It is currently not well known how coherent carbon and oxygen isotope chronologies from different species and sites are under temperate climate conditions. Here we investigated nine chronologies from ...Switzerland covering the last two centuries, including three deciduous species (Fagus sylvatica, Fraxinus excelsior, and Quercus petraea) and three conifer species (Abies alba, Picea abies, and Pinus sylvestris) from sites neither strongly limited by temperature nor precipitation. All of the chronologies except Fraxinus were significantly correlated to at least one other chronology. Correlations between different species of the same site were of similar strength to correlations between the sites. We observed a strong common high‐frequency (interannual) signal for the δ13C chronologies, whereas the low‐frequency (decadal‐scale) signal was more similar among the δ18O chronologies. For both carbon and oxygen isotopes, we found significant positive relationships with annual and growing season temperatures and negative relationships with precipitation, again of similar magnitude for all species except for Fraxinus, which contained only minor climatic information. Averaging of all chronologies resulted in an increase in the climatic signal of the mean chronology. The combined δ18O record reflected decadal‐scale temperature variations remarkably well (r = 0.72). However, the relationship between climate and carbon isotopes declined over the last 3 decades of the 20th century, probably related to the steep increase in atmospheric CO2 concentrations, resulting in strongly diverging δ13C trends of the different chronologies. Our study indicates that combining chronologies from different species enhances the potential of isotope studies for extending climate reconstructions into areas of temperate climate.
Introduction
The aim of this study was to evaluate white spot lesion (WSL) remineralization and fluoride uptake by the application of fluoride varnishes directly onto artificial WSLs in vitro.
...Methods
MI varnish containing casein phosphopeptide–amorphous calcium phosphate (CPP‐ACP) and 2.26% fluoride and Duraphat varnish containing 2.26% fluoride (no added calcium) were compared with a placebo varnish (no added calcium or fluoride). Two WSLs were prepared in enamel slabs and varnish applied to cover one of the two lesions. Each slab was immersed in artificial saliva for 14 days at 37°C. Mineral content was determined using transverse microradiography and fluoride uptake using electron probe microanalysis. The data were statistically analysed using a linear mixed model.
Results
Both MI and Duraphat varnishes significantly remineralized the covered and uncovered WSLs when compared with the placebo varnish (P < 0.001). The WSLs covered with varnish showed greater remineralization than those uncovered. MI varnish produced the highest level of remineralization and significantly greater fluoride uptake (0.44 ± 0.08 wt%) compared with Duraphat (0.24 ± 0.03 wt%) and the placebo varnish (0.06 ± 0.05 wt%).
Conclusion
Varnish containing fluoride and CPP‐ACP was superior to varnish containing fluoride alone in promoting WSL remineralization and fluoride uptake.
Synchronised reproduction offers clear benefits to planktonic foraminifera – an important group of marine calcifiers – as it increases the chances of successful gamete fusion. Such synchrony requires ...tuning to an internal or external clock. Evidence exists for lunar reproductive cycles in some species, but its recognition in shell flux time series has proven difficult, raising questions about reproductive strategies. Using spectral analysis of a 4-year time series (mostly at weekly resolution) from the northern Gulf of Mexico, we show that the shell flux of Globorotalia menardii, Globigerinella siphonifera, Orbulina universa, Globigerinoides sacculifer, Globigerinoides ruber (both pink and white varieties), Pulleniatina obliquiloculata, Neogloboquadrina dutertrei, Globigerinella calida and Globigerinita glutinata is characterised by lunar periodicity. However, the lunar rhythm is not present in all size fractions of each species and tends to be more dominant in the flux of larger shells, consistent with reproduction being more prevalent in larger specimens. Lunar periodicity is superimposed on longer term/seasonal changes in the shell fluxes, but accounts for a significant part of the variance in the fluxes. The amplitude of the lunar cycle increases roughly proportional with the magnitude of the flux, demonstrating that most of the population is indeed affected by lunar-phased synchronisation. In most species peak fluxes occur predominantly around, or just after, full moon. Only G. siphonifera and G. calida show a contrasting pattern with peaks concentrated around new moon. Although the exact cause of the synchronisation remains elusive, our data considerably increase the number of species for which lunar synchronised reproduction is reported and suggest that such reproductive behaviour is common in many species of planktonic foraminifera.
Aim
To evaluate the diagnostic and prognostic performance of alternative diagnostic strategies to oral glucose tolerance tests, including random plasma glucose, fasting plasma glucose and HbA1c, ...during the COVID‐19 pandemic.
Methods
Retrospective service data (Cambridge, UK; 17 736 consecutive singleton pregnancies, 2004–2008; 826 consecutive gestational diabetes pregnancies, 2014–2019) and 361 women with ≥1 gestational diabetes risk factor (OPHELIA prospective observational study, UK) were included. Pregnancy outcomes included gestational diabetes (National Institute of Health and Clinical Excellence or International Association of Diabetes and Pregnancy Study Groups criteria), diabetes in pregnancy (WHO criteria), Caesarean section, large‐for‐gestational age infant, neonatal hypoglycaemia and neonatal intensive care unit admission. Receiver‐operating characteristic curves and unadjusted logistic regression were used to compare random plasma glucose, fasting plasma glucose and HbA1c performance.
Results
Gestational diabetes diagnosis was significantly associated with random plasma glucose at 12 weeks area under the receiver‐operating characteristic curve for both criteria 0.81 (95% CI 0.79–0.83), fasting plasma glucose National Institute of Health and Clinical Excellence: area under the receiver‐operating characteristic curve 0.75 (95% CI 0.65–0.85); International Association of Diabetes and Pregnancy Study Groups: area under the receiver‐operating characteristic curve 0.92 (95% CI 0.85–0.98) and HbA1c at 28 weeks' gestation National Institute of Health and Clinical Excellence: 0.83 (95% CI 0.75–0.90); International Association of Diabetes and Pregnancy Study Groups: 0.84 (95% CI 0.77–0.91). Each measure predicts some, but not all, pregnancy outcomes studied. At 12 weeks, ~5% of women would be identified using random plasma glucose ≥8.5 mmol/l (sensitivity 42%; specificity 96%) and at 28 weeks using HbA1c ≥39 mmol/mol (sensitivity 26%; specificity 96%) or fasting plasma glucose ≥5.2–5.4 mmol/l (sensitivity 18–41%; specificity 97–98%).
Conclusions
Random plasma glucose at 12 weeks, and fasting plasma glucose or HbA1c at 28 weeks identify women with hyperglycaemia at risk of suboptimal pregnancy outcomes. These opportunistic laboratory tests perform adequately for risk stratification when oral glucose tolerance testing is not available.
Objectives
To compare biofilm‐forming ability, hydrolytic enzymes and ethanol‐derived acetaldehyde production of oral Candida isolated from the patients with oral cancer and matched non‐oral cancer.
...Material and Methods
Fungal biofilms were grown in RPMI‐1640 medium, and biofilm mass and biofilm activity were assessed using crystal violet staining and XTT salt reduction assays, respectively. Phospholipase, proteinase, and esterase production were measured using agar plate method, while fungal acetaldehyde production was assessed via gas chromatography.
Results
Candida isolated from patients with oral cancer demonstrated significantly higher biofilm mass (P = 0.031), biofilm metabolic activity (P < 0.001), phospholipase (P = 0.002), and proteinase (P = 0.0159) activity than isolates from patients with non‐oral cancer. High ethanol‐derived acetaldehyde‐producing Candida were more prevalent in patients with oral cancer than non‐oral cancer (P = 0.01). In univariate regression analysis, high biofilm mass (P = 0.03) and biofilm metabolic activity (P < 0.001), high phospholipase (P = 0.003), and acetaldehyde production ability (0.01) were significant risk factors for oral cancer; while in the multivariate regression analysis, high biofilm activity (0.01) and phospholipase (P = 0.01) were significantly positive influencing factors on oral cancer.
Conclusion
These data suggest a significant positive association between the ability of Candida isolates to form biofilms, to produce hydrolytic enzymes, and to metabolize alcohol to acetaldehyde with their ability to promote oral cancer development.
Summary
Background
Treatment modifications, including dose escalations, dose reductions, switches, discontinuations and restarts of biologics may be necessary in the management of psoriasis but the ...patterns of usage are incompletely defined.
Objectives
To examine the treatment utilization patterns of adalimumab, etanercept and ustekinumab among biologic‐naïve and non‐naïve patients with psoriasis enrolled in the British Association of Dermatologists Biologic Interventions Register (BADBIR).
Methods
The study cohort included adults with chronic plaque psoriasis who were followed up for ≥ 12 months. Treatment modifications were assessed during the first year of therapy. The time–trend method, comparing the cumulative dose (CD) patients received with the recommended cumulative dose (RCD), was used to assess dosing patterns. Concomitant use of other systemic treatments was also examined.
Results
In total, 2980 patients (adalimumab: 1675; etanercept: 996; ustekinumab: 309) were included; 79·2% were biologic‐naïve. Over 12 months, 77·4% of patients continued the biologic, 2·6% restarted therapy after a break of ≥ 90 days, 2·5% discontinued, and 17·5% switched biologic therapy. Most patients (85·7%) received the RCD of the biologic, although 8·1% were exposed to a higher CD. In total, 749 (25·1%) patients used conventional systemic therapies concomitantly with a biologic at some stage; methotrexate was used most commonly (458; 61·2%). Of those using combination therapy, 454 (60·6%) continued the use of the conventional systemic therapy for > 120 days after the start of the biologic.
Conclusions
More than one‐third of patients experienced treatment modifications within the first year of initiating a biologic. Conventional systemic therapies, particularly methotrexate, were commonly used concurrently, which should be considered when evaluating treatment response and adverse events to biologics in real‐world observational studies.
What's already known about this topic?
Published evidence concerning the utilization patterns of biologic therapies for psoriasis, including dosing, switching, discontinuation and restarts is limited to biologic‐naïve patients.
Furthermore, the ability to determine the patterns of concomitant use of conventional systemic therapies with biologic therapies is confined to a few small‐scale studies.
What does this study add?
Based on a cohort of 2980 patients receiving biologic therapies for psoriasis, 33·7% of patients experienced treatment modifications during their first year of treatment.
There were no significant differences between biologic‐naïve and non‐naïve patients in the proportions of patients who switched, discontinued or restarted therapy.
Conventional systemic therapies, particularly methotrexate, were commonly used concurrently with biologics.
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Climate reconstructions based on stable isotopes in tree rings commonly rely on the assumption that climate‐isotope relations are stable over time. However, studies of tree ring growth have revealed ...trends thought to result from either physiological changes or changes in the climate‐growth relationship. We investigated whether or not similar trends exist for tree ring stable isotopic ratios using a statistical approach. Correlations between climate (temperature and precipitation amount) and tree ring cellulose δ13C and δ18O of oak and pine from Ticino, Switzerland, were calculated for the period AD 1660–2000. Climate calibration of tree rings was enabled by long‐term monthly resolved temperature and precipitation data sets on the basis of instrumental and documentary proxy data. Overall, five findings have been identified: (1) Isotopic ratios in tree rings most strongly reflect conditions of the current growing season, (2) temporally stable climate signals are found in pine δ13C only, (3) all other correlations between tree ring isotopes and climate are temporally unstable and characterized by shifts in correlation sign and strength, (4) climate signals in oak are strongest in the 20th century, and (5) tree ring δ13C reflects local climatic conditions while δ18O is influenced by large‐scale synoptic circulation. The nonstationary relationships observed could reflect changes in the relationship between the climate variables or a physiological adaptation to warmer conditions. Our results provide a cautionary note for the calibration of long tree ring series with 20th century relationships, at least for trees located at ecologically nonextreme sites.
Casein phosphopeptide-amorphous calcium phosphate (CPP-ACP) nanocomplexes incorporated into sugar-free chewing gum have been shown to remineralize enamel subsurface lesions in situ. The aim of this ...study was to compare the ability of CPP-ACP, with that of other forms of calcium, to be retained in supragingival plaque and remineralize enamel subsurface lesions in situ when delivered in a mouthrinse or sugar-free gum in randomized, double-blind trials. In the mouthrinse study, only the CPP-ACP-containing mouthrinse significantly increased plaque calcium and inorganic phosphate levels, and the CPP were immunolocalized to the surfaces of bacterial cells as well as the intercellular matrix. In the chewing gum studies, the gum containing the CPP-ACP, although not containing the most calcium per piece of gum, produced the highest level of enamel remineralization independent of gum-chewing frequency and duration. The CPP could be detected in plaque extracts 3 hrs after subjects chewed the CPP-ACP-containing gum. The results showed that CPP-ACP were superior to other forms of calcium in remineralizing enamel subsurface lesions.
Summary
Background
Patients with psoriasis and clinicians are concerned that infliximab may be associated with a risk of serious infections.
Objectives
To compare the risk of serious infections ...associated with infliximab in patients with chronic plaque psoriasis against a cohort on nonbiologic systemic therapies.
Methods
A prospective cohort study was performed using data from the British Association of Dermatologists Biologic Interventions Register (BADBIR). Infliximab was compared with nonbiologic systemic therapies, inclusive of any exposure to methotrexate, ciclosporin, acitretin, fumaric acid esters, psoralen‐ultraviolet A or hydroxycarbamide. Serious infections were those associated with hospitalization, the use of intravenous antimicrobial therapy and/or those that led to death. Propensity score inverse probability treatment weights were used to adjust for potential confounding from a priori identified covariates. Cox proportional hazards models were calculated to obtain hazard ratios (HRs).
Results
In total, 3843 participants were included for analysis up to October 2016. The incidence rates were significantly higher in the infliximab cohort (47·8 per 1000 person‐years) 95% confidence interval (CI) 35·7–64·0, compared with 14·2 per 1000 person‐years (95% CI 11·5–17·4) in the nonbiologic systemic cohort. Infliximab was associated with an overall increase in the risk of serious infection compared with nonbiologics adjusted HR (adjHR) 1·95, 95% CI 1·01–3·75 and methotrexate only (adjHR 2·96, 95% CI 1·58–5·57) and a higher risk of serious infection in the first 6 months of therapy (adjHR 3·49, 95% CI 1·14–10·70).
Conclusions
Infliximab is associated with an increased risk of serious infections compared with nonbiologic systemic therapies in patients with psoriasis in the U.K. and the Republic of Ireland.
What's already known about this topic?
Randomized clinical trials are not sufficiently powered to investigate the risk of serious infection in patients with psoriasis who are undergoing treatment with infliximab.
Published observational studies have used different methods to adjust for confounding and different comparators.
Previous studies also lacked the adequate sample size to obtain a precise estimate of the risk of serious infection for infliximab.
What does this study add?
Using methods that better address bias and confounding, our study suggests that infliximab is associated with a higher risk of serious infections compared with nonbiologic systemic therapies in patients with psoriasis.
Patients should be counselled on the risk of serious infection before infliximab is prescribed.
Linked Comment: Puig. Br J Dermatol 2019; 180: 257–258.
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