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  1. Curnoe D, Datan I, Zhao JX, Leh Moi Ung C, Aubert M, Sauffi MS, et al.
    PLoS One, 2018;13(6):e0196633.
    PMID: 29874227 DOI: 10.1371/journal.pone.0196633
    The skeletal remains of Late Pleistocene-early Holocene humans are exceptionally rare in island Southeast Asia. As a result, the identity and physical adaptations of the early inhabitants of the region are poorly known. One archaeological locality that has historically been important for understanding the peopling of island Southeast Asia is the Niah Caves in the northeast of Borneo. Here we present the results of direct Uranium-series dating and the first published descriptions of three partial human mandibles from the West Mouth of the Niah Caves recovered during excavations by the Harrissons in 1957. One of them (mandible E/B1 100") is somewhat younger than the 'Deep Skull' with a best dating estimate of c30-28 ka (at 2σ), while the other two mandibles (D/N5 42-48" and E/W 33 24-36") are dated to a minimum of c11.0-10.5 ka (at 2σ) and c10.0-9.0 ka (at 2σ). Jaw E/B1 100" is unusually small and robust compared with other Late Pleistocene mandibles suggesting that it may have been ontogenetically altered through masticatory strain under a model of phenotypic plasticity. Possible dietary causes could include the consumption of tough or dried meats or palm plants, behaviours which have been documented previously in the archaeological record of the Niah Caves. Our work suggests a long history back to before the LGM of economic strategies involving the exploitation of raw plant foods or perhaps dried and stored meat resources. This offers new insights into the economic strategies of Late Pleistocene-early Holocene hunter-gatherers living in, or adjacent to, tropical rainforests.
  2. Schratz A, Pineda MF, Reforma LG, Fox NM, Le Anh T, Tommaso Cavalli-Sforza L, et al.
    Adv Parasitol, 2010;72:79-107.
    PMID: 20624529 DOI: 10.1016/S0065-308X(10)72004-2
    Ethnic minority groups (EMGs) are often subject to exclusion, marginalization and poverty. These characteristics render them particularly vulnerable to neglected diseases, a diverse group of diseases that comprise bacteria, ecto-parasites, fungi, helminths and viruses. Despite the health policy relevance, only little is known of the epidemiological profile of neglected diseases among EMGs. We reviewed country data from Australia, Cambodia, Lao People's Democratic Republic, Malaysia, the Philippines and Vietnam and found several overlaps between regions with high proportions of EMG population and high prevalence rates of neglected diseases (infections with soil-transmitted helminths, filarial worms, schistosomes, food-borne trematodes and cestodes). While the links are not always clearly evident and it is impossible to establish correlations among highly aggregated data without control variables-such as environmental factors-there appear indeed to be important linkages between EMGs, socio-economic status and prevalence of neglected diseases. Some determinants under consideration are lack of access to health care and general health status, poverty and social marginalization, as well as education and literacy. Further research is needed to deepen the understanding of these linkages and to determine their public health and socio-economic significance. In particular, there is a need for more data from all countries in the Western Pacific Region that is disaggregated below the provincial level. Selected case studies that incorporate other control variables-such as risk factors from the physical environment-might be useful to inform policy makers about the feasibility of prevention and control interventions that are targeted at high-risk EMGs.
  3. Burtness B, Harrington KJ, Greil R, Soulières D, Tahara M, de Castro G, et al.
    Lancet, 2019 11 23;394(10212):1915-1928.
    PMID: 31679945 DOI: 10.1016/S0140-6736(19)32591-7
    BACKGROUND: Pembrolizumab is active in head and neck squamous cell carcinoma (HNSCC), with programmed cell death ligand 1 (PD-L1) expression associated with improved response.

    METHODS: KEYNOTE-048 was a randomised, phase 3 study of participants with untreated locally incurable recurrent or metastatic HNSCC done at 200 sites in 37 countries. Participants were stratified by PD-L1 expression, p16 status, and performance status and randomly allocated (1:1:1) to pembrolizumab alone, pembrolizumab plus a platinum and 5-fluorouracil (pembrolizumab with chemotherapy), or cetuximab plus a platinum and 5-fluorouracil (cetuximab with chemotherapy). Investigators and participants were aware of treatment assignment. Investigators, participants, and representatives of the sponsor were masked to the PD-L1 combined positive score (CPS) results; PD-L1 positivity was not required for study entry. The primary endpoints were overall survival (time from randomisation to death from any cause) and progression-free survival (time from randomisation to radiographically confirmed disease progression or death from any cause, whichever came first) in the intention-to-treat population (all participants randomly allocated to a treatment group). There were 14 primary hypotheses: superiority of pembrolizumab alone and of pembrolizumab with chemotherapy versus cetuximab with chemotherapy for overall survival and progression-free survival in the PD-L1 CPS of 20 or more, CPS of 1 or more, and total populations and non-inferiority (non-inferiority margin: 1·2) of pembrolizumab alone and pembrolizumab with chemotherapy versus cetuximab with chemotherapy for overall survival in the total population. The definitive findings for each hypothesis were obtained when statistical testing was completed for that hypothesis; this occurred at the second interim analysis for 11 hypotheses and at final analysis for three hypotheses. Safety was assessed in the as-treated population (all participants who received at least one dose of allocated treatment). This study is registered at ClinicalTrials.gov, number NCT02358031.

    FINDINGS: Between April 20, 2015, and Jan 17, 2017, 882 participants were allocated to receive pembrolizumab alone (n=301), pembrolizumab with chemotherapy (n=281), or cetuximab with chemotherapy (n=300); of these, 754 (85%) had CPS of 1 or more and 381 (43%) had CPS of 20 or more. At the second interim analysis, pembrolizumab alone improved overall survival versus cetuximab with chemotherapy in the CPS of 20 or more population (median 14·9 months vs 10·7 months, hazard ratio [HR] 0·61 [95% CI 0·45-0·83], p=0·0007) and CPS of 1 or more population (12·3 vs 10·3, 0·78 [0·64-0·96], p=0·0086) and was non-inferior in the total population (11·6 vs 10·7, 0·85 [0·71-1·03]). Pembrolizumab with chemotherapy improved overall survival versus cetuximab with chemotherapy in the total population (13·0 months vs 10·7 months, HR 0·77 [95% CI 0·63-0·93], p=0·0034) at the second interim analysis and in the CPS of 20 or more population (14·7 vs 11·0, 0·60 [0·45-0·82], p=0·0004) and CPS of 1 or more population (13·6 vs 10·4, 0·65 [0·53-0·80], p<0·0001) at final analysis. Neither pembrolizumab alone nor pembrolizumab with chemotherapy improved progression-free survival at the second interim analysis. At final analysis, grade 3 or worse all-cause adverse events occurred in 164 (55%) of 300 treated participants in the pembrolizumab alone group, 235 (85%) of 276 in the pembrolizumab with chemotherapy group, and 239 (83%) of 287 in the cetuximab with chemotherapy group. Adverse events led to death in 25 (8%) participants in the pembrolizumab alone group, 32 (12%) in the pembrolizumab with chemotherapy group, and 28 (10%) in the cetuximab with chemotherapy group.

    INTERPRETATION: Based on the observed efficacy and safety, pembrolizumab plus platinum and 5-fluorouracil is an appropriate first-line treatment for recurrent or metastatic HNSCC and pembrolizumab monotherapy is an appropriate first-line treatment for PD-L1-positive recurrent or metastatic HNSCC.

    FUNDING: Merck Sharp & Dohme.

  4. Vilizzi L, Copp GH, Hill JE, Adamovich B, Aislabie L, Akin D, et al.
    Sci Total Environ, 2021 Sep 20;788:147868.
    PMID: 34134389 DOI: 10.1016/j.scitotenv.2021.147868
    The threat posed by invasive non-native species worldwide requires a global approach to identify which introduced species are likely to pose an elevated risk of impact to native species and ecosystems. To inform policy, stakeholders and management decisions on global threats to aquatic ecosystems, 195 assessors representing 120 risk assessment areas across all six inhabited continents screened 819 non-native species from 15 groups of aquatic organisms (freshwater, brackish, marine plants and animals) using the Aquatic Species Invasiveness Screening Kit. This multi-lingual decision-support tool for the risk screening of aquatic organisms provides assessors with risk scores for a species under current and future climate change conditions that, following a statistically based calibration, permits the accurate classification of species into high-, medium- and low-risk categories under current and predicted climate conditions. The 1730 screenings undertaken encompassed wide geographical areas (regions, political entities, parts thereof, water bodies, river basins, lake drainage basins, and marine regions), which permitted thresholds to be identified for almost all aquatic organismal groups screened as well as for tropical, temperate and continental climate classes, and for tropical and temperate marine ecoregions. In total, 33 species were identified as posing a 'very high risk' of being or becoming invasive, and the scores of several of these species under current climate increased under future climate conditions, primarily due to their wide thermal tolerances. The risk thresholds determined for taxonomic groups and climate zones provide a basis against which area-specific or climate-based calibrated thresholds may be interpreted. In turn, the risk rankings help decision-makers identify which species require an immediate 'rapid' management action (e.g. eradication, control) to avoid or mitigate adverse impacts, which require a full risk assessment, and which are to be restricted or banned with regard to importation and/or sale as ornamental or aquarium/fishery enhancement.
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