Immunogenicity and safety of a fourth homologous dose of NVX-CoV2373.

The emergence of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variants has significantly reduced the efficacy of some approved vaccines. A fourth dose of NVX-CoV2373 (5 µg SARS-CoV-2 recombinant spike [rS] protein + 50 µg Matrix-M™ adjuvant; Novavax, Gaithersburg, MD) was evaluated to determine induction of cross-reactive antibodies to variants of concern. A phase II randomized study (NCT04368988) recruited participants in Australia and the United States to assess a primary series of NVX-CoV2373 followed by two booster doses (third and fourth doses at 6-month intervals) in adults 18-84 years of age. The primary series was administered when the SARS-CoV-2 ancestral strain was prevalent and the third and fourth doses while the Alpha and Delta variants were prevalent in AUS and US. Local/systemic reactogenicity was assessed the day of vaccination and for 6 days thereafter. Unsolicited adverse events (AEs) were reported. Immunogenicity was measured before, and 14 days after, fourth dose administration, using anti-spike serum immunoglobulin G (IgG) and neutralization assays against ancestral SARS-CoV-2 strain and Omicron sublineages. Among 1283 enrolled participants, 258 were randomized to receive the two-dose primary series, of whom 104 received a third dose, and 45 received a fourth dose of NVX-CoV2373. The incidence of local/systemic reactogenicity events increased after the first three doses of NVX-CoV2373 and leveled off after dose 4. Unsolicited AEs were reported in 9 % of participants after dose 4 (none of which were severe or serious). Anti-rS IgG levels and neutralization antibody titers increased following booster doses to a level approximately four-fold higher than that observed after the primary series, with a progressively narrowed gap in response between the ancestral strain and Omicron BA.5. A fourth dose of NVX-CoV2373 enhanced immunogenicity for ancestral and variant SARS-CoV-2 strains without increasing reactogenicity, indicating that updates to the vaccine composition may not be currently warranted.

Safety and immunogenicity following a homologous booster dose of a SARS-CoV-2 recombinant spike protein vaccine (NVX-CoV2373): a secondary analysis of a randomised, placebo-controlled, phase 2 trial.

BACKGROUND: Emerging SARS-CoV-2 variants and evidence of waning vaccine efficacy present substantial obstacles towards controlling the COVID-19 pandemic. Booster doses of SARS-CoV-2 vaccines might address these concerns by amplifying and broadening the immune responses seen with initial vaccination regimens. We aimed to assess the immunogenicity and safety of a homologous booster dose of a SARS-CoV-2 recombinant spike protein vaccine (NVX-CoV2373). METHODS: This secondary analysis of a phase 2, randomised study assessed a single booster dose of a SARS-CoV-2 recombinant spike protein vaccine with Matrix-M adjuvant (NVX-CoV2373) in healthy adults aged 18-84 years, recruited from 17 clinical centres in the USA and Australia. Eligible participants had a BMI of 17-35 kg/m2 and, for women, were heterosexually inactive or using contraception. Participants who had a history of SARS-CoV or SARS-CoV-2, confirmed diagnosis of COVID-19, serious chronic medical conditions, or were pregnant or breastfeeding were excluded. Approximately 6 months following their primary two-dose vaccination series (administered day 0 and day 21), participants who received placebo for their primary vaccination series received a placebo booster (group A) and participants who received NVX-CoV2373 for their primary vaccination series (group B) were randomly assigned (1:1) again, via centralised interactive response technology system, to receive either placebo (group B1) or a single booster dose of NVX-CoV2373 (5 µg SARS-CoV-2 rS with 50 µg Matrix-M adjuvant; group B2) via intramuscular injection; randomisation was stratified by age and study site. Vaccinations were administered by designated site personnel who were masked to treatment assignment, and participants and other site staff were also masked. Administration personnel also assessed the outcome. The primary endpoints are safety (unsolicited adverse events) and reactogenicity (solicited local and systemic) events and immunogenicity (serum IgG antibody concentrations for the SARS-CoV-2 rS protein antigen) assessed 14 days after the primary vaccination series (day 35) and 28 days following booster (day 217). Safety was analysed in all participants in groups A, B1, and B2, according to the treatment received; immunogenicity was analysed in the per-protocol population (ie, participants in groups A, B1, and B2) who received all assigned doses and who did not test SARS-CoV-2-positive or received an authorised vaccine, analysed according to treatment assignment). This trial is registered with ClinicalTrials.gov, NCT04368988. FINDINGS: 1610 participants were screened from Aug 24, 2020, to Sept 25, 2020. 1282 participants were enrolled, of whom 173 were assigned again to placebo (group A), 106 were re-randomised to NVX-CoV2373-placebo (group B1), and 104 were re-randomised to NVX-CoV2373-NVX-CoV2373 (group B2); after accounting for exclusions and incorrect administration, 172 participants in group A, 102 in group B1, and 105 in group B2 were analysed for safety. Following the active booster, the proportion of participants with available data reporting local (80 [82%] of 97 participants had any adverse event; 13 [13%] had a grade ≥3 event) and systemic (75 [77%] of 98 participants had any adverse event; 15 [15%] had a grade ≥3 event) reactions was higher than after primary vaccination (175 [70%] of 250 participants had any local adverse event, 13 [5%] had a grade ≥3 event; 132 [53%] of 250 had any systemic adverse event, 14 [6%] had a grade ≥3 event). Local and systemic events were transient in nature (median duration 1·0-2·5 days). In the per-protocol immunogenicity population at day 217 (167 participants in group A, 101 participants in group B1, 101 participants in group B2), IgG geometric mean titres (GMT) had increased by 4·7-fold and MN50 GMT by 4·1-fold for the ancestral SARS-CoV-2 strain compared with the day 35 titres. INTERPRETATION: Administration of a booster dose of NVX-CoV2373 resulted in an incremental increase in reactogenicity. For both the prototype strain and all variants evaluated, immune responses following the booster were similar to or higher than those associated with high levels of efficacy in phase 3 studies of the vaccine. These data support the use of NVX-CoV2373 in booster programmes. FUNDING: Novavax and the Coalition for Epidemic Preparedness Innovations.

Small body size phenotypes among Middle and Later Stone Age Southern Africans.

Modern humans originated between 300 and 200 ka in structured populations throughout Africa, characterized by regional interaction and diversity. Acknowledgment of this complex Pleistocene population structure raises new questions about the emergence of phenotypic diversity. Holocene Southern African Later Stone Age (LSA) skeletons and descendant Khoe-San peoples have small adult body sizes that may reflect long-term adaptation to the Cape environment. Pleistocene Southern African adult body sizes are not well characterized, but some postcranial elements are available. The most numerous Pleistocene postcranial skeletal remains come from Klasies River Mouth on the Southern Cape coast of South Africa. We compare the morphology of these skeletal elements with globally sampled Holocene groups encompassing diverse adult body sizes and shapes (n = 287) to investigate whether there is evidence for phenotypic patterning. The adult Klasies River Mouth bones include most of a lumbar vertebra, and portions of a left clavicle, left proximal radius, right proximal ulna, and left first metatarsal. Linear dimensions, shape characteristics, and cross-sectional geometric properties of the Klasies River Mouth elements were compared using univariate and multivariate methods. Between-group principal component analyses group Klasies River Mouth elements, except the proximal ulna, with LSA Southern Africans. The similarity is driven by size. Klasies River Mouth metatarsal cross-sectional geometric properties indicate similar torsional and compressive strength to those from LSA Southern Africans. Phenotypic expressions of small-bodied adult morphology in Marine Isotope Stages 5 and 1 suggest this phenotype may represent local convergent adaptation to life in the Cape.

Disease as a Factor in the African Archaeological Record.

It is clear from their natural histories that various kinds of diseases would have affected African communities in the distant past. Climatic factors may have reduced the impact of plague-like epidemics across much of the continent. Because of the link between environment and disease vectors, the presence of a disease may have been a stimulus for some group movements in the African past. Evidence of the direct effects of diseases on human populations is generally elusive. Paleopathologists can identify some endemic diseases, but evidence from Africa is sparse. Paleogenomics research can also identify some (not all) endemic and epidemic disease vectors. Recent African aDNA discoveries of inherited resistance to endemic diseases suggest that future paleogenomic research may help us learn much more about the impact of diseases on the African past.

Il ressort clairement de leur histoire naturelle que divers types de maladies auraient affecté les communautés africaines dans un passé lointain. Les facteurs climatiques peuvent avoir réduit l'impact des épidémies de type peste sur une grande partie du continent. En raison du lien entre l'environnement et les vecteurs de maladies, la présence d'une maladie peut avoir été un stimulant pour certains mouvements de groupe dans le passé africain. Les preuves des effets directs des maladies sur les populations humaines sont généralement insaisissables. Les paléopathologistes peuvent identifier certaines maladies endémiques, mais les preuves provenant d'Afrique sont rares. La recherche en paléogénomique peut également identifier certains (pas tous) des vecteurs de maladies endémiques et épidémiques. Les découvertes récentes de l'ADN fossile en Afrique sur la résistance héréditaire aux maladies endémiques suggèrent que les futures recherches paléogénomiques pourraient nous aider à en apprendre beaucoup plus sur l'impact des maladies sur le passé africain.

A Late Holocene community burial area: Evidence of diverse mortuary practices in the Western Cape, South Africa.

Over several decades, human skeletal remains from at least twelve individuals (males, females, children and infants) were recovered from a small area (ca. 10 x 10 m) on the eastern shore of Table Bay, Cape Town, near the mouth of the Diep River where it empties into the sea. Two groups, each comprising four individuals, appear to have been buried in single graves. Unusually for this region, several skeletons were interred with large numbers of ostrich eggshell (OES) beads. In some cases, careful excavation enabled recovery of segments of beadwork. One collective burial held items including an ostrich egg-shell flask, a tortoise carapace bowl, a fragmentary bone point or linkshaft and various lithic artefacts. This group appears to have died together and been buried expediently. A mid-adult woman from this group sustained perimortem blunt-force trauma to her skull, very likely the cause of her death. This case adds to the developing picture of interpersonal violence associated with a period of subsistence intensification among late Holocene foragers. Radiocarbon dates obtained for nine skeletons may overlap but given the uncertainties associated with marine carbon input, we cannot constrain the date range more tightly than 1900-1340 calBP (at 2 sigma). The locale appears to have been used by a community as a burial ground, perhaps regularly for several generations, or on a single catastrophic occasion, or some combination thereof. The evidence documents regional and temporal variation in burial practices among late Holocene foragers of the south-western Cape.

Trends in height, weight, BMI, skinfolds, and measures of overweight and obesity from 1979 through 1999 among American Indian Youth: The Akwesasne Mohawk.

BACKGROUND/OBJECTIVES: Information on recent changes in overweight, obesity, and adiposity among American Indians is scarce. To assess changes in size and adiposity among American Indian youth, data from two samples of Akwesasne Mohawk youth, were compared. SUBJECTS/METHODS: Both project 1, conducted in 1979 (n = 75) and Project 2, conducted between 1996 and 1999 (n = 206), sampled youth 10-14 years of age from the Akwesasne Mohawk Reservation (aka St. Regis) that borders New York state, and Ontario and Quebec provinces. Heights, weights, and skinfold thicknesses were converted to z-scores using CDC reference values. BMI status was calculated in terms of WHO age-specific cutoffs and CDC cutoffs. RESULTS: z-Scores for heights differed little between projects. The between-project difference in weight z-score is twice the between-project z-score difference for height. Differences among males are larger and more often significant. Triceps and subscapular skinfold thickness are significantly greater in Project 2. The rate of overweight and obesity combined, increased 3.3-fold. In multiple regression analyses with sex, height, and age in the model, project is a significant predictor of weight and skinfolds. CONCLUSIONS: Weight and adiposity have increased substantially from 1979 to 1996-99. Overweight and obesity became significantly more common. Given the increase in adiposity, these youth may be facing significant health risks as adults in terms of cardiovascular disease, cancer, and type II diabetes unless weight and adiposity is reduced.

Ontogenetic changes to bone microstructure in an archaeologically derived sample of human ribs.

There is considerable variation in the gross morphology and tissue properties among the bones of human infants, children, adolescents, and adults. Using 18 known-age individuals (nfemale  = 8, nmale  = 9, nunknown  = 1; birth to 21 years old), from a well-documented cemetery collection, Spitalfields Christ Church, London, UK, this study explores growth-related changes in cortical and trabecular bone microstructure. Micro-CT scans of mid-shaft middle thoracic ribs are used for quantitative analysis. Results are then compared to previously quantified conventional histomorphometry of the same sample. Total area (Tt.Ar), cortical area (Ct.Ar), cortical thickness (Ct.Th), and the major (Maj.Dm) and minor (Min.Dm) diameters of the rib demonstrate positive correlations with age. Pore density (Po.Dn) increases, but age-related changes to cortical porosity (Ct.Po) appear to be non-linear. Trabecular thickness (Tb.th) and trabecular separation (Tb.Sp) increase with age, whereas trabecular bone pattern factor (Tb.Pf), structural model index (SMI), and connectivity density (Conn.D) decrease with age. Sex-based differences were not identified for any of the variables included in this study. Some samples display clear evidence of diagenetic alteration without corresponding changes in radiopacity, which compromises the reliability of bone mineral density (BMD) data in the study of past populations. Cortical porosity data are not correlated with two-dimensional measures of osteon population density (OPD). This suggests that unfilled resorption spaces contribute more significantly to cortical porosity than do the Haversian canals of secondary osteons. Continued research using complementary imaging techniques and a wide array of histological variables will increase our understanding of age- and sex-specific ontogenetic patterns within and among human populations.

Diet and adult age-at-death among mobile foragers: A synthesis of bioarcheological methods.

OBJECTIVES: The research explores whether the combined study of cortical bone histology, bone morphology, and dietary stable isotopes can expand insights into past human health and adaptations, particularly dietary sufficiency and life span. MATERIALS AND METHODS: Midthoracic rib cortices from 54 South African Late Holocene adult skeletons (28 M, 24 F, two sex undetermined) are assessed by transmitted-light microscopy for cross-sectional area measurements, osteon area (On.Ar), osteon population density, and presence/absence of secondary osteon variants. Values for δ13 Cbone collagen , δ15 Nbone collagen , 14 C dates, Southwestern and Southern Cape geographic regions, body size measures, estimated ages-at-death from both morphological and histological methods are integrated into analyses, which include Spearman correlations, χ2 tests and Kruskal-Wallis ANOVAs. RESULTS: There is reduced On.Ar variability with higher δ15 N (r = -.41, p = .005); rib %cortical area and δ15 N are negatively correlated in the Southern Cape group (r = -.60, p = .03). Osteon variants are more common in older adults; histological ages at death are significantly older than those determined from gross morphology. DISCUSSION: We found bone tissue relationships with measures of diet composition, but indicators of dietary adequacy remain elusive. Relationships of tissue quality and isotopes suggest that some Southern Cape adults lived long lives. Osteon variants are associated with age-at-death; some association with diet remains possible. Gross morphological methods appear to underestimate adult ages-at-death, at least among small-bodied adults.

Use of backscattered scanning electron microscopy to quantify the bone tissues of midthoracic human ribs.

OBJECTIVES: Novel information on apartheid health conditions may be obtained through the study of recent skeletal collections. Using a backscattered scanning electron microscopy (BSE-SEM) approach, this study aims to produce bone quality and tissue mineralization data for an understudied South African population from the Western Cape province. METHODS: Using BSE-SEM imaging, cortical porosity (Ct.Po), osteocyte lacunar density (Ot.Lc.Dn), and the degree of tissue mineralization were quantified in midthoracic ribs from the Kirsten Skeletal Collection. Individuals ( n female = 75, n male = 68, and mean age = 46.3 years) were predominantly from the South Africa Colored (SAC) population group ( n SAC = 103, 72%). Full cross-sectional images of each rib were manually stitched together in Adobe Photoshop. Photomontages were imported into MATALB (Mathworks, Natick, MA) for image processing and analysis. Age-related changes in histomorphometric parameters and sex differences were examined using correlation analysis, as well as linear and nonlinear regressions. RESULTS: Young adult men have significantly less mineralized bone and fewer osteocyte lacunae, compared to women. Only men demonstrate a significant negative relationship between Ot.Lc.Dn and age. Average tissue mineralization decreases with age in women, while Ct.Po increases. Pore area (Po.Ar) does not vary with age, but pore density (Po.Dn) is highest in the perimenopause, when accelerated rates of bone turnover are first anticipated. Ct.Po is highest in the years following the predicted age of menopause, but levels off in the final decades of life. CONCLUSIONS: Men and women display disparate patterns of bone aging. Systemic disenfranchisement of non-white population groups affected bone health in South Africa, and may continue to do so today. Indicators of poor bone quality are evident in the full study sample, indicating that osteoporosis and fracture risk are not just of concern to the aged white female population.

The bioarchaeology of mid-Holocene pastoralist cemeteries west of Lake Turkana, Kenya.

Early herders in eastern Africa built elaborate megalithic cemeteries ~ 5000 BP overlooking what is now Lake Turkana in northwestern Kenya. At least six 'pillar sites' were constructed during a time of rapid change: cattle, sheep, and goats were introduced to the basin as the lake was shrinking at the end of the African Humid Period. Cultural changes at this time include new lithic and ceramic technologies and the earliest monumentality in eastern Africa. Isolated human remains previously excavated from pillar sites east of Lake Turkana seemed to indicate that pillar site platforms were ossuaries for secondary burials. Recent bioarchaeological excavations at four pillar sites west of the lake have now yielded ≥49 individuals, most from primary and some from secondary interments, challenging earlier interpretations. Here we describe the mortuary cavities, and burial contexts, and included items such as adornments from Lothagam North, Lothagam West, Manemanya, and Kalokol pillar sites. In doing so, we reassess previous hypotheses regarding pillar site construction, use, and inter-site variability. We also present the first osteological analyses of skeletons buried at these sites. Although the human remains are fragmentary, they are nevertheless informative about the sex, age, and body size of the deceased and give evidence for health and disease processes. Periosteal moulds of long bone midshafts (n = 34 elements) suggest patterns of terrestrial mobility. Pillar site deposits provide important new insights into early herder lifeways in eastern Africa and the impact of the transition to pastoralism on past human populations.

The people behind the samples: Biographical features of Past Hunter-Gatherers from KwaZulu-Natal who yielded aDNA.

PURPOSE: Skeletons sampled for ancient human DNA analysis are sometimes complete enough to provide information about the lives of the people they represent. We focus on three Later Stone Age skeletons, ca. 2000 B.P., from coastal KwaZulu-Natal, South Africa, whose ancient genomes have been sequenced (Schlebusch et al., 2017). METHODS: Bioarchaeological approaches are integrated with aDNA information. RESULTS: All skeletons are male. Dental development shows that the boy, with prominent cribra orbitalia, died at age 6-7 years. Two men show cranial and spinal trauma, extensive tooth wear, plus mild cribra orbitalia in one. CONCLUSIONS: Dental wear and trauma of the adults are consistent with hunter-gatherer lives. Even partial aDNA evidence contributes to sex determination. Parasitic infection such as schistosomiasis is the best-fit cause for the child's anemia in this case. CONTRIBUTION TO KNOWLEDGE: The convergence of genomic and bioarchaeological approaches expands our knowledge of the past lives of a boy and two men whose lives as hunter-gatherers included episodes of trauma and disease. LIMITATIONS: The skeletons are incomplete, in variable condition, and from poorly characterized local cultural contexts. SUGGESTIONS FOR FURTHER RESEARCH: Thorough osteobiographic analysis should accompany paleogenomic investigations. Such disciplinary collaboration enriches our understanding of the human past.

The Influence of Body Size and Bone Mass on Cortical Bone Histomorphometry in Human Ribs.

This study examines the influence of human adult body size and bone mass on cortical bone histomorphometry, and explores microstructural variation in mid-thoracic ribs. The sample consists of 213 individuals (n female = 82, n male = 131, mean age-at-death = 47.96 ± 15.71 years) from the Kirsten Skeletal Collection, Stellenbosch University, South Africa. Maximum femur length and femur maximum head diameter are used as proxies for height and weight; total cross-sectional area, endosteal area, and cortical area are used to derive measures of bone mass. Histomorphometric variables include osteon population density (OPD) and osteon area (On.Ar). Partial correlations, controlling for age, test for significant relationships among variables. A hierarchical regression model is used to determine unique variable contributions to On.Ar and OPD. Body size measurements do not correlate with either bone mass or histomorphometric variables, suggesting that size-standardization may not be necessary in studies of rib bone microstructure. Age is the most significant factor affecting OPD, while OPD is the best predictor of On.Ar. These findings suggest that age-related secondary osteon crowding affects osteon geometry. Understanding the biological mechanisms that direct bone remodeling and determine microstructural variation is essential for interpreting histological data. Anat Rec, 301:1788-1796, 2018. © 2018 Wiley Periodicals, Inc.

A monumental cemetery built by eastern Africa's first herders near Lake Turkana, Kenya.

Monumental architecture is a prime indicator of social complexity, because it requires many people to build a conspicuous structure commemorating shared beliefs. Examining monumentality in different environmental and economic settings can reveal diverse reasons for people to form larger social units and express unity through architectural display. In multiple areas of Africa, monumentality developed as mobile herders created large cemeteries and practiced other forms of commemoration. The motives for such behavior in sparsely populated, unpredictable landscapes may differ from well-studied cases of monumentality in predictable environments with sedentary populations. Here we report excavations and ground-penetrating radar surveys at the earliest and most massive monumental site in eastern Africa. Lothagam North Pillar Site was a communal cemetery near Lake Turkana (northwest Kenya) constructed 5,000 years ago by eastern Africa's earliest pastoralists. Inside a platform ringed by boulders, a 119.5-m2 mortuary cavity accommodated an estimated minimum of 580 individuals. People of diverse ages and both sexes were buried, and ornaments accompanied most individuals. There is no evidence for social stratification. The uncertainties of living on a "moving frontier" of early herding-exacerbated by dramatic environmental shifts-may have spurred people to strengthen social networks that could provide information and assistance. Lothagam North Pillar Site would have served as both an arena for interaction and a tangible reminder of shared identity.

A juvenile with compromised osteogenesis provides insights into past hunter-gatherer lives.

The Late Archaic in northeastern North America (4500-2800 B.P.) pre-dates reliance on pottery and domesticated plants. It is thought to reflect a highly mobile, seasonal migratory foraging/hunting regimen. A juvenile skeleton with pervasive bone wasting and fragile jaws from the Hind Site (AdHk-1), ca. 3000 B.P., southwestern Ontario, provides evidence of the social context of her family group, including aspects of mobility and food management. The well-preserved bones and teeth are considered in bioarchaeological context. Radiographic, osteometric and cross-sectional geometric approaches to assessing musculoskeletal function are presented, plus differential diagnosis of the bone wasting condition. All bones of the probable female (aged approx. 16yr) show stunting and wasting. Wedged lower vertebral bodies, porous trabeculae, undeveloped bicondylar angles (femur) and abnormally low cortical long bone mass are consistent with chronically reduced ambulation. Few teeth remain in the dramatically resorbed alveoli; slight tooth wear and substantial calculus suggest a modified (soft) diet. Osteogenesis imperfecta type IV is the most probable etiology. The extended survival of this juvenile who may never have walked reflects collective care. The case provides evidence of a past lifeway that appears to have been organized around logistic mobility, including occupational stability and food storage.

Sex-specific patterns in cortical and trabecular bone microstructure in the Kirsten Skeletal Collection, South Africa.

OBJECTIVES: The purpose of this study was to provide bone histomorphometric reference data for South Africans of the Western Cape who likely dealt with health issues under the apartheid regime. METHODS: The 206 adult individuals (n female = 75, n male = 131, mean = 47.9 ± 15.8 years) from the Kirsten Skeletal Collection, U. Stellenbosch, lived in the Cape Town metropole from the late 1960s to the mid-1990s. To study age-related changes in cortical and trabecular bone microstructure, photomontages of mid-thoracic rib cross-sections were quantitatively examined. Variables include relative cortical area (Rt.Ct.Ar), osteon population density (OPD), osteon area (On.Ar), bone volume fraction (BV/TV), trabecular number (Tb.N), trabecular thickness (Tb.Th), and trabecular spacing (Tb.Sp). RESULTS: All cortical variables demonstrated significant relationships with age in both sexes, with women showing stronger overall age associations. Peak bone mass was compromised in some men, possibly reflecting poor nutritional quality and/or substance abuse issues throughout adolescence and early adulthood. In women, greater predicted decrements in On.Ar and Rt.Ct.Ar suggest a structural disadvantage with age, consistent with postmenopausal bone loss. Age-related patterns in trabecular bone microarchitecture are variable and difficult to explain. Except for Tb.Th, there are no statistically significant relationships with age in women. Men demonstrate significant negative correlations between BV/TV, Tb.N, and age, and a significant positive correlation between Tb.Sp and age. CONCLUSIONS: This research highlights sex-specific differences in patterns of age-related bone loss, and provides context for discussion of contemporary South African bone health. While the study sample demonstrates indicators of poor bone quality, osteoporosis research continues to be under-prioritized in South Africa.

The efficacy of cognitive interventions for improving cognitive performance and academic achievement in children after cancer treatment: A systematic review.

Academic decline has been reported in children after cancer treatment, believed to be as a result of cognitive impairment. Cognitive interventions may improve both the present and future outcomes for children after cancer treatment by improving cognitive and/or academic performance. This review aimed to examine the efficacy of cognitive interventions in children who had received cancer treatment. A systematic search of the PsycInfo and PubMed databases was conducted in May 2015 to identify studies in which cognitive interventions were conducted with children who had undergone cancer treatment and were under the age of 21. Cognitive or academic outcomes needed to be reported pre- and post-intervention to meet the inclusion criteria. Eleven studies were included in this review. Computerized and home-based cognitive interventions were found to be most successful at improving cognitive skills. However, few cognitive interventions assessed academic achievement specifically. Future cognitive intervention research studies should include measures of academic achievement outcomes, because academic achievement and cognitive outcomes may differ. Future research regarding the effectiveness of early, home-based and computerized intervention is warranted.

Cancer-related cognitive impairment in children.

PURPOSE OF REVIEW: To review recent research on cancer-related cognitive impairment (CRCI) in children, including correlational studies and interventions in which outcomes have included cognitive test performance, neuroimaging or academic performance. RECENT FINDINGS: Impairments in processing speed, working memory, executive function and attention continue to be demonstrated in survivors of childhood cancers. Children receiving radiation treatment for their cancer demonstrate greater impairment than those who undergo surgery and/or chemotherapy without radiation. However, CRCI still occurs in the absence of radiation treatment, particularly in the domain of attention. Recent neuroimaging studies highlight atypical connectivity of white matter and its associations with cognitive performance. Given impairments in cognitive function and associated neuroanatomical factors, it is not surprising that survivors of childhood cancers experience academic difficulties. However, early intervention may provide one means of improving cognitive and academic outcomes. SUMMARY: Children with cancer are at risk of impairment in the domains of processing speed, attention, working memory and executive function. Those who receive radiation are likely to experience greater CRCI than those who do not receive this treatment. All survivors of childhood cancers should be carefully monitored to provide support and implement evidence-based interventions to ameliorate cognitive late effects.

Cortical bone histomorphology of known-age skeletons from the Kirsten collection, Stellenbosch university, South Africa.

OBJECTIVES: Normal human bone tissue changes predictably as adults get older, but substantial variability in pattern and pace remains unexplained. Information is needed regarding the characteristics of histological variables across diverse human populations. METHODS: Undecalcified thin sections from mid-thoracic ribs of 213 skeletons (138 M, 75 F, 17-82 years, mean age 48 years), are used to explore the efficacy of an established age-at-death estimation method and methodological approach (Cho et al.: J Forensic Sci 47 (2002) 12-18) and expand on it. The ribs are an age-balanced sample taken from skeletonized cadavers collected from 1967 to 1999 in South Africa, each with recorded sex, age, cause of death and government-defined population group (129 "Colored," 49 "Black," 35 "White"). RESULTS: The Ethnicity Unknown equation performs better than those developed for European-Americans and African-Americans, in terms of accuracy and bias. A new equation based solely on the study sample does not improve accuracy. Osteon population densities (OPD) show predicted values, yet secondary osteon areas (On.Ar) are smaller than expected for non-Black subgroups. Relative cortical area (Ct.Ar/Tt.Ar) is low among non-Whites. CONCLUSIONS: Results from this highly diverse sample show that population-specific equations do not increase estimate precision. While within the published range of error for the method (±24.44 years), results demonstrate a systematic under-aging of young adults and over-aging of older adults. The regression approach is inappropriate. The field needs fresh approaches to statistical treatment and to factors behind cortical bone remodeling.