The vegetation history of an Amazonian domed peatland

The peatland pole forests of the Pastaza-Marañón Foreland Basin (PMFB), Peru, are the most carbon-dense ecosystems known in Amazonia once below ground carbon stores are taken into account. Here we present the first multiproxy palaeoenvironmental record including pollen data from one of these peatlands, San Jorge in northern Peru, supported by an age model based on radiocarbon and 210Pb dating. The pollen data indicate that vegetation changes during the early phases of peat initiation resulted from autogenic succession in combination with fluvial influence. The overall pattern of vegetation change is not straightforward: the record does not reflect a process of unidirectional, progressive terrestrialization, but includes a reversal in the succession and vegetation transitions, which omit predicted successional phases. This complexity is similar to that seen in the only other existing pollen record from a PMFB peatland, at Quistococha, but contrasts with peat records from Panama and Southeast Asia where successional patterning appears more predictable. Our dating results provide the first evidence from a PMFB peatland that peat accumulation may have been discontinuous, with evidence for reduced rates of peat accumulation, or a possible hiatus, around 1300–400 cal yr BP. An ecological shift from open lake to palm swamp occurs at this time, possibly driven by climatic change. The pollen data indicate that the present pole forest vegetation at San Jorge began to assemble c. 200–150 cal yr BP. Given this young age, it is likely that the pole forest at this site remains in a state of transition

Discontinuing adalimumab in patients with controlled juvenile idiopathic arthritis-associated uveitis (ADJUST—Adalimumab in Juvenile Idiopathic Arthritis-associated Uveitis Stopping Trial): study protocol for a randomised controlled trial

BACKGROUND: Juvenile idiopathic arthritis (JIA)-associated uveitis is a chronic paediatric ocular inflammatory condition that can result in visual impairment. Adalimumab, a tumour necrosis factor (TNF)-alpha inhibitor, effectively controls joint and eye inflammation; however, its long-term use may increase the risk of adverse health outcomes and place an undue financial burden on the patient and healthcare system given its high cost. There is great interest for patients to stop adalimumab following remission due to these reasons but there is a lack of information on the ability to maintain control after discontinuing adalimumab. METHODS: The Adalimumab in Juvenile Idiopathic Arthritis-associated Uveitis Trial (ADJUST) is a multicentred, international trial that will randomise 118 participants aged 2 years and older with controlled JIA-associated uveitis to either continue adalimumab or discontinue adalimumab and receive a placebo. The trial will compare the time to uveitis recurrence between the two groups over 12 months. All participants will receive the standard weight-based dose of adalimumab or placebo: 20 mg biweekly (if < 30 kg) or 40 mg biweekly (if ≥ 30 kg). DISCUSSION: This is the first randomised controlled trial to assess the efficacy of discontinuing adalimumab after demonstrating control of JIA-associated uveitis for at least 12 months. The results of ADJUST will provide information on clinical outcomes to guide clinicians in their decision-making regarding discontinuation of adalimumab. TRIAL REGISTRATION: ClinicalTrials.gov NCT03816397. Registered on 25 January 2019. EudraCT 2019-000412-29. Registered on 17 January 201

Do Combinations of Behavior Change Techniques That Occur Frequently in Interventions Reflect Underlying Theory?

BACKGROUND: Behavioral interventions typically include multiple behavior change techniques (BCTs). The theory informing the selection of BCTs for an intervention may be stated explicitly or remain unreported, thus impeding the identification of links between theory and behavior change outcomes. PURPOSE: This study aimed to identify groups of BCTs commonly occurring together in behavior change interventions and examine whether behavior change theories underlying these groups could be identified. METHODS: The study involved three phases: (a) a factor analysis to identify groups of co-occurring BCTs from 277 behavior change intervention reports; (b) examining expert consensus (n = 25) about links between BCT groups and behavioral theories; (c) a comparison of the expert-linked theories with theories explicitly mentioned by authors of the 277 intervention reports. RESULTS: Five groups of co-occurring BCTs (range: 3-13 BCTs per group) were identified through factor analysis. Experts agreed on five links (≥80% of experts), comprising three BCT groups and five behavior change theories. Four of the five BCT group-theory links agreed by experts were also stated by study authors in intervention reports using similar groups of BCTs. CONCLUSIONS: It is possible to identify groups of BCTs frequently used together in interventions. Experts made shared inferences about behavior change theory underlying these BCT groups, suggesting that it may be possible to propose a theoretical basis for interventions where authors do not explicitly put forward a theory. These results advance our understanding of theory use in multicomponent interventions and build the evidence base for further understanding theory-based intervention development and evaluation

Reconstructing ‘the Alcoholic’: Recovering from Alcohol Addiction and the Stigma this Entails

Public perception of alcohol addiction is frequently negative, whilst an important part of recovery is the construction of a positive sense of self. In order to explore how this might be achieved, we investigated how those who self-identify as in recovery from alcohol problems view themselves and their difficulties with alcohol and how they make sense of others’ responses to their addiction. Semi-structured interviews with six individuals who had been in recovery between 5 and 35 years and in contact with Alcoholics Anonymous were analysed using Interpretative Phenomenological Analysis. The participants were acutely aware of stigmatising images of ‘alcoholics’ and described having struggled with a considerable dilemma in accepting this identity themselves. However, to some extent they were able to resist stigma by conceiving of an ‘aware alcoholic self’ which was divorced from their previously unaware self and formed the basis for a new more knowing and valued identity

Effects of diabetes and hypertension on macrophage infiltration and matrix expansion in the rat kidney

BACKGROUND: In experimental models of diabetes mellitus, aggravation of renal injury by concomitant hypertension has been described. Inflammatory mechanisms contribute to renal damage in both diseases. We investigated whether hypertension and diabetes mellitus act synergistically to induce macrophage infiltration and matrix expansion in the kidney. METHODS: Insulin-dependent diabetes mellitus was induced by streptozotocin injections to hypertensive mRen2-transgenic rats (TGR) and normotensive Sprague-Dawley control rats. Quantitative immunohistochemical examination of kidney tissue sections was used to measure macrophage infiltration and matrix expansion. The expression of MCP-1, Osteopontin, RANTES, ICAM-1 and VCAM-1 was evaluated by real-time RT-PCR. The localization of MCP-1 was studied by immunohistochemistry. RESULTS: Macrophage infiltration was present in the kidney of normotensive diabetic rats. Hypertensive rats exhibited a more marked infiltration of macrophages, regardless of whether diabetes was present or not. Gene expression of ICAM-1, VCAM-1 and RANTES was unaltered whereas Osteopontin and MCP-1 were induced by hypertension. Immunoreactive MCP-1 was slightly increased in diabetic rat kidney podocytes, and more markedly increased in hypertensive animals. Glomerular matrix accumulation was induced by diabetes and hypertension to a similar degree, and was highest in hypertensive, diabetic animals. CONCLUSION: Diabetes mellitus caused a mild, and angiotensin-dependent hypertension a more marked infiltration of macrophages in the kidney. Combination of both diseases led to additive effects on matrix expansion but not on inflammation. Hypertension appears to be a much stronger stimulus for inflammation of the kidney than STZ diabetes, at least in mRen2-transgenic rats

The Effects of Previous Error and Success in Alzheimer’s Disease and Mild Cognitive Impairment

This work investigated in Alzheimer’s disease dementia (AD), whether the probability of making an error on a task (or a correct response) was influenced by the outcome of the previous trials. We used the antisaccade task (AST) as a model task given the emerging consensus that it provides a promising sensitive and early biological test of cognitive impairment in AD. It can be employed equally well in healthy young and old adults, and in clinical populations. This study examined eye-movements in a sample of 202 participants (42 with dementia due to AD; 65 with mild cognitive impairment (MCI); 95 control participants). The findings revealed an overall increase in the frequency of AST errors in AD and MCI compared to the control group, as predicted. The errors on the current trial increased in proportion to the number of consecutive errors on the previous trials. Interestingly, the probability of errors was reduced on the trials that followed a previously corrected error, compared to the trials where the error remained uncorrected, revealing a level of adaptive control in participants with MCI or AD dementia. There was an earlier peak in the AST distribution of the saccadic reaction times for the inhibitory errors in comparison to the correct saccades. These findings revealed that the inhibitory errors of the past have a negative effect on the future performance of healthy adults as well as people with a neurodegenerative cognitive impairment

High-speed fixed-target serial virus crystallography

We report a method for serial X-ray crystallography at X-ray free-electron lasers (XFELs), which allows for full use of the current 120-Hz repetition rate of the Linear Coherent Light Source (LCLS). Using a micropatterned silicon chip in combination with the high-speed Roadrunner goniometer for sample delivery, we were able to determine the crystal structures of the picornavirus bovine enterovirus 2 (BEV2) and the cytoplasmic polyhedrosis virus type 18 polyhedrin, with total data collection times of less than 14 and 10 min, respectively. Our method requires only micrograms of sample and should therefore broaden the applicability of serial femtosecond crystallography to challenging projects for which only limited sample amounts are available. By synchronizing the sample exchange to the XFEL repetition rate, our method allows for most efficient use of the limited beam time available at XFELs and should enable a substantial increase in sample throughput at these facilities

Anticancer Gene Transfer for Cancer Gene Therapy

Gene therapy vectors are among the treatments currently used to treat malignant tumors. Gene therapy vectors use a specific therapeutic transgene that causes death in cancer cells. In early attempts at gene therapy, therapeutic transgenes were driven by non-specific vectors which induced toxicity to normal cells in addition to the cancer cells. Recently, novel cancer specific viral vectors have been developed that target cancer cells leaving normal cells unharmed. Here we review such cancer specific gene therapy systems currently used in the treatment of cancer and discuss the major challenges and future directions in this field