Gwynedd Council

Background: Transmembrane-4-L-six-family member-1 (TM4SF1) is a tetraspanin superfamily member that is overexpressed in cancers such as breast, colon, lung, liver, and prostate. A contributor to tumor development and progression, TM4SF1 participates in microdomains that regulate cancer cell migration and invasion via induction of the epithelial-mesenchymal transition, and angiogenesis. The overexpression of TM4SF1 makes it an attractive target for the developing novel treatments of GI tract cancers. Methods and Results: We have engineered an anti-TM4SF1 antibody that binds with nM affinity to TM4SF1-expressing cells. The mAb has anti-tumor growth inhibition in gastric, ovarian cancer cell lines. This mAb can serve as an efficacious targeting carrier for toxins in an ADC and for siRNA in an ARC. To broaden the scope of cancer cell engagement, we prepared constructed a TM4SF1-cMET bispecific ADC which showed potent cytotoxicity in multiple GI, lung, ovarian, breast, TNBC, and pancreatic cancer cell lines in in vitro cell cytotoxicity assays. The bispecific TM4SF1-cMET MMAE (DAR=4) treatment led to potent tumor growth inhibition (70% to 95% TGI) in CDX pancreatic and gastric cancer xenograft models. The mice in the TM4SF1-cMET MMAE treatment group maintained normal body weight throughout the treatment course without observed toxicity. The TM4SF1 - MYC siRNA conjugates were stable. Treatment of MYC-dependent cancer lines led to MYC protein knockdown and cell growth inhibition. Conclusions: A bispecific TM4SF1 ADC had activity in multiple cancer cell lines. Notably, the TM4SF1-MMAE molecule showed potent in vivo tumor growth inhibition in ovarian, pancreatic, and gastric cell lines. The TM4SF1 - siRNA ARC had tumor cell proliferation inhibition in lung, pancreatic, and gastric cancer cell lines. Preclinical safety assessment, pharmacokinetics and IND-enabling studies are on-going with the goal of developing TM4SF1 as the “best-in-class” ADC molecule for the treatment of lung, gastric, breast, and pancreatic cancers with significant unmet medical needs. This antibody can be applied to alternative targeting modalities. Citation Format: Mingquan Xie, Peter Li, Han Lu, ShuTing Dong, Nicole Wilski, Poonam Pandey, Nishida Motohiko, Peter Haytko, Mark Chiu, Maria P. MacWilliams. TM4SF1 as a novel target for different modalities (mAb, bispecific ADC, targeted siRNA) for the treatment of different solid tumor cancers [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2025; Part 1 (Regular Abstracts); 2025 Apr 25-30; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2025;85(8_Suppl_1):Abstract nr 2880.

To compare the prognostic value of mid-upper arm circumference (MUAC), weight-for-height Z-score (WHZ) and weight-for-age Z-score (WAZ) for predicting death over periods of 1, 3 and 6 months follow-up in children. Pooled analysis of twelve prospective studies examining survival after anthropometric assessment. Sensitivity and false-positive ratios to predict death within 1, 3 and 6 months were compared for three individual anthropometric indices and their combinations. Community-based, prospective studies from twelve countries in Africa and Asia. Children aged 6-59 months living in the study areas. For all anthropometric indices, the receiver operating characteristic curves were higher for shorter than for longer durations of follow-up. Sensitivity was higher for death with 1-month follow-up compared with 6 months by 49 % (95 % CI (30, 69)) for MUAC < 115 mm (P < 0·001), 48 % (95 % CI (9·4, 87)) for WHZ < -3 (P < 0·01) and 28 % (95 % CI (7·6, 42)) for WAZ < -3 (P < 0·005). This was accompanied by an increase in false positives of only 3 % or less. For all durations of follow-up, WAZ < -3 identified more children who died and were not identified by WHZ < -3 or by MUAC < 115 mm, 120 mm or 125 mm, but the use of WAZ < -3 led to an increased false-positive ratio up to 16·4 % (95 % CI (12·0, 20·9)) compared with 3·5 % (95 % CI (0·4, 6·5)) for MUAC < 115 mm alone. Frequent anthropometric measurements significantly improve the identification of malnourished children with a high risk of death without markedly increasing false positives. Combining two indices increases sensitivity but also increases false positives among children meeting case definitions.

ABSTRACTChildhood wasting and stunting affect large numbers of children globally. Both are important risk factors for illness and death yet, despite the fact that these conditions can share common risk factors and are often seen in the same child, they are commonly portrayed as relatively distinct manifestations of undernutrition. In 2014, the Wasting and Stunting project was launched by the Emergency Nutrition Network. Its aim was to better understand the complex relationship and associations between wasting and stunting and examine whether current separations that were apparent in approaches to policy, financing, and programs were justified or useful. Based on the project's work, this article aims to bring a wasting and stunting lens to how research is designed and financed in order for the nutrition community to better understand, prevent, and treat child undernutrition. Discussion of lessons learnt focuses on the synergy and temporal relationships between children's weight loss and linear growth faltering, the proximal and distal factors that drive diverse forms of undernutrition, and identifying and targeting people most at risk. Supporting progress in all these areas requires research collaborations across interest groups that highlight the value of research that moves beyond a focus on single forms of undernutrition, and ensures that there is equal attention given to wasting as to other forms of malnutrition, wherever it is present.

Children with weight-for-age z-score (WAZ) <-3 have a high risk of death, yet this indicator is not widely used in nutrition treatment programming. This pooled secondary data analysis of children aged 6-59 months aimed to examine the prevalence, treatment outcomes, and growth trajectories of children with WAZ <-3 versus children with WAZ ≥-3 receiving outpatient treatment for wasting and/or nutritional oedema, to inform future protocols. Binary treatment outcomes between WAZ <-3 and WAZ ≥-3 admissions were compared using logistic regression. Recovery was defined as attaining mid-upper-arm circumference ≥12.5 cm and weight-for-height z-score ≥-2, without oedema, within a period of 17 weeks of admission. Data from 24,829 children from 9 countries drawn from 13 datasets were included. 55% of wasted children had WAZ <-3. Children admitted with WAZ <-3 compared to those with WAZ ≥-3 had lower recovery rates (28.3% vs. 48.7%), higher risk of death (1.8% vs. 0.7%), and higher risk of transfer to inpatient care (6.2% vs. 3.8%). Growth trajectories showed that children with WAZ <-3 had markedly lower anthropometry at the start and end of care, however, their patterns of anthropometric gains were very similar to those with WAZ ≥-3. If moderately wasted children with WAZ <-3 were treated in therapeutic programmes alongside severely wasted children, we estimate caseloads would increase by 32%. Our findings suggest that wasted children with WAZ <-3 are an especially vulnerable group and those with moderate wasting and WAZ <-3 likely require a higher intensity of nutritional support than is currently recommended. Longer or improved treatment may be necessary, and the timeline and definition of recovery likely need review.

Mevlânâ Celâleddîn-i Rûmî (ö. 672/1273) Türk tasavvuf edebiyatına yön veren büyük bir değerdir. Telif ettiği eserlerinin etkisi, çağları aşarak günümüze ulaşmıştır. Mevlânâ ve Mevlevîliğe dair bugüne kadar birçok eser yazılmıştır. Bunlara kaynak teşkil eden eserlerden biri olan Menâkıbü’l-Ârifîn, tarikat geleneği içerisinde yetişen Ahmed Eflâkî (ö. 761/1360) tarafından Farsça kaleme alınmıştır. Eflâkî’nin bu dinî-tasavvufî eseri Sultan II. Murâd (salt. 1421-1444, 1446-1451) döneminde ilk defa Mahzenü’l-Esrâr adıyla Anadolu Türkçesine tercüme edilmiştir. Eserde Mevlevî dergâhına mensup kadınlara dair anlatılar dikkat çekicidir. Kira Hatun, Melike Hatun, Mutahhara Hatun, Şeref Hatun, Fâtıma Hatun gibi eş, çocuk, torun, gelin vb. Mevlânâ’yla birinci derecede akrabalık ilişkisi bulunan kadınların; Gömeç Hatun, Hoşlika Hatun, Gürcü Hatun, Paşa Hatun gibi Mevlânâ’nın ailesi dışından olup dergâha intisap etmiş, maddi/manevi desteği olan müridelerin, sultan hanımlarının hikâyeleri anlatılmıştır. Bu çalışmada, Mevlânâ ve dergâhı ile olan münasebetlerinden yola çıkılarak Mahzenü’l-Esrâr’da bahsi geçen kadınlar statü, yaşam biçimi, hayat duruşu vb. konularda “kadın motifi” çerçevesinde incelenecektir.

Societal Impact StatementHuman‐caused habitat destruction and transformation is resulting in a cascade of impacts to biological diversity, of which arguably the most fundamental is species extinctions. The Global Conservation Consortia (GCC) are a means to pool efforts and expertise across national boundaries and between disciplines in the attempt to prevent such losses in focal plant groups. GCC Erica coordinates an international response to extinction threats in one such group, the heaths, or heathers, of which hundreds of species are found only in South Africa's spectacularly diverse Cape Floristic Region.SummaryEffectively combating the biodiversity crisis requires coordinated conservation efforts. Botanic Gardens Conservation International (BGCI) and numerous partners have established Global Conservation Consortia (GCC) to collaboratively develop and implement comprehensive conservation strategies for priority threatened plant groups. Through these networks, institutions with specialised collections and staff can leverage ongoing work to optimise impact for threatened plant species. The genus Erica poses a challenge similar in scale to that of the largest other GCC group, Rhododendron, but almost 700 of the around 800 known species of Erica are concentrated in a single biodiversity hotspot, the Cape Floristic Region (CFR) of South Africa. Many species are known to be threatened, suffering the immediate impacts of habitat destruction, invasive species, changes in natural fire regimes and climate change. Efforts to counter these threats face general challenges: disproportionate burden of in situ conservation falling on a minority of the community, limited knowledge of species‐rich groups, shortfalls in assessing and monitoring threat, lack of resources for in situ and limitations of knowledge for ex situ conservation efforts and in communicating the value of biological diversity to a public who may never encounter it in the wild. GCC Erica brings together the world's Erica experts, conservationists and the botanical community, including botanic gardens, seed banks and organisations in Africa, Madagascar, Europe, the United States, Australia and beyond. We are collaboratively pooling our unique sets of skills and resources to address these challenges in working groups for conservation prioritisation, conservation in situ, horticulture, seed banking, systematic research and outreach.

ABSTRACT The amenity tree valuation method CAVAT apparently gives reduced weight to future benefits, similarly to discounting. Discounting future conditions allows calculation of a value per year per square centimetre of tree basal area, on the premise that tree planting was rationally done. The resulting value ascribed to a target tree is much lower than that calculated by CAVAT. CAVAT’s value is the same as given by the “rational” procedure if trees were predicted not to grow. The “rational” perspective provides a reasoned estimate of CAVAT’s avowed objective of calculating a compensation replacement value for lost trees. CAVAT itself seemingly calculates over-generous compensation. The “rational” protocol’s apparently low value may be adjusted upwards to recognise incomplete planting survival, conditions of high cost, overheads and, sometimes, defective discounting. These, and any neglect of the value of subsequent replanting and of people’s particular associations with trees, may undervalue fair financial recompense, especially when no compensation planting is made. However, some of these factors would revise CAVAT values upwards too, so the gap between outcomes might remain. Neither protocol translates from a cost basis to a full amenity benefit of trees.

Abstract BackgroundExcess male morbidity and mortality is well recognised in neonatal medicine and infant health. In contrast, within global nutrition, it is commonly assumed that girls are more at-risk of experiencing undernutrition. We aimed to explore evidence for any male/female differences in child undernutrition using anthropometric case definitions and the reasons for differences observed.MethodsWe searched: Medline, Embase, Global health, Popline and Cochrane databases with no time limits applied. Eligible studies focused on children aged 0-59 months affected by undernutrition where sex was reported. In the meta-analysis, undernutrition-specific estimates were examined separately for wasting, stunting and underweight using a random effects model.Results76 studies were identified: 46/76 studies were included in the meta-analysis. In 20 which examined wasting, boys had higher odds of being wasted than girls (pooled OR 1.26, 95% CI 1.13-1.40). 39 examined stunting: boys had higher odds of stunting than girls (pooled OR 1.31 95% CI 1.24-1.39). 25 explored underweight: boys had higher odds of being underweight than girls (pooled OR 1.19, 95% CI 1.07-1.32). There was some limited evidence that the female advantage indicating lower risk of stunting and underweight was weaker in South Asia than other parts of the world.44/76 (58%) studies discussed possible reasons for boy/girl differences; 11/76 (14%) cited studies with similar findings with no further discussion; 21/76 (28%) had no sex difference discussion. 6/44 studies (14%) postulated biological causes, 21/44 (48%) social causes and 17/44 (38%) to a combination.ConclusionOur review indicates that undernutrition in children under 5 is more likely to affect boys than girls, though the magnitude of these differences varies and is more pronounced in some contexts than others. Future research should further explore reasons for these differences and implications for nutrition policy and practice.Key QuestionsWhat is already known?Undernutrition (wasting, stunting, and underweight) is a public health problem affecting millions of children aged under 5 years globally.Although higher neonatal and infant morbidity/mortality for boys is well described, little attention has been given to sex differences in the field of undernutrition due to an assumption that girls are very often disadvantaged over boys.What are the new findings?In most settings studied, undernutrition is more common among boys than girls, though the extent of these differences varies and is reversed in a few contexts.Both biological and social mechanisms have been proposed to be responsible for the observed differences as well as a combination of the two.What do the new findings imply?Greater awareness of actual sex differences is needed within the field of nutrition. While sex-specific data is routinely analysed and reported in nutrition surveys it should be used in nutrition programming to better identify and understand what differences exist. Analysis should assess if the sex balance in programme admissions is reflective of the population undernutrition burden.Further research is needed to understand the mechanisms that lead to sex and gender differences in undernutrition and their implications. Better epidemiological understanding is a priority, as is work to explore their consequent effects on morbidity and mortality.

The Photogrammetric RecordVolume 33, Issue 164 p. 396-405 Editorial First World War aerial photography: 1918 Stuart I. Granshaw, Harlech, Gwynedd, WalesSearch for more papers by this author Stuart I. Granshaw, Harlech, Gwynedd, WalesSearch for more papers by this author First published: 10 January 2019 https://doi.org/10.1111/phor.12260Citations: 2Read the full textAboutPDF ToolsRequest permissionExport citationAdd to favoritesTrack citation ShareShare Give accessShare full text accessShare full-text accessPlease review our Terms and Conditions of Use and check box below to share full-text version of article.I have read and accept the Wiley Online Library Terms and Conditions of UseShareable LinkUse the link below to share a full-text version of this article with your friends and colleagues. Learn more.Copy URL Share a linkShare onEmailFacebookTwitterLinked InRedditWechat Citing Literature Volume33, Issue164December 2018Pages 396-405 RelatedInformation