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Abstract Oxygen isotopes (δ 18O) are the most commonly utilized speleothem proxy and have provided many foundational records of paleoclimate. Thus, understanding processes affecting speleothem δ 18O is crucial. Yet, prior calcite precipitation (PCP), a process driven by local hydrology, is a widely ignored control of speleothem δ 18O. Here we investigate the effects of PCP on a stalagmite δ 18O record from central Vietnam, spanning 45 – 4 ka. We employ a geochemical model that utilizes speleothem Mg/Ca and cave monitoring data to correct the δ 18O record for PCP effects. The resulting record exhibits improved agreement with regional speleothem δ 18O records and climate model simulations, suggesting that the corrected record more accurately reflects precipitation δ 18O (δ 18Op). Without considering PCP, our interpretations of the δ 18O record would have been misleading. To avoid misinterpretations of speleothem δ 18O, our results emphasize the necessity of considering PCP as a significant driver of speleothem δ 18O.

The winter and summer monsoons in Southeast Asia are important but highly variable sources of rainfall. Current understanding of the winter monsoon is limited by conflicting proxy observations, resulting from the decoupling of regional atmospheric circulation patterns and local rainfall dynamics. These signals are difficult to decipher in paleoclimate reconstructions. Here, we present a winter monsoon speleothem record from Southeast Asia covering the Holocene and find that winter and summer rainfall changed synchronously, forced by changes in the Pacific and Indian Oceans. In contrast, regional atmospheric circulation shows an inverse relation between winter and summer controlled by seasonal insolation over the Northern Hemisphere. We show that disentangling the local and regional signal in paleoclimate reconstructions is crucial in understanding and projecting winter and summer monsoon variability in Southeast Asia.

Most paleoclimate studies of Mainland Southeast Asia hydroclimate focus on the summer monsoon, with few studies investigating rainfall in other seasons. Here, we present a multiproxy stalagmite record (45,000 to 4,000 years) from central Vietnam, a region that receives most of its annual rainfall in autumn (September-November). We find evidence of a prolonged dry period spanning the last glacial maximum that is punctuated by an abrupt shift to wetter conditions during the deglaciation at ~14 ka. Paired with climate model simulations, we show that sea-level change drives autumn monsoon rainfall variability on glacial-orbital timescales. Consistent with the dry signal in the stalagmite record, climate model simulations reveal that lower glacial sea level exposes land in the Gulf of Tonkin and along the South China Shelf, reducing convection and moisture delivery to central Vietnam. When sea level rises and these landmasses flood at ~14 ka, moisture delivery to central Vietnam increases, causing an abrupt shift from dry to wet conditions. On millennial timescales, we find signatures of well-known Heinrich Stadials (HS) (dry conditions) and Dansgaard-Oeschger Events (wet conditions). Model simulations show that during the dry HS, changes in sea surface temperature related to meltwater forcing cause the formation of an anomalous anticyclone in the Western Pacific, which advects dry air across central Vietnam, decreasing autumn rainfall. Notably, sea level modulates the magnitude of millennial-scale dry and wet phases by muting dry events and enhancing wet events during periods of low sea level, highlighting the importance of this mechanism to autumn monsoon variability.

Abstract Background To evaluate the effectiveness of delivering feedback reports to increase completion of LST notes among VA Home Based Primary Care (HBPC) teams. The Life Sustaining Treatment Decisions Initiative (LSTDI) was implemented throughout the Veterans Health Administration (VHA) in the United States in 2017 to ensure that seriously ill Veterans have care goals and LST decisions elicited and documented. Methods We distributed monthly feedback reports summarizing LST template completion rates to 13 HBPC intervention sites between October 2018 and February 2020 as the sole implementation strategy. We used principal component analyses to match intervention to 26 comparison sites and used interrupted time series/segmented regression analyses to evaluate the differences in LST template completion rates between intervention and comparison sites. Data were extracted from national databases for VA HBPC in addition to interviews and surveys in a mixed methods process evaluation. Results LST template completion rose from 6.3 to 41.9% across both intervention and comparison HBPC teams between March 1, 2018, and February 26, 2020. There were no statistically significant differences for intervention sites that received feedback reports. Conclusions Feedback reports did not increase documentation of LST preferences for Veterans at intervention compared with comparison sites. Observed increases in completion rates across intervention and comparison sites can likely be attributed to implementation strategies used nationally as part of the national roll-out of the LSTDI. Our results suggest that feedback reports alone were not an effective implementation strategy to augment national implementation strategies in HBPC teams.

Abstract The winter and summer monsoons in Southeast Asia are important but highly variable sources of rainfall. Current understanding of the winter monsoon is limited by conflicting proxy observations, resulting from the decoupling of regional atmospheric circulation patterns and local rainfall dynamics. These signals are difficult to decipher in paleoclimate reconstructions. Here, we present a winter monsoon speleothem record from Southeast Asia covering the Holocene and find that winter and summer rainfall changed synchronously, forced by changes in the Pacific and Indian Oceans. In contrast, regional atmospheric circulation shows an inverse relation between winter and summer controlled by seasonal insolation over the Northern Hemisphere. We show that disentangling the local and regional signal in paleoclimate reconstructions is crucial in understanding and projecting winter and summer monsoon variability in Southeast Asia.

Abstract Background Palliative care is an effective model of care focused on maximizing quality of life and relieving the suffering of people with serious illnesses, including dementia. Evidence shows that many people receiving care in nursing homes are eligible for and would benefit from palliative care services. Yet, palliative care is not consistently available in nursing home settings. There is a need to test pragmatic strategies to implement palliative care programs in nursing homes. Methods/design The UPLIFT-AD (Utilizing Palliative Leaders in Facilities to Transform care for people with Alzheimer’s Disease) study is a pragmatic stepped wedge trial in 16 nursing homes in Maryland and Indiana, testing the effectiveness of the intervention while assessing its implementation. The proposed intervention is a palliative care program, including 1) training at least two facility staff as Palliative Care Leads, 2) training for all staff in general principles of palliative care, 3) structured screening for palliative care needs, and 4) on-site specialty palliative care consultations for a one-year intervention period. All residents with at least moderate cognitive impairment, present in the facility for at least 30 days, and not on hospice at baseline are considered eligible. Opt-out consent is obtained from legal decision-makers. Outcome assessments measuring symptoms and quality of care are obtained from staff and family proxy respondents at four time points: pre-implementation (baseline), six months after implementation, at 12 months (conclusion of implementation), and six months after the end of implementation. Palliative care attitudes and practices are assessed through surveys of frontline nursing home staff both pre- and post-implementation. Qualitative and quantitative implementation data, including fidelity assessments and interviews with Palliative Care Leads, are also collected. The study will follow the Declaration of Helsinki. Discussion This trial assesses the implementation and effectiveness of a robust palliative care intervention for residents with moderate-to-advanced cognitive impairment in 16 diverse nursing homes. The intervention represents an innovative, pragmatic approach that includes both internal capacity-building of frontline nursing home staff, and support from external palliative care specialty consultants. Trial registration The project is registered on ClinicalTrials.gov: NCT04520698.

The interpretation of palaeoclimate archives based on oxygen isotopes depends critically on a detailed understanding of processes controlling the isotopic composition of precipitation. In the summer monsoonal realm, like Southeast Asia, seasonally and interannually depleted oxygen isotope ratios in precipitation have been linked to the summer monsoon strength. However, in some regions, such as central Vietnam, the majority of precipitation falls outside the summer monsoon period. We investigate processes controlling stable isotopes in precipitation from central Vietnam by combining moisture uptake calculations with monthly stable isotope data observed over five years. We find that the isotopic seasonal cycle in this region is driven by a shift in moisture source from the Indian Ocean to the South China Sea. This shift is reflected in oxygen isotope ratios with low values (- 8 to - 10‰) during summer and high values during spring/winter (0 to - 3‰), while 70% of the annual rainfall occurs during autumn. Interannual changes in precipitation isotopes in central Vietnam are governed by the timing of the seasonal onset and withdrawal of the Intertropical Convergence Zone, which controls the amount of vapour contributed from each source.

Between 5 and 4 thousand years ago, crippling megadroughts led to the disruption of ancient civilizations across parts of Africa and Asia, yet the extent of these climate extremes in mainland Southeast Asia (MSEA) has never been defined. This is despite archeological evidence showing a shift in human settlement patterns across the region during this period. We report evidence from stalagmite climate records indicating a major decrease of monsoon rainfall in MSEA during the mid- to late Holocene, coincident with African monsoon failure during the end of the Green Sahara. Through a set of modeling experiments, we show that reduced vegetation and increased dust loads during the Green Sahara termination shifted the Walker circulation eastward and cooled the Indian Ocean, causing a reduction in monsoon rainfall in MSEA. Our results indicate that vegetation-dust climate feedbacks from Sahara drying may have been the catalyst for societal shifts in MSEA via ocean-atmospheric teleconnections.

Here, the authors show that the glycosylceramide synthesis inhibitor and FDA approved drug Eliglustat inhibits autophagic degradation of TRAF3 which is a key step for osteoclast differentiation and thereby improves myeloma bone lesions.

Low-lying coral reef islands have been projected to become uninhabitable by the end of the century due to sea level rise, but such projections of vulnerability assume that reef islands are static landforms that flood incrementally with sea level rise. In fact, GIS-based reef island shoreline analyses have demonstrated that reef islands are highly dynamic landforms that may adjust their shorelines in response to changing environmental conditions. However, the vast majority of reef island shoreline analyses have been undertaken in the Pacific Ocean, leaving our understanding of changes in the Indian Ocean more limited. Further, our knowledge of how island dynamics can impact groundwater resources is restricted due to the assumption that islands will exhibit purely erosional responses to sea level rise. Here, we analyse shoreline evolution on 49 reef islands over a 50-year timeframe in Huvadhoo Atoll, Maldives. Additionally, rates of shoreline change were used to undertake numerical modelling of shifts in freshwater lens volume in 2030, 2050 and 2100 in response to changes in recharge. Despite sea level rising at 4.24 mm/year (1969-2019), accretion was prevalent on 53% of islands, with the remaining islands eroding (25%) or remaining stable (22%). Average net shoreline movement was 4.13 m, ranging from -17.51 to 65.73 m; and the average rate of shoreline change (weighted linear regression) was 0.13 m/year, ranging from -0.07 to 2.65 m/year. The magnitudes and rates of reef island evolution were found to be highly site-specific, with island type found to be the only significant predictor of either net shoreline movement or weighted linear regression. Results suggest that freshwater lens volume was substantially impacted by shoreline change compared to changes in recharge whereby accretion and erosion led to large increases (up to 65.05%) decreases (up to -50.4%) in les volume, respectively. We suggest that the capacity of reef islands to both (1) adjust their shorelines, and even accrete, under conditions of sea level rise; and (2) increase their storage of groundwater over the coming decades represents highly valuable geomorphic ecosystem services.

Abstract Background Empirical evidence supports the use of structured goals of care conversations and documentation of life-sustaining treatment (LST) preferences in durable, accessible, and actionable orders to improve the care for people living with serious illness. As the largest integrated healthcare system in the USA, the Veterans Health Administration (VA) provides an excellent environment to test implementation strategies that promote this evidence-based practice. The Preferences Elicited and Respected for Seriously Ill Veterans through Enhanced Decision-Making (PERSIVED) program seeks to improve care outcomes for seriously ill Veterans by supporting efforts to conduct goals of care conversations, systematically document LST preferences, and ensure timely and accurate communication about preferences across VA and non-VA settings. Methods PERSIVED encompasses two separate but related implementation projects that support the same evidence-based practice. Project 1 will enroll 12 VA Home Based Primary Care (HBPC) programs and Project 2 will enroll six VA Community Nursing Home (CNH) programs. Both projects begin with a pre-implementation phase during which data from diverse stakeholders are gathered to identify barriers and facilitators to adoption of the LST evidence-based practice. This baseline assessment is used to tailor quality improvement activities using audit with feedback and implementation facilitation during the implementation phase. Site champions serve as the lynchpin between the PERSIVED project team and site personnel. PERSIVED teams support site champions through monthly coaching sessions. At the end of implementation, baseline site process maps are updated to reflect new steps and procedures to ensure timely conversations and documentation of treatment preferences. During the sustainability phase, intense engagement with champions ends, at which point champions work independently to maintain and improve processes and outcomes. Ongoing process evaluation, guided by the RE-AIM framework, is used to monitor Reach, Adoption, Implementation, and Maintenance outcomes. Effectiveness will be assessed using several endorsed clinical metrics for seriously ill populations. Discussion The PERSIVED program aims to prevent potentially burdensome LSTs by consistently eliciting and documenting values, goals, and treatment preferences of seriously ill Veterans. Working with clinical operational partners, we will apply our findings to HBPC and CNH programs throughout the national VA healthcare system during a future scale-out period.

CorrectionThe authors would like to correct errors in the original article [1] that may have lead readers to misinterpret the scope, evidence base and target population of VHA Handbook 1004.03 "Life-Sustaining Treatment (LST) Decisions: Eliciting, Documenting, and Honoring Patients' Values, Goals, and Preferences".

Oxygen isotopes (δ18O) are the most commonly utilized speleothem proxy and have provided many foundational records of paleoclimate. Thus, understanding processes affecting speleothem δ18O is crucial. Yet, prior calcite precipitation (PCP), a process driven by local hydrology, is a widely ignored control of speleothem δ18O. Here we investigate the effects of PCP on a stalagmite δ18O record from central Vietnam, spanning 45 – 4 ka. We employ a geochemical model that utilizes speleothem Mg/Ca and cave monitoring data to correct the δ18O record for PCP effects. The resulting record exhibits improved agreement with regional speleothem δ18O records and climate model simulations, suggesting that the corrected record more accurately reflects precipitation δ18O (δ18Op). Without considering PCP, our interpretations of the δ18O record would have been misleading. To avoid misinterpretations of speleothem δ18O, our results emphasize the necessity of considering PCP as a significant driver of speleothem δ18O. This study finds that in-cave processes affect speleothem oxygen isotope records. Correcting for these processes improves agreement with other regional records and climate models, providing a more accurate reflection of past hydroclimate change. [ABSTRACT FROM AUTHOR]

Home-based pediatric palliative and hospice care (PPHC) supports the hundreds of thousands of children with serious illness and complex care needs and their families in the home setting. Considerable variation, however, exists in the provision and quality of home-based PPHC in the U.S. Ensuring equitable, high-quality home-based PPHC for all children requires the evaluation of families' care experiences and assessment of whether these experiences are aligned with their needs and priorities. To evaluate the psychometric properties of the previously developed 23-item home-based PPHC EXPERIENCE Measure for use with families of children receiving home-based PPHC in the United States. Participants included families recruited from the Children's Hospital of Philadelphia, Courageous Parents Network, and several other hospital- and community-based PPHC programs across the U.S. who provide home-based PPHC services. Participants completed the EXPERIENCE Measure at baseline and again at retest. We evaluated the factor structure of the EXPERIENCE Measure, as well as evidence regarding score reliability and validity. Eighty-two family participants completed the baseline and 53 completed the retest questionnaire from 15 states across the U.S. We found evidence for the score reliability and validity of a four-domain EXPERIENCE measure. The EXPERIENCE Measure is a tool with evidence for reliable and valid scores to evaluate family-reported home-based PPHC experiences at the time care is being received. Future work will evaluate the usability (i.e., acceptability, feasibility, and clinical actionability) of EXPERIENCE, including the sensitivity of the instrument to change over time and its impact on real-time clinical actions. [ABSTRACT FROM AUTHOR]

Background: Modeled after the Physician Orders for Life Sustaining Treatment program, the Veterans Health Administration (VA) implemented the Life‐Sustaining Treatment (LST) Decisions Initiative to improve end‐of‐life outcomes by standardizing LST preference documentation for seriously ill Veterans. This study examined the associations between LST documentation and family evaluation of care in the final month of life for Veterans in VA nursing homes. Methods: Retrospective, cross‐sectional analysis of data for decedents in VA nursing homes between July 1, 2018 and January 31, 2020 (N = 14,575). Regression modeling generated odds for key end‐of‐life outcomes and family ratings of care quality. Results: LST preferences were documented for 12,928 (89%) of VA nursing home decedents. Contrary to our hypothesis, neither receipt of wanted medications and medical treatment (adjusted odds ratio [OR]: 0.85, 95% confidence interval [CI] 0.63, 1.16) nor ratings of overall care in the last month of life (adjusted OR: 0.96, 95% CI 0.76, 1.22) differed significantly between those with and without completed LST templates in adjusted analyses. Conclusions: Among Community Living Center (CLC) decedents, 89% had documented LST preferences. No significant differences were observed in family ratings of care between Veterans with and without documentation of LST preferences. Interventions aimed at improving family ratings of end‐of‐life care quality in CLCs should not target LST documentation in isolation of other factors associated with higher family ratings of end‐of‐life care quality. [ABSTRACT FROM AUTHOR]