle‐cell nucleosome, methylation and transcription sequencingSCoPE‐MSsingle‐cell proteomics by mass spectrometryscRRBSsingle‐cell reduced representation bisulfite sequencingYSyolk sac


The impact of Adverse Childhood Experiences (ACEs) on the physical and mental well–being of older adults with Opioid Use Disorder (OUD) is unclear, and we know even less about gender differences. This study explores this association and investigates additional factors  that may affect physical and mental well–being in this population with a focus on gender. The sample for the present analysis includes 90 adults aged 50 and older from a larger study focused on aging with OUD across eight opioid treatment programs in Georgia. We performed multivariable linear regression analyses by gender. There was a small, but significant, association between ACEs and mental well–being for men only. Other significant predictors of physical and mental well-being  varied by gender. We discuss the importance of these gender differences in identifying appropriate areas for intervention to improve physical and mental well–being.