Age and Gender Differences in Social Network Composition and Social Support Among Older Rural South Africans: Findings From the HAALSI Study

OBJECTIVES: Drawing on the “Health and Aging in Africa: A Longitudinal Study of an INDEPTH community in South Africa” (HAALSI) baseline survey, we present data on older adults’ social networks and receipt of social support in rural South Africa. We examine how age and gender differences in social network characteristics matched with patterns predicted by theories of choice- and constraint-based network contraction in older adults. METHOD: We used regression analysis on data for 5,059 South African adults aged 40 and older. RESULTS: Older respondents reported fewer important social contacts and less frequent communication than their middle-aged peers, largely due to fewer nonkin connections. Network size difference between older and younger respondents was greater for women than for men. These gender and age differences were explicable by much higher levels of widowhood among older women compared to younger women and older men. There was no evidence for employment-related network contraction or selective retention of emotionally supportive ties. DISCUSSION: Marriage-related structural constraints impacted on older women’s social networks in rural South Africa, but did not explain choice-based network contraction. These findings suggest that many older women in rural Africa, a growing population, may have an unmet need for social support

A silicon-labelled amino acid suitable for late-stage fluorination and unexpected oxidative cleavage reactions in the preparation of a key intermediate in the Strecker synthesis

A novel silicon-substituted phenylalanine derivative was prepared using the Strecker amino acid synthesis. An unexpected oxidative cleavage was observed in the preparation of the aldehyde required for the Strecker reaction. In this step, a homobenzylic alcohol intermediate was oxidatively cleaved to the corresponding benzaldehyde using either chromium or palladium based oxidants. This undesired side reaction was overcome through the use of Dess-Martin Periodinane, or through an efficient TEMPO-bleach oxidation. The amino acid prepared in this study was then labelled with fluoride in aqueous solvent using a range of fluoride sources. The efficiency of this labelling motivates future studies in late-stage fluorination of peptide and protein therapeutics for use in positron emission tomography

Norbornene Probes for the Detection of Cysteine Sulfenic Acid in Cells.

Norbornene derivatives were validated as probes for cysteine sulfenic acid on proteins and in live cells. Trapping sulfenic acids with norbornene probes is highly selective and revealed a different reactivity profile than the traditional dimedone reagent. The norbornene probe also revealed a superior chemoselectivity when compared to a commonly used dimedone probe. Together, these results advance the study of cysteine oxidation in biological systems

Endo180 (MRC2) antibody-drug conjugate for the treatment of sarcoma.

Although the 5-year survival rates for sarcoma patients have improved, the proportion of patients relapsing after first line treatment remains high and survival of patients with metastatic disease is dismal. Moreover, the extensive molecular heterogeneity of the multiple different sarcoma subtypes poses a substantial challenge to developing more personalized treatment strategies. From immunohistochemical staining of a large set of 625 human soft tissue sarcomas we demonstrate strong tumor cell staining of the Endo180 (MRC2) receptor in a high proportion of samples, findings echoed in gene expression datasets showing a significantly increased expression in both soft tissue and bone sarcomas compared to normal tissue. Endo180 is a constitutively recycling transmembrane receptor and therefore an ideal target for an antibody-drug conjugate (ADC). An anti-Endo180 monoclonal antibody conjugated to the anti-mitotic agent, MMAE via a cleavable linker, is rapidly internalized into target cells and trafficked to the lysosome for degradation, causing cell death specifically in Endo180 expressing sarcoma cell lines. In a sarcoma tumor xenograft model, the Endo180-vc-MMAE ADC, but not an Isotype-vc-MMAE control or the unconjugated Endo180 antibody, drives on target cytotoxicity resulting in tumor regression and a significant impairment of metastatic colonization of the lungs, liver and lymph nodes. These data, together with the lack of a phenotype in mice with an Mrc2 genetic deletion, provide pre-clinical proof-of-principle evidence for the future development of an Endo180-ADC as a therapeutic strategy in a broad range of sarcoma subtypes and, importantly, with potential impact both on the primary tumor and in metastatic disease

Identification of major hemorrhage in trauma patients in the prehospital setting: diagnostic accuracy and impact on outcome.

BACKGROUND: Hemorrhage is the most common cause of potentially preventable death after injury. Early identification of patients with major hemorrhage (MH) is important as treatments are time-critical. However, diagnosis can be difficult, even for expert clinicians. This study aimed to determine how accurate clinicians are at identifying patients with MH in the prehospital setting. A second aim was to analyze factors associated with missed and overdiagnosis of MH, and the impact on mortality. METHODS: Retrospective evaluation of consecutive adult (≥16 years) patients injured in 2019-2020, assessed by expert trauma clinicians in a mature prehospital trauma system, and admitted to a major trauma center (MTC). Clinicians decided to activate the major hemorrhage protocol (MHPA) or not. This decision was compared with whether patients had MH in hospital, defined as the critical admission threshold (CAT+): administration of ≥3 U of red blood cells during any 60-minute period within 24 hours of injury. Multivariate logistical regression analyses were used to analyze factors associated with diagnostic accuracy and mortality. RESULTS: Of the 947 patients included in this study, 138 (14.6%) had MH. MH was correctly diagnosed in 97 of 138 patients (sensitivity 70%) and correctly excluded in 764 of 809 patients (specificity 94%). Factors associated with missed diagnosis were penetrating mechanism (OR 2.4, 95% CI 1.2 to 4.7) and major abdominal injury (OR 4.0; 95% CI 1.7 to 8.7). Factors associated with overdiagnosis were hypotension (OR 0.99; 95% CI 0.98 to 0.99), polytrauma (OR 1.3, 95% CI 1.1 to 1.6), and diagnostic uncertainty (OR 3.7, 95% CI 1.8 to 7.3). When MH was missed in the prehospital setting, the risk of mortality increased threefold, despite being admitted to an MTC. CONCLUSION: Clinical assessment has only a moderate ability to identify MH in the prehospital setting. A missed diagnosis of MH increased the odds of mortality threefold. Understanding the limitations of clinical assessment and developing solutions to aid identification of MH are warranted. LEVEL OF EVIDENCE: Level III-Retrospective study with up to two negative criteria. STUDY TYPE: Original research; diagnostic accuracy study

Interviewer-driven Variability in Social Network Reporting: Results from Health and Aging in Africa: a Longitudinal Study of an INDEPTH community (HAALSI) in South Africa

Social network analysis depends on how social ties to others are elicited during interviews, a process easily affected by respondent and interviewer behaviors. We investigate how the number of self-reported important social contacts varied within a single data collection round. Our data come from Health and Aging in Africa: a Longitudinal Study of an INDEPTH community (HAALSI), a comprehensive population-based survey of individuals aged 40 years and older conducted over 13 months at the Agincourt health and demographic surveillance site in rural South Africa. As part of HAALSI, interviewers elicited detailed egocentric network data. The average number of contacts reported by the 5,059 respondents both varied significantly across interviewers and fell over time as the data collection progressed, even after adjusting for respondent, interviewer, and respondent–interviewer dyad characteristics. Contact numbers rose substantially after a targeted interviewer intervention. We conclude that checking (and adjusting) for interviewer effects, even within one data collection round, is critical to valid and reliable social network analysis. Measurements of social networks depend on the number and type of social ties to others (Berkman et al. 2000; Smith and Christakis 2008). These ties are typically elicited through interviews, a process easily affected by respondent or interviewer characteristics and behaviors. Understanding social network structure and composition requires substantial amounts of information from respondents (“egos”) about the people (“alters”) they have relationships with (Marsden 1990). Notably, the survey burden associated with network data collection depends heavily on the number of alters elicited through “name generator” questions: Each alter named leads to the repetition of all follow-up questions characterizing the ego–alter relationship (“name interpreters”; Burt 1984). Interviewers have been identified as a key source of variation in survey responses, particularly for questions that are attitudinal, ambiguous, or have complex skip patterns (West and Blom 2016). Several studies have previously identified interviewer effects on network size (Brüderl et al. 2013; Josten and Trappmann 2016; Marsden 2003; Paik and Sanchagrin 2013; van Tilburg 1998). These interviewer effects may arise from differential understanding of survey questions, and therefore how questions are presented to respondents. Interviewers can also affect which alters are elicited due to their own characteristics (e.g., sex, race, age, or experience), or the nature of the interviewer–respondent dyad (e.g., gender, race, or age homophily), leading to different lines of enquiry, levels of probing, or expectations of social acceptability (Collins 1980; Hox 1994; Marsden 2003; Phung et al. 2015). Furthermore, if respondents or interviewers are aware that naming more alters substantially increases survey length, then either group may consciously or unconsciously seek to minimize the number of alters named (Eagle and Proeschold-Bell 2015; van der Zouwen and van Tilburg 2001). In cross-sectional surveys, the opportunities for respondents to learn are limited, but those for interviewers will increase as the survey period progresses. Interviewers may try to reduce survey burden, either for themselves or for respondents, by favoring language or probes that decrease the number of alters elicited. Indeed, past studies in Europe have found evidence of interviewers intentionally filtering out questions by entering fewer responses that would trigger more questions. Such filtering behavior has been seen in Europe for interviewers who are being compensated by the interview rather than by the hour (Josten and Trappmann 2016; Kosyakova et al. 2014), for interviewers with prior experience using the relevant screening tool (Matschinger et al. 2005), and where interviewers are under substantial pressure to complete more interviews (Schnell and Kreuter 2000). We aim to extend this literature by assessing how the number of alters elicited systematically changed over the course of a cross-sectional social network survey of older adults in rural South Africa. We show a substantial drop in alter numbers over time, and a swift reversal following retraining, providing substantial evidence for interviewer effects

Chemical speciation of nanoparticles surrounding metal-on-metal hips.

Spectromicroscopy of tissue surrounding failed CoCr metal-on-metal hip replacements detected corroded nanoscale debris in periprosthetic tissue in two chemical states, with concomitant mitochondrial damage. The majority of debris contained Cr(3+), with trace amounts of oxidised cobalt. A minority phase containing a core of metallic chromium and cobalt was also observed