Amazon forest biogeography predicts resilience and vulnerability to drought.

Amazonia contains the most extensive tropical forests on Earth, but Amazon carbon sinks of atmospheric CO2 are declining, as deforestation and climate-change-associated droughts1-4 threaten to push these forests past a tipping point towards collapse5-8. Forests exhibit complex drought responses, indicating both resilience (photosynthetic greening) and vulnerability (browning and tree mortality), that are difficult to explain by climate variation alone9-17. Here we combine remotely sensed photosynthetic indices with ground-measured tree demography to identify mechanisms underlying drought resilience/vulnerability in different intact forest ecotopes18,19 (defined by water-table depth, soil fertility and texture, and vegetation characteristics). In higher-fertility southern Amazonia, drought response was structured by water-table depth, with resilient greening in shallow-water-table forests (where greater water availability heightened response to excess sunlight), contrasting with vulnerability (browning and excess tree mortality) over deeper water tables. Notably, the resilience of shallow-water-table forest weakened as drought lengthened. By contrast, lower-fertility northern Amazonia, with slower-growing but hardier trees (or, alternatively, tall forests, with deep-rooted water access), supported more-drought-resilient forests independent of water-table depth. This functional biogeography of drought response provides a framework for conservation decisions and improved predictions of heterogeneous forest responses to future climate changes, warning that Amazonia's most productive forests are also at greatest risk, and that longer/more frequent droughts are undermining multiple ecohydrological strategies and capacities for Amazon forest resilience.

The CO2 record at the Amazon Tall Tower Observatory: A new opportunity to study processes on seasonal and inter-annual scales.

High-quality atmospheric CO2  measurements are sparse in Amazonia, but can provide critical insights into the spatial and temporal variability of sources and sinks of CO2 . In this study, we present the first 6 years (2014-2019) of continuous, high-precision measurements of atmospheric CO2 at the Amazon Tall Tower Observatory (ATTO, 2.1°S, 58.9°W). After subtracting the simulated background concentrations from our observational record, we define a CO2 regional signal ( ΔCO2obs ) that has a marked seasonal cycle with an amplitude of about 4 ppm. At both seasonal and inter-annual scales, we find differences in phase between ΔCO2obs and the local eddy covariance net ecosystem exchange (EC-NEE), which is interpreted as an indicator of a decoupling between local and non-local drivers of ΔCO2obs . In addition, we present how the 2015-2016 El Niño-induced drought was captured by our atmospheric record as a positive 2σ anomaly in both the wet and dry season of 2016. Furthermore, we analyzed the observed seasonal cycle and inter-annual variability of ΔCO2obs together with net ecosystem exchange (NEE) using a suite of modeled flux products representing biospheric and aquatic CO2 exchange. We use both non-optimized and optimized (i.e., resulting from atmospheric inverse modeling) NEE fluxes as input in an atmospheric transport model (STILT). The observed shape and amplitude of the seasonal cycle was captured neither by the simulations using the optimized fluxes nor by those using the diagnostic Vegetation and Photosynthesis Respiration Model (VPRM). We show that including the contribution of CO2 from river evasion improves the simulated shape (not the magnitude) of the seasonal cycle when using a data-driven non-optimized NEE product (FLUXCOM). The simulated contribution from river evasion was found to be 25% of the seasonal cycle amplitude. Our study demonstrates the importance of the ATTO record to better understand the Amazon carbon cycle at various spatial and temporal scales.

Biological processes dominate seasonality of remotely sensed canopy greenness in an Amazon evergreen forest.

Satellite observations of Amazon forests show seasonal and interannual variations, but the underlying biological processes remain debated. Here we combined radiative transfer models (RTMs) with field observations of Amazon forest leaf and canopy characteristics to test three hypotheses for satellite-observed canopy reflectance seasonality: seasonal changes in leaf area index, in canopy-surface leafless crown fraction and/or in leaf demography. Canopy RTMs (PROSAIL and FLiES), driven by these three factors combined, simulated satellite-observed seasonal patterns well, explaining c. 70% of the variability in a key reflectance-based vegetation index (MAIAC EVI, which removes artifacts that would otherwise arise from clouds/aerosols and sun-sensor geometry). Leaf area index, leafless crown fraction and leaf demography independently accounted for 1, 33 and 66% of FLiES-simulated EVI seasonality, respectively. These factors also strongly influenced modeled near-infrared (NIR) reflectance, explaining why both modeled and observed EVI, which is especially sensitive to NIR, captures canopy seasonal dynamics well. Our improved analysis of canopy-scale biophysics rules out satellite artifacts as significant causes of satellite-observed seasonal patterns at this site, implying that aggregated phenology explains the larger scale remotely observed patterns. This work significantly reconciles current controversies about satellite-detected Amazon phenology, and improves our use of satellite observations to study climate-phenology relationships in the tropics.

Causes of reduced leaf-level photosynthesis during strong El Niño drought in a Central Amazon forest.

Sustained drought and concomitant high temperature may reduce photosynthesis and cause tree mortality. Possible causes of reduced photosynthesis include stomatal closure and biochemical inhibition, but their relative roles are unknown in Amazon trees during strong drought events. We assessed the effects of the recent (2015) strong El Niño drought on leaf-level photosynthesis of Central Amazon trees via these two mechanisms. Through four seasons of 2015, we measured leaf gas exchange, chlorophyll a fluorescence parameters, chlorophyll concentration, and nutrient content in leaves of 57 upper canopy and understory trees of a lowland terra firme forest on well-drained infertile oxisol. Photosynthesis decreased 28% in the upper canopy and 17% in understory trees during the extreme dry season of 2015, relative to other 2015 seasons and was also lower than the climatically normal dry season of the following non-El Niño year. Photosynthesis reduction under extreme drought and high temperature in the 2015 dry season was related only to stomatal closure in both upper canopy and understory trees, and not to chlorophyll a fluorescence parameters, chlorophyll, or leaf nutrient concentration. The distinction is important because stomatal closure is a transient regulatory response that can reverse when water becomes available, whereas the other responses reflect more permanent changes or damage to the photosynthetic apparatus. Photosynthesis decrease due to stomatal closure during the 2015 extreme dry season was followed 2 months later by an increase in photosynthesis as rains returned, indicating a margin of resilience to one-off extreme climatic events in Amazonian forests.

Religious Involvement and Telomere Length in Women Family Caregivers.

Telomere length (TL) is an indicator of cellular aging associated with longevity and psychosocial stress. We examine here the relationship between religious involvement and TL in 251 stressed female family caregivers recruited into a 2-site study. Religious involvement, perceived stress, caregiver burden, depressive symptoms, and social support were measured and correlated with TL in whole blood leukocytes. Results indicated a U-shaped relationship between religiosity and TL. Those scoring in the lowest 10% on religiosity tended to have the longest telomeres (5743 bp ± 367 vs. 5595 ± 383, p = 0.069). However, among the 90% of caregivers who were at least somewhat religious, religiosity was significantly and positively related to TL after controlling for covariates (B = 1.74, SE = 0.82, p = 0.034). Whereas nonreligious caregivers have relatively long telomeres, we found a positive relationship between religiosity and TL among those who are at least somewhat religious.

Effects of religious vs. standard cognitive behavioral therapy on therapeutic alliance: A randomized clinical trial.

BACKGROUND: Treatments that integrate religious clients' beliefs into therapy may enhance the therapeutic alliance (TA) in religious clients. OBJECTIVE: Compare the effects of religiously integrated cognitive behavioral therapy (RCBT) and standard CBT (SCBT) on TA in adults with major depression and chronic medical illness. METHOD: Multi-site randomized controlled trial in 132 participants, of whom 108 (SCBT = 53, RCBT = 55) completed the Revised Helping Alliance Questionnaire (HAQ-II) at 4, 8, and 12 weeks. Trajectory of change in scores over time was compared between groups. RESULTS: HAQ-II score at 4 weeks predicted a decline in depressive symptoms over time independent of treatment group (B = -0.06, SE = 0.02, p = 0.002, n = 108). There was a marginally significant difference in HAQ-II scores at 4 weeks that favored RCBT (p = 0.076); however, the mixed effects model indicated a significant group by time interaction that favored the SCBT group (B = 1.84, SE = 0.90, degrees of freedom = 181, t = 2.04, p = 0.043, d = 0.30). CONCLUSIONS: While RCBT produces a marginally greater improvement in TA initially compared with SCBT, SCBT soon catches up.

Effects on Daily Spiritual Experiences of Religious Versus Conventional Cognitive Behavioral Therapy for Depression.

We compared religiously integrated cognitive behavioral therapy (RCBT) versus conventional CBT (CCBT) on increasing daily spiritual experiences (DSE) in major depressive disorder and chronic medical illness. A total of 132 participants aged 18-85 were randomized to either RCBT (n = 65) or CCBT (n = 67). Participants received ten 50-min sessions (primarily by telephone) over 12 weeks. DSE was assessed using the Daily Spiritual Experiences Scale (DSES). Mixed-effects growth curve models compared the effects of treatment group on trajectory of change in DSE. Baseline DSE and changes in DSE were examined as predictors of change in depressive symptoms. DSE increased significantly in both groups. RCBT tended to be more effective than CCBT with regard to increasing DSE (group by time interaction B = -1.80, SE = 1.32, t = -1.36, p = 0.18), especially in those with low religiosity (B = -4.26, SE = 2.27, t = -1.88, p = 0.07). Higher baseline DSE predicted a decrease in depressive symptoms (B = -0.09, SE = 0.04, t = -2.25, p = 0.025), independent of treatment group, and an increase in DSE with treatment correlated with a decrease in depressive symptoms (r = 0.29, p = 0.004). RCBT tends to be more effective than CCBT in increasing DSE, especially in persons with low religiosity. Higher baseline DSE and increases in DSE over time predict a faster resolution of depressive symptoms. Efforts to increase DSE, assessed by a measure such as the DSES, may help with the treatment of depression in the medically ill.

EFFECTS OF RELIGIOUS VERSUS STANDARD COGNITIVE-BEHAVIORAL THERAPY ON OPTIMISM IN PERSONS WITH MAJOR DEPRESSION AND CHRONIC MEDICAL ILLNESS.

BACKGROUND: We compared the effectiveness of religiously integrated cognitive behavioral therapy (RCBT) versus standard CBT (SCBT) on increasing optimism in persons with major depressive disorder (MDD) and chronic medical illness. METHODS: Participants aged 18-85 were randomized to either RCBT (n = 65) or SCBT (n = 67) to receive ten 50-min sessions remotely (94% by telephone) over 12 weeks. Optimism was assessed at baseline, 12 and 24 weeks by the Life Orientation Test-Revised. Religiosity was assessed at baseline using a 29-item scale composed of religious importance, individual religious practices, intrinsic religiosity, and daily spiritual experiences. Mixed effects growth curve models were used to compare the effects of treatment group on trajectory of change in optimism. RESULTS: In the intention-to-treat analysis, both RCBT and SCBT increased optimism over time, although there was no significant difference between treatment groups (B = -0.75, SE = 0.57, t = -1.33, P = .185). Analyses in the highly religious and in the per protocol analysis indicated similar results. Higher baseline religiosity predicted an increase in optimism over time (B = 0.07, SE = 0.02, t = 4.12, P < .0001), and higher baseline optimism predicted a faster decline in depressive symptoms over time (B = -0.61, SE = 0.10, t = -6.30, P < .0001), both independent of treatment group. CONCLUSIONS: RCBT and SCBT are equally effective in increasing optimism in persons with MDD and chronic medical illness. While baseline religiosity does not moderate this effect, religiosity predicts increases in optimism over time independent of treatment group.

Religious vs. conventional cognitive behavioral therapy for major depression in persons with chronic medical illness: a pilot randomized trial.

We examine the efficacy of conventional cognitive behavioral therapy (CCBT) versus religiously integrated CBT (RCBT) in persons with major depression and chronic medical illness. Participants were randomized to either CCBT (n = 67) or RCBT (n = 65). The intervention in both groups consisted of ten 50-minute sessions delivered remotely during 12 weeks (94% by telephone). Adherence to treatment was similar, except in more religious participants in whom adherence to RCBT was slightly greater (85.7% vs. 65.9%, p = 0.10). The intention-to-treat analysis at 12 weeks indicated no significant difference in outcome between the two groups (B = 0.33; SE, 1.80; p = 0.86). Response rates and remission rates were also similar. Overall religiosity interacted with treatment group (B = -0.10; SE, 0.05; p = 0.048), suggesting that RCBT was slightly more efficacious in the more religious participants. These preliminary findings suggest that CCBT and RCBT are equivalent treatments of major depression in persons with chronic medical illness. Efficacy, as well as adherence, may be affected by client religiosity.

Tree Regeneration Under Different Land-Use Mosaics in the Brazilian Amazon's "Arc of Deforestation".

We studied the tree-regeneration patterns in three distinct agricultural settlements in the Eastern Amazon to test the influence of land-use mosaics. The following questions are addressed: are the floristic structure and composition of regenerating trees affected by the various land-use types applied in the agricultural settlements? Do tree-regeneration patterns respond similarly to distinct land-use mosaics? Is there a relationship between tree regeneration and soil characteristics among the land-use types? The regeneration was inventoried at 45 sampling points in each settlement. At each sampling point, fourteen soil variables were analyzed. Nine different land-use types were considered. The floristic structure and composition of the settlements showed differences in the density of individuals and species and high species heterogeneity among the land-use types. The maximum Jaccard similarity coefficient found between land-use types was only 29%. Shade-tolerant species were the most diverse functional group in most land-use types, including pasture and annual crops, ranging from 91% of the number of species in the conserved and exploited forests of Travessão 338-S to 53% in the invaded pastures of Maçaranduba. The land-use types influenced significantly the floristic structure and composition of regenerating trees in two agricultural settlements, but not in third the settlement, which had greater forest cover. This finding demonstrates that the composition of each land-use mosaic, established by different management approaches, affects regeneration patterns. Tree regeneration was related to soil characteristics in all mosaics. Preparation of the area by burning was most likely the determining factor in the differences in soil characteristics between forests and agricultural areas.

Improved allometric models to estimate the aboveground biomass of tropical trees.

Terrestrial carbon stock mapping is important for the successful implementation of climate change mitigation policies. Its accuracy depends on the availability of reliable allometric models to infer oven-dry aboveground biomass of trees from census data. The degree of uncertainty associated with previously published pantropical aboveground biomass allometries is large. We analyzed a global database of directly harvested trees at 58 sites, spanning a wide range of climatic conditions and vegetation types (4004 trees ≥ 5 cm trunk diameter). When trunk diameter, total tree height, and wood specific gravity were included in the aboveground biomass model as covariates, a single model was found to hold across tropical vegetation types, with no detectable effect of region or environmental factors. The mean percent bias and variance of this model was only slightly higher than that of locally fitted models. Wood specific gravity was an important predictor of aboveground biomass, especially when including a much broader range of vegetation types than previous studies. The generic tree diameter-height relationship depended linearly on a bioclimatic stress variable E, which compounds indices of temperature variability, precipitation variability, and drought intensity. For cases in which total tree height is unavailable for aboveground biomass estimation, a pantropical model incorporating wood density, trunk diameter, and the variable E outperformed previously published models without height. However, to minimize bias, the development of locally derived diameter-height relationships is advised whenever possible. Both new allometric models should contribute to improve the accuracy of biomass assessment protocols in tropical vegetation types, and to advancing our understanding of architectural and evolutionary constraints on woody plant development.

Forest fragmentation impacts the seasonality of Amazonian evergreen canopies.

Predictions of the magnitude and timing of leaf phenology in Amazonian forests remain highly controversial. Here, we use terrestrial LiDAR surveys every two weeks spanning wet and dry seasons in Central Amazonia to show that plant phenology varies strongly across vertical strata in old-growth forests, but is sensitive to disturbances arising from forest fragmentation. In combination with continuous microclimate measurements, we find that when maximum daily temperatures reached 35 °C in the latter part of the dry season, the upper canopy of large trees in undisturbed forests lost plant material. In contrast, the understory greened up with increased light availability driven by the upper canopy loss, alongside increases in solar radiation, even during periods of drier soil and atmospheric conditions. However, persistently high temperatures in forest edges exacerbated the upper canopy losses of large trees throughout the dry season, whereas the understory in these light-rich environments was less dependent on the altered upper canopy structure. Our findings reveal a strong influence of edge effects on phenological controls in wet forests of Central Amazonia.

Spatial and temporal fluctuations in COVID-19 fatality rates in Brazilian hospitals.

The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) Gamma variant of concern has spread rapidly across Brazil since late 2020, causing substantial infection and death waves. Here we used individual-level patient records after hospitalization with suspected or confirmed coronavirus disease 2019 (COVID-19) between 20 January 2020 and 26 July 2021 to document temporary, sweeping shocks in hospital fatality rates that followed the spread of Gamma across 14 state capitals, during which typically more than half of hospitalized patients aged 70 years and older died. We show that such extensive shocks in COVID-19 in-hospital fatality rates also existed before the detection of Gamma. Using a Bayesian fatality rate model, we found that the geographic and temporal fluctuations in Brazil's COVID-19 in-hospital fatality rates were primarily associated with geographic inequities and shortages in healthcare capacity. We estimate that approximately half of the COVID-19 deaths in hospitals in the 14 cities could have been avoided without pre-pandemic geographic inequities and without pandemic healthcare pressure. Our results suggest that investments in healthcare resources, healthcare optimization and pandemic preparedness are critical to minimize population-wide mortality and morbidity caused by highly transmissible and deadly pathogens such as SARS-CoV-2, especially in low- and middle-income countries.

Behavioral health interventions being implemented in a VA primary care system.

The integration of behavioral health and primary care has received much attention in the literature. Behavioral health providers (BHPs) in integrated settings are faced with different treatment constraints than those who work in specialty mental health. The existing literature focuses on what BHPs should do in primary care settings; however, little research exists specifying what BHPs are actually doing. This study provides a glimpse into what types of interventions BHPs are using, and what types of patients they are seeing, in primary care. A chart review was conducted of patients (N = 180) seen by BHPs in five Veterans Affairs primary care clinics. Depression was the most common diagnosis, while less common presenting problems included substance abuse/dependence, psychosis, and bipolar disorder. Common interventions used were medical management, psycho-education, elements of cognitive-behavioral therapy (CBT), and supportive psychotherapy. Future research should examine the efficacy of brief interventions in primary care settings.

Report 46: Factors driving extensive spatial and temporal fluctuations in COVID-19 fatality rates in Brazilian hospitals.

The SARS-CoV-2 Gamma variant spread rapidly across Brazil, causing substantial infection and death waves. We use individual-level patient records following hospitalisation with suspected or confirmed COVID-19 to document the extensive shocks in hospital fatality rates that followed Gamma's spread across 14 state capitals, and in which more than half of hospitalised patients died over sustained time periods. We show that extensive fluctuations in COVID-19 in-hospital fatality rates also existed prior to Gamma's detection, and were largely transient after Gamma's detection, subsiding with hospital demand. Using a Bayesian fatality rate model, we find that the geographic and temporal fluctuations in Brazil's COVID-19 in-hospital fatality rates are primarily associated with geographic inequities and shortages in healthcare capacity. We project that approximately half of Brazil's COVID-19 deaths in hospitals could have been avoided without pre-pandemic geographic inequities and without pandemic healthcare pressure. Our results suggest that investments in healthcare resources, healthcare optimization, and pandemic preparedness are critical to minimize population wide mortality and morbidity caused by highly transmissible and deadly pathogens such as SARS-CoV-2, especially in low- and middle-income countries. NOTE: The following manuscript has appeared as 'Report 46 - Factors driving extensive spatial and temporal fluctuations in COVID-19 fatality rates in Brazilian hospitals' at https://spiral.imperial.ac.uk:8443/handle/10044/1/91875 . ONE SENTENCE SUMMARY: COVID-19 in-hospital fatality rates fluctuate dramatically in Brazil, and these fluctuations are primarily associated with geographic inequities and shortages in healthcare capacity.

Genomics and epidemiology of the P.1 SARS-CoV-2 lineage in Manaus, Brazil.

Cases of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection in Manaus, Brazil, resurged in late 2020 despite previously high levels of infection. Genome sequencing of viruses sampled in Manaus between November 2020 and January 2021 revealed the emergence and circulation of a novel SARS-CoV-2 variant of concern. Lineage P.1 acquired 17 mutations, including a trio in the spike protein (K417T, E484K, and N501Y) associated with increased binding to the human ACE2 (angiotensin-converting enzyme 2) receptor. Molecular clock analysis shows that P.1 emergence occurred around mid-November 2020 and was preceded by a period of faster molecular evolution. Using a two-category dynamical model that integrates genomic and mortality data, we estimate that P.1 may be 1.7- to 2.4-fold more transmissible and that previous (non-P.1) infection provides 54 to 79% of the protection against infection with P.1 that it provides against non-P.1 lineages. Enhanced global genomic surveillance of variants of concern, which may exhibit increased transmissibility and/or immune evasion, is critical to accelerate pandemic responsiveness.

Genomics and epidemiology of a novel SARS-CoV-2 lineage in Manaus, Brazil.

Cases of SARS-CoV-2 infection in Manaus, Brazil, resurged in late 2020, despite high levels of previous infection there. Through genome sequencing of viruses sampled in Manaus between November 2020 and January 2021, we identified the emergence and circulation of a novel SARS-CoV-2 variant of concern, lineage P.1, that acquired 17 mutations, including a trio in the spike protein (K417T, E484K and N501Y) associated with increased binding to the human ACE2 receptor. Molecular clock analysis shows that P.1 emergence occurred around early November 2020 and was preceded by a period of faster molecular evolution. Using a two-category dynamical model that integrates genomic and mortality data, we estimate that P.1 may be 1.4-2.2 times more transmissible and 25-61% more likely to evade protective immunity elicited by previous infection with non-P.1 lineages. Enhanced global genomic surveillance of variants of concern, which may exhibit increased transmissibility and/or immune evasion, is critical to accelerate pandemic responsiveness.

Pegylated interferon alpha-associated optic neuropathy.

A 52-year-old man with chronic hepatitis C presented with painless, bilateral, simultaneous nonarteritic anterior ischemic optic neuropathy (NAION) and peripheral neuropathy. Symptoms began 19 weeks after starting peginterferon alpha-2a. The peripheral neuropathy and vision of the right eye improved, but the vision of the left eye worsened after stopping interferon. We identified 23 additional cases of NAION during interferon alpha therapy. At least 12 of these patients suffered bilateral NAION. Patients lost vision 1-40 weeks after initiating therapy. Of 21 eyes that had documented initial and follow-up acuities, 8 improved, 1 worsened, and the rest remained stable. One patient had a painful peripheral neuropathy. Treatment with interferon alpha may result in NAION. Discontinuation of therapy deserves consideration after weighing individual risks and benefits.

The description and evaluation of the implementation of an integrated healthcare model.

Two studies were conducted to examine the practical implementation of an integrated health care model in five primary care clinics in the Upstate New York Veterans Affairs (VA) system. The aims of the studies were: (a) to describe the basic clinical elements of the integrated health care service offered by behavioral health providers (BHPs) in the primary care setting, and (b) to evaluate the perceptions of providers and patients regarding integrated health care practices in their primary care clinics. In Study 1, we reviewed 180 electronic medical records of patients who met with a BHP in primary care. In Study 2, we used semistructured interviews and self-report questionnaires to collect information from 46 primary care providers, 12 BHPs, and 140 patients regarding their perceptions of integrated health care in their primary care clinics. Both studies illustrate a useful method for evaluating the practical implementation of integrated health care models.

Clinical validation and calibration of in vitro peroxide tooth whitening.

OBJECTIVE: The purpose of this study was to validate and calibrate an in vitro test method for screening the performance of peroxide-containing toothpastes against actual clinical whitening performance. An additional objective was to estimate the whitening performance of a new peroxide-additive gel using the in vitro methodology. METHODS: A one-month longitudinal clinical study was performed to provide a benchmark for the in vivo intrinsic whitening performance of a peroxide-containing fluoride toothpaste. An in vitro study was then conducted, using freshly prepared slurries of the same peroxide-containing toothpaste in artificial saliva, to repeatedly treat extracted human teeth with natural intrinsic stain. The effect of cumulative treatment time on whiteness was determined using objective chromometer whiteness measurements (L*, a*, and b*), and more subjective Vita Shade guide (Vitapan) comparisons, and the results were correlated. A non-peroxide fluoride toothpaste was used as a negative control. The peroxide gel additive, combined in a 1:1 ratio with each of two non-peroxide toothpastes and diluted in artificial saliva, was evaluated using the same instrumental and subjective measures for in vitro whitening efficacy. The previously evaluated peroxide toothpaste and one of the non-peroxide toothpastes were used as positive and negative controls, respectively. RESULTS: In the clinical study, the peroxide-containing toothpaste produced a linear increase in tooth whiteness with time, achieving an approximately two Vita Shade guide improvement in whiteness at the end of four weeks. The same peroxide toothpaste in vitro produced a curvilinear increase in tooth whiteness versus cumulative treatment time, with a two-shade increase being achieved in 116 minutes. The non-peroxide control toothpaste produced less than half a shade guide increase in whiteness within the first 30 minutes, and none thereafter. Both the clinical and in vitro studies indicated that further whitening can be obtained with longer use of the peroxide-containing toothpaste or peroxide-additive gel. CONCLUSION: Treatment of naturally stained teeth in vitro with the peroxide toothpaste for 116 cumulative minutes produced the same two-shade increase in whiteness as obtained with twice-daily brushing for four weeks in vivo. The peroxide-additive gel, combined with a non-peroxide toothpaste, is projected to provide a similar two-shade increase in whiteness when used twice daily for four weeks. There are indications that greater intrinsic whiteness increase would be achieved with the peroxide toothpaste or with the peroxide-additive gel plus non-peroxide toothpaste with more extended regular twice-daily use in vivo.