Reflex genetic testing of tumor tissue is being completed to direct cancer treatment; however, the patient impact of this genetic testing model is unknown. This survey study evaluates psychological ...outcomes following tumor and germline genetic testing in individuals with a new diagnosis of high‐grade serous ovarian cancer (HGSOC). Individuals were recruited from two hospitals in Toronto, Canada. Participants completed surveys 1 week after receiving tumor results and 1 week after receiving germline results (which included genetic counseling). Outcomes included cancer‐related distress (Impact of Events Scale: IES), genetic testing‐related distress (Multidimensional Impact of Cancer Risk Assessment: MICRA), and patient satisfaction. Paired t‐tests were used to evaluate differences in outcomes following each genetic test result; Cohen's d was used to evaluate effect size. Subgroup analyses were undertaken according to age at diagnosis (<60 years vs. ≥60 years) and test results (any positive vs. both negative). McNemar's test assessed differences in satisfaction. Fifty‐two individuals were included in the analyses. Mean IES scores were similar following disclosure of tumor and germline results (27.39 vs. 26.14; p = 0.481; d = 0.101). Compared to following tumor result disclosure, MICRA scores were significantly lower following receipt of germline results with genetic counseling (27.23 vs. 22.69; p = 0.007; d = 0.435). Decreases in MICRA scores from tumor to germline result disclosure were greater for those diagnosed <60 years or those who received only negative test results. Most individuals were satisfied/highly satisfied following tumor (85.7%) and germline (89.8%) results disclosure (p = 0.774). Reflex tumor, and subsequent germline, genetic testing is a new model of care for cancer patients. In our cohort, genetic testing‐related distress decreased significantly following receipt of germline results with genetic counseling, especially for individuals diagnosed under 60 years and those receiving only negative results. Most individuals were satisfied with this model of care.
Evidence for climatic change across the North American Monsoon (NAM) and adjacent areas is reviewed, drawing on continental and marine records and the application of climate models. Patterns of ...change at 12,000, 9000, 6000 and 4000 cal yr BP are presented to capture the nature of change from the Younger Dryas (YD) and through the mid-Holocene. At the YD, conditions were cooler overall, wetter in the north and drier in the south, while moving into the Holocene wetter conditions became established in the south and then spread north as the NAM strengthened. Until c. 8000 cal yr BP, the Laurentide Ice Sheet influenced precipitation in the north by pushing the Bermuda High further south. The peak extent of the NAM seems to have occurred around 6000 cal yr BP. 4000 cal yr BP marks the start of important changes across the NAM region, with drying in the north and the establishment of the clear differences between the summer-rain dominated south and central areas and the north, where winter rain is more important. This differentiation between south and north is crucial to understanding many climate responses across the NAM. This increasing variability is coincident with the declining influence of orbital forcing. 4000 cal yr BP also marks the onset of significant anthropogenic activity in many areas. For the last 2000 years, the focus is on higher temporal resolution change, with strong variations across the region. The Medieval Climate Anomaly (MCA) is characterised by centennial scale ‘megadrought’ across the southwest USA, associated with cooler tropical Pacific SSTs and persistent La Niña type conditions. Proxy data from southern Mexico, Central America and the Caribbean reveal generally wetter conditions, whereas records from the highlands of central Mexico and much of the Yucatan are typified by long -term drought. The Little Ice Age (LIA), in the north, was characterised by cooler, wetter winter conditions that have been linked with increased frequency of El Niño's. Proxy records in the central and southern regions reveal generally dry LIA conditions, consistent with cooler SSTs in the Caribbean and Gulf of Mexico. This synthesis demonstrates that in some periods, one major forcing can dominate across the whole area (e.g. insolation in the early-mid Holocene), but at other times there is strong variability in patterns of change due to the differential impact of forcings such as the Pacific Decadal Oscillation (PDO) and the Atlantic Multidecadal Oscillation (AMO) on precipitation seasonality.
•Continental and marine Holocene records of the North American Monsoon (NAM) are examined.•Maps of change at 12,000, 9000, 6000, 4000 cal yr BP and for the MCA and LIA are presented.•Changes over the last 2000 years, including the MCA and LIA are reviewed.•Potential forcings are considered showing a modified response to insolation through to the mid Holocene.•From ca 4000 cal BP other forcings dominate and the modern regime becomes established.
Oral immunotherapy is effective at inducing desensitisation to allergens and induces sustained unresponsiveness (ie, clinical remission) in a subset of patients, but causes frequent reactions. We ...aimed to investigate whether addition of a probiotic adjuvant improved the efficacy or safety of peanut oral immunotherapy.
PPOIT-003, a multicentre, randomised, phase 2b trial, was conducted in three tertiary hospitals in Australia (Adelaide SA, Melbourne VIC, and Perth WA) in children aged 1-10 years, weighing more than 7 kg, with peanut allergy confirmed by a double-blind placebo-controlled food challenge (cumulative 4950 mg dose of peanut protein) and positive peanut skin prick test (≥3 mm) or peanut-specific IgE (≥0·35 kU/L). Children were randomly assigned (2:2:1) to receive probiotic and peanut oral immunotherapy (PPOIT), placebo probiotic and peanut oral immunotherapy (OIT), or placebo probiotic and placebo OIT (placebo) for 18 months, and were followed up until 12 months after completion of treatment. Oral immunotherapy consisted of increasing doses of peanut protein (commercially available food-grade 12% defatted peanut flour 50% peanut protein) until a 2000 mg daily maintenance dose was reached. The probiotic adjuvant was a daily dose of 2 × 10
colony-forming units of the probiotic Lactobacillus rhamnosus ATCC 53103. Placebo immunotherapy comprised maltodextrin, brown food colouring, and peanut essence, and placebo probiotic was maltodextrin. Dual primary outcomes were 8-week sustained unresponsiveness, defined as no reaction to a cumulative dose of 4950 mg peanut protein at treatment completion and 8 weeks after treatment completion, in the PPOIT versus placebo groups and the PPOIT versus OIT groups, analysed by intention to treat. Safety endpoints were adverse events during the treatment phase, and peanut ingestion and reactions in the 12-month post-treatment period. This study is registered with the Australian New Zealand Clinical Trials Registry, 12616000322437.
Between July 4, 2016, and Sept 21, 2020, 201 participants were enrolled and included in the intention-to-treat analysis. 36 (46%) of 79 children in the PPOIT group and 42 (51%) of 83 children in the OIT group achieved sustained unresponsiveness compared with two (5%) of 39 children in the placebo group (risk difference 40·44% 95% CI 27·46 to 53·42 for PPOIT vs placebo, p<0·0001), with no difference between PPOIT and OIT (-5·03% -20·40 to 10·34, p=0·52). Treatment-related adverse events were reported in 72 (91%) of 79 children in the PPOIT group, 73 (88%) of 83 children in the OIT group, and 28 (72%) of 39 children in the placebo group. Exposure-adjusted incidence of adverse events was 10·58 in the PPOIT group, 11·36 in the OIT, and 2·09 in the placebo group (ratio 0·92 95% CI 0·85 to 0·99 for PPOIT vs OIT, p=0·042; 4·98 4·11-6·03 for PPOIT vs placebo, p<0·0001; 5·42 4·48-6·56 for OIT vs placebo, p<0·0001), with differences seen primarily in gastrointestinal symptoms and in children aged 1-5 years. During the 12-month post-treatment period, 60 (85%) of 71 participants in the PPOIT group, 60 (86%) of 70 participants in the OIT group, and six (18%) of 34 participants in the placebo group were eating peanut; rescue epinephrine use was infrequent (two 3% of 71 in the PPOIT group, four 6% of 70 in the OIT group, and none in the placebo group).
Both PPOIT and OIT were effective at inducing sustained unresponsiveness. Addition of a probiotic did not improve efficacy of OIT, but might offer a safety benefit compared with OIT alone, particularly in preschool children.
National Health and Medical Research Council Australia and Prota Therapeutics.
Reflex (automatic) BRCA1 and BRCA2 (BRCA1/2) genetic testing of tumour tissue is being completed for all newly diagnosed high-grade serous ovarian cancer (HGSOC) in the province of Ontario, Canada. ...The objective of this study was to measure the psychological impact of tumour genetic testing among individuals with a new diagnosis of HGSOC.
Participants had a new diagnosis of HGSOC and received reflex BRCA1/2 tumour genetic testing as a component of their care. Eligible individuals were recruited from two oncology centres in Toronto, Canada. One week after disclosure of tumour genetic test results, consenting participants were asked to complete a questionnaire that measured cancer-related distress, dispositional optimism, knowledge of hereditary breast/ovarian cancer, recall of tumour genetic test results, satisfaction, and the psychological impact of receiving tumour genetic test results. The Multidimensional Impact of Cancer Risk Assessment (MICRA) questionnaire was used to measure the psychological impact of tumour genetic testing.
76 individuals completed the study survey; 13 said they did not receive their tumour test results. Of the remaining 63 participants, the average MICRA score was 26.8 (SD = 16.3). Higher total MICRA scores were seen among those with children (p = 0.02), who received treatment with primary surgery (p = 0.02), and had higher reported cancer-related distress (p < 0.001). Higher dispositional optimism (p < 0.001) and increasing age (p = 0.03) were associated with lower total MICRA scores. Most (83.5%) participants reported being satisfied/highly satisfied with having tumour testing completed; however, 40.8% could not accurately recall their tumor test results.
This study is the first to assess psychological outcomes following reflex BRCA1/2 tumour genetic testing in women newly diagnosed with HGSOC. Increased dispositional optimism provided a protective effect, while increased cancer-related distress increased the psychological impact of tumour genetic testing. Educational resources are needed to help increase patient understanding and recall of tumour results, particularly when tumour genetic testing includes analysis of genes that may have implications for hereditary cancer risk. Additional research is required to better understand the patient experience of reflex tumour genetic testing.
We present a well-dated, high-resolution, ~
45
kyr lake sediment record reflecting regional temperature and precipitation change in the continental interior of the Southern Hemisphere (SH) tropics of ...South America. The study site is Laguna La Gaiba (LLG), a large lake (95
km
2) hydrologically-linked to the Pantanal, an immense, seasonally-flooded basin and the world's largest tropical wetland (135,000
km
2). Lake-level changes at LLG are therefore reflective of regional precipitation. We infer past fluctuations in precipitation at this site through changes in: i) pollen-inferred extent of flood-tolerant forest; ii) relative abundance of
terra firme humid tropical forest versus seasonally-dry tropical forest pollen types; and iii) proportions of deep- versus shallow-water diatoms. A probabilistic model, based on plant family and genus climatic optima, was used to generate quantitative estimates of past temperature from the fossil pollen data. Our temperature reconstruction demonstrates rising temperature (by 4
°C) at 19.5
kyr BP, synchronous with the onset of deglacial warming in the central Andes, strengthening the evidence that climatic warming in the SH tropics preceded deglacial warming in the Northern Hemisphere (NH) by at least 5
kyr. We provide unequivocal evidence that the climate at LLG was markedly drier during the last glacial period (45.0–12.2
kyr BP) than during the Holocene, contrasting with SH tropical Andean and Atlantic records that demonstrate a strengthening of the South American summer monsoon during the global Last Glacial Maximum (~
21
kyr BP), in tune with the ~
20
kyr precession orbital cycle. Holocene climate conditions occurred as early as 12.8–12.2
kyr BP, when increased precipitation in the Pantanal catchment caused heightened flooding and rising lake levels in LLG. In contrast to this strong geographic variation in LGM precipitation across the continent, expansion of tropical dry forest between 10 and 3
kyr BP at LLG strengthens the body of evidence for widespread early–mid Holocene drought across tropical South America.
► We reveal Pleistocene–Holocene climate change in lowland tropical South America. ► Early deglacial warming at 19.5
kyr in the lowlands corroborates Andean records. ► Glacial-aged drought contrasts tropical Andean and Atlantic records. ► The onset of a wetter interglacial climate begins at 12.8
kyr BP. ► The changing precipitation regime is paced with global glacial–interglacial cycles.
Seasonal dry tropical forest (STDF) is a widespread vegetation type in western Mexico. Generally, this type of forest develops in semihumid habitats where lacustrine basins are scarce, preventing ...documentation of the vegetation history and forest dynamics using a paleoecological approach. Here, we present a palynological record from the Santa Maria del Oro crater lake, located within the distribution area of the STDF and the adjacent dry oak forest which gives insight into the changes in diversity and human impact at this tropical site. Pollen data, in combination with geochemical analysis and microcharcoal data from a lacustrine sequence, are used to discuss vegetation change and diversity in the plant assemblages related to drought or anthropogenic activity over the last 5000 years. Our results show three distinct periods of drought in the basin, from 4200 to 3850, 3100 to 2300, 1570 to 1100 and 300 cal year BP, with changes in vegetation composition mainly related to a decrease in taxa diversity during these periods. Based on the presence of maize pollen, two periods of human activity (3790–2160 and 280 cal year BP to present) were detected with an increase in herbaceous pollen used as a surrogate for deforestation. These two disturbance periods, pre-Columbian and postcolonial, occurred during wet conditions in the basin. Our results highlight the correlation between El Niño events, drought and fire with changes in the composition and diversity of STDF.
Perceptions of climate change, the impacts of and responses to climatic variability and extreme weather are explored in three communities in the Yucatan Peninsula, Mexico, in relation to livelihood ...resilience. These communities provide examples of the most common livelihood strategies across the region: small-scale fisheries (San Felipe) and semi-subsistence small-holder farming (Tzucacab and Calakmul). Although the perception that annual rainfall is reducing is not supported by instrumental records, changes in the timing of vital summer rainfall and an intensification of the mid-summer drought (
canicula
) are confirmed. The impact of both droughts and hurricanes on livelihoods and crop yields was reported across all communities, although the severity varied. Changes in traditional
milpa
cultivation were seen to be driven by less reliable rainfall but also by changes in Mexico’s agricultural and wider economic policies. Diversification was a common adaptation response across all communities and respondents, resulting in profound changes in livelihood strategies. Government attempts to reduce vulnerability were found to lack continuity, be hard to access and too orientated toward commercial scale producers. Population growth, higher temperatures and reduced summer rainfall will increase the pressures on communities reliant on small-scale farming and fishing, and a more nuanced understanding of both impacts and adaptations is required for improved livelihood resilience. Greater recognition of such local-scale adaptation strategies should underpin the developing Mexican National Adaptation Policy and provide a template for approaches internationally as adaptation becomes an increasingly important part of the global strategy to cope with climate change.
The Lagrangian tropospheric ozone model ELMO-v2 (Edinburgh Lancaster Model for Ozone) is applied to the intense 2003 ozone episode in SE England. When using model parameters representative of typical ...episodes, ELMO-v2 was found to underestimate ozone levels substantially during peak ozone days, but, by increasing three parameters (temperature, biogenic and anthropogenic VOC emission rates) to levels close to those observed, good agreement between modelled and observed ozone was achieved. Using attribution techniques possible with a Lagrangian model, the episode was divided into five phases with each exhibiting different geographical origins for ozone precursor emissions. Anthropogenic VOCs, primarily of European (non-UK) origin, made the biggest contribution to modelled ozone levels. European biogenic VOC emissions significantly contributed to ozone levels on some days, whereas the contribution from UK biogenic VOC emissions was comparatively small throughout. The VOC:NOx ratio was also shown to change during the episode, with high ozone days being less VOC-sensitive. The implications of both variable NOx/VOC sensitivity and the possibility of more frequent heatwaves due to climate change need to be taken into account in planning effective future emissions reductions to control ground-level ozone in the UK.
•ELMO-v2 models ozone levels during the 2003 heatwave at Writtle, UK.•Effects of temperature on chemistry and emissions (AVOCs, BVOCs) considered.•Ratio of ozone attributed to AVOC and BVOC emissions is roughly 3:1.•Source attribution reveals varied geographic origins of ozone.•Future temperature increases may reduce benefits of precursor emission reductions.
The global climate changes that led to the expansion and contraction of high latitude ice sheets during the Quaternary period were associated with equally dramatic changes in tropical environments. ...These included shifts in vegetation zones, changes in the hydrology and ecology of lakes and rivers, and fluctuations in the size of mountain glaciers and sandydeserts. Until recently it was thought that such changes were triggered by fluctuations in the distribution of polar ice cover. Now there is increasing recognition that the tropics themselves have acted as drivers of global climate change over a range of timescales.The aim of Quaternary Environmental Change in the Tropicsis to provide a synthesis of the changes that occurred in tropical terrestrial and marine systems during the Pleistocene and Holocene, complementing data-derived reconstructions with output from state-of-the-art climate models. It is targeted at final-year undergraduate students and research specialists, but will provide an introduction to tropical Quaternary research for a variety of other readers.
Here we review palaeoclimatic records from Mexico which have a reasonable chronological framework and are readily accessible. Reconstructions are based on pollen, diatoms, sediment chemistry and ...isotopes, packrat middens and glacial records and are discussed within the context of Central Mexico, the Yucatan and Northern Mexico, the three regions for which significant information is available. The available data indicate that over the Late Pleistocene and Holocene there have been significant climatic changes in Mexico, although smaller in magnitude than in other parts of the northern hemisphere tropics and subtropics. Maps of conditions at 18,000, 9000, 6000, 5000 and 1000 yr BP are presented. These show that northern Mexico and the Yucatan often show opposite climatic signals, whilst the highlands of central Mexico are more variable. Around the Last Glacial Maximum it seems that the modern summer precipitation regime had collapsed. Northern Mexico, however, was much wetter than today due to increased winter rainfall. Modern rainfall patterns were not fully established until after 9000
yr BP and generally wet conditions prevailed about 6000
yr BP. The mid-Holocene seems to have been a period of great climatic variability with a number of records showing oscillations between 6000 and 5000
yr BP. A period of marked aridity is recorded in the Yucatan and central Mexico about 1000
yr BP. More well-dated, continuous records are needed, especially covering the last glacial–interglacial transition. The changing balance between temperate and tropical climate systems and the influence of the Pacific compared with the Gulf of Mexico/Caribbean warrant further investigation.
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