Climate change is altering the species composition, structure, and function of vegetation in natural terrestrial ecosystems. These changes can also impact the essential ecosystem goods and services ...derived from these ecosystems. Following disturbances, remote-sensing datasets have been used to monitor the disturbance and describe antecedent conditions as a means of understanding vulnerability to change. To a lesser extent, they have also been used to predict when desired ecosystems are vulnerable to degradation or loss. In this paper, we review studies that have applied remote sensing imagery to characterize vegetation vulnerability in both retrospective and prospective modes. We first review vulnerability research in natural terrestrial ecosystems including temperate forests, tropical forests, boreal forests, semi-arid lands, coastal areas, and the arctic. We then evaluate whether remote sensing can evaluate vulnerability sufficiently in advance of future events in order to allow the implementation of mitigation strategies, or whether it can only describe antecedent conditions a posteriori. The majority of existing research has evaluated vulnerability retrospectively, but key studies highlight the considerable potential for the development of early warnings of future vulnerability. We conclude that future research needs to focus on the development of a greater number of remotely sensed metrics to be used in a prospective mode in assessing vulnerability of terrestrial vegetation under change.
•Review of vegetation vulnerability in natural terrestrial ecosystems•Broadly transferable early warning systems require mechanistic metrics•Metrics should bridge between climate impacts and ecosystem services
Background Parathyroidectomy offers the only cure for primary hyperparathyroidism, but today only 50% of primary hyperparathyroidism patients are referred for operation, in large part, because the ...condition is widely under-recognized. The diagnosis of primary hyperparathyroidism can be especially challenging with mild biochemical indices. Machine learning is a collection of methods in which computers build predictive algorithms based on labeled examples. With the aim of facilitating diagnosis, we tested the ability of machine learning to distinguish primary hyperparathyroidism from normal physiology using clinical and laboratory data. Methods This retrospective cohort study used a labeled training set and 10-fold cross-validation to evaluate accuracy of the algorithm. Measures of accuracy included area under the receiver operating characteristic curve, precision (sensitivity), and positive and negative predictive value. Several different algorithms and ensembles of algorithms were tested using the Weka platform. Among 11,830 patients managed operatively at 3 high-volume endocrine surgery programs from March 2001 to August 2013, 6,777 underwent parathyroidectomy for confirmed primary hyperparathyroidism, and 5,053 control patients without primary hyperparathyroidism underwent thyroidectomy. Test-set accuracies for machine learning models were determined using 10-fold cross-validation. Age, sex, and serum levels of preoperative calcium, phosphate, parathyroid hormone, vitamin D, and creatinine were defined as potential predictors of primary hyperparathyroidism. Mild primary hyperparathyroidism was defined as primary hyperparathyroidism with normal preoperative calcium or parathyroid hormone levels. Results After testing a variety of machine learning algorithms, Bayesian network models proved most accurate, classifying correctly 95.2% of all primary hyperparathyroidism patients (area under receiver operating characteristic = 0.989). Omitting parathyroid hormone from the model did not decrease the accuracy significantly (area under receiver operating characteristic = 0.985). In mild disease cases, however, the Bayesian network model classified correctly 71.1% of patients with normal calcium and 92.1% with normal parathyroid hormone levels preoperatively. Bayesian networking and AdaBoost improved the accuracy of all parathyroid hormone patients to 97.2% cases (area under receiver operating characteristic = 0.994), and 91.9% of primary hyperparathyroidism patients with mild disease. This was significantly improved relative to Bayesian networking alone ( P < .0001). Conclusion Machine learning can diagnose accurately primary hyperparathyroidism without human input even in mild disease. Incorporation of this tool into electronic medical record systems may aid in recognition of this under-diagnosed disorder.
The authors performed clinical-pathologic correlation to assess the validity of the Boston diagnostic criteria for cerebral amyloid angiopathy (CAA). Thirteen subjects were diagnosed clinically with ...probable CAA from among 39 patients with available pathologic tissue in a prospective cohort of subjects aged > or = 55 years with primary lobar hemorrhage. All 13 individuals were confirmed neuropathologically as having CAA. This small pathologic series indicates that the diagnosis of probable CAA can be made during life with high accuracy.
To review critically the past 10 years of research on youth suicide.
Research literature on youth suicide was reviewed following a systematic search of PsycINFO and Medline. The search for ...school-based suicide prevention programs was expanded using two education databases: ERIC and Education Full Text. Finally, manual reviews of articles' reference lists identified additional studies. The review focuses on epidemiology, risk factors, prevention strategies, and treatment protocols.
There has been a dramatic decrease in the youth suicide rate during the past decade. Although a number of factors have been posited for the decline, one of the more plausible ones appears to be the increase in antidepressants being prescribed for adolescents during this period. Youth psychiatric disorder, a family history of suicide and psychopathology, stressful life events, and access to firearms are key risk factors for youth suicide. Exciting new findings have emerged on the biology of suicide in adults, but, while encouraging, these are yet to be replicated in youths. Promising prevention strategies, including school-based skills training for students, screening for at-risk youths, education of primary care physicians, media education, and lethal-means restriction, need continuing evaluation studies. Dialectical behavior therapy, cognitive-behavioral therapy, and treatment with antidepressants have been identified as promising treatments but have not yet been tested in a randomized clinical trial of youth suicide.
While tremendous strides have been made in our understanding of who is at risk for suicide, it is incumbent upon future research efforts to focus on the development and evaluation of empirically based suicide prevention and treatment protocols.
Although inositol pyrophosphates have diverse roles in phosphate signaling and other important cellular processes, little is known about their functions in the biosynthesis of inositol and ...phospholipids. Here, we show that KCS1, which encodes an inositol pyrophosphate kinase, is a regulator of inositol metabolism. Deletion of KCS1, which blocks synthesis of inositol pyrophosphates on the 5-hydroxyl of the inositol ring, causes inositol auxotrophy and decreased intracellular inositol and phosphatidylinositol. These defects are caused by a profound decrease in transcription of INO1, which encodes myo-inositol-3-phosphate synthase. Expression of genes that function in glycolysis, transcription, and protein processing is not affected in kcs1Δ. Deletion of OPI1, the INO1 transcription repressor, does not fully rescue INO1 expression in kcs1Δ. Both the inositol pyrophosphate kinase and the basic leucine zipper domains of KCS1 are required for INO1 expression. Kcs1 is regulated in response to inositol, as Kcs1 protein levels are increased in response to inositol depletion. The Kcs1-catalyzed production of inositol pyrophosphates from inositol pentakisphosphate but not inositol hexakisphosphate is indispensable for optimal INO1 transcription. We conclude that INO1 transcription is fine-tuned by the synthesis of inositol pyrophosphates, and we propose a model in which modulation of Kcs1 controls INO1 transcription by regulating synthesis of inositol pyrophosphates.
Background: Regulation of inositol metabolism is crucial for cellular functions.
Results: Inositol pyrophosphate-deficient cells exhibit defective inositol biosynthesis. Protein levels of the inositol pyrophosphate biosynthetic enzyme Kcs1 are dynamically altered in response to inositol.
Conclusion: INO1 transcription and inositol biosynthesis are regulated by modulation of inositol pyrophosphate synthesis.
Significance: Inositol pyrophosphates are novel regulators of biosynthesis of inositol and inositol phospholipids.
Oral Diseases (2011) 17 (Suppl. 1), 73–84
There are few topical formulations used for oral medicine applications most of which have been developed for the management of dermatological conditions. As ...such, numerous obstacles are faced when utilizing these preparations in the oral cavity, namely enzymatic degradation, taste, limited surface area, poor tissue penetration and accidental swallowing. In this review, we discuss common mucosal diseases such as oral cancer, mucositis, vesiculo‐erosive conditions, infections, neuropathic pain and salivary dysfunction, which could benefit from topical delivery systems designed specifically for the oral mucosa, which are capable of sustained release. Each condition requires distinct penetration and drug retention profiles in order to optimize treatment and minimize side effects. Local drug delivery may provide a more targeted and efficient drug‐delivery option than systemic delivery for diseases of the oral mucosa. We identify those mucosal diseases currently being treated, the challenges that must be overcome and the potential of novel therapies. Novel biological therapies such as macromolecular biological drugs, peptides and gene therapy may be of value in the treatment of many chronic oral conditions and thus in oral medicine if their delivery can be optimized.
Functional neuroimaging studies of episodic memory retrieval generally measure brain activity while participants remember items encountered in the laboratory (“controlled laboratory condition”) or ...events from their own life (“open autobiographical condition”). Differences in activation between these conditions may reflect differences in retrieval processes, memory remoteness, emotional content, retrieval success, self-referential processing, visual/spatial memory, and recollection. To clarify the nature of these differences, a functional MRI study was conducted using a novel “photo paradigm,” which allows greater control over the autobiographical condition, including a measure of retrieval accuracy. Undergraduate students took photos in specified campus locations (“controlled autobiographical condition”), viewed in the laboratory similar photos taken by other participants (controlled laboratory condition), and were then scanned while recognizing the two kinds of photos. Both conditions activated a common episodic memory network that included medial temporal and prefrontal regions. Compared with the controlled laboratory condition, the controlled autobiographical condition elicited greater activity in regions associated with self-referential processing (medial prefrontal cortex), visual/ spatial memory (visual and parahippocampal regions), and recollection (hippocampus). The photo paradigm provides a way of investigating the functional neuroanatomy of real-life episodic memory under rigorous experimental control.
Elevated plasma total homocysteine (tHcy) is a risk factor for cardiovascular disease and is reported to be an independent risk factor for Alzheimer disease (AD) and cognitive decline. tHcy may ...potentiate neurotoxic and vasculopathic processes, including amyloid beta protein (Abeta) metabolism, implicated in neurodegenerative diseases.
To examine the relationship of plasma total tHcy levels with clinical, demographic, biochemical, and genetic factors in aging, mild cognitive impairment (MCI), AD, cerebral amyloid angiopathy (CAA), and Parkinson disease (PD).
Plasma tHcy, folate, vitamin B(12), creatinine, and Abeta levels were assessed in individuals evaluated in the Memory, Stroke, and Movement Disorders Units of Massachusetts General Hospital with diagnoses of AD (n = 145), MCI (n = 47), PD (n = 93), CAA (67), hypertensive intracerebral hemorrhage (hICH) (n = 25), and no dementia (n = 88).
The tHcy levels did not differ across AD, MCI, CAA, hICH, and nondemented control subjects but were increased in the PD group (p < 0.01). The elevated levels within the PD group were due to high tHcy in individuals taking levodopa (p < 0.0001). Increasing tHcy was associated with worse cognition in the PD cases, but not the other diagnostic groups. tHcy levels positively correlated with plasma Abeta levels even after adjustments for age and creatinine (p < 0.0001).
Mean tHcy levels increased with age but did not discriminate diagnostic groups aside from significant elevation in patients with PD taking levodopa. The positive association between tHcy and plasma Abeta levels raises the possibility that these circulating factors could interact to affect AD risk and cognition in PD.
Summary
Background
Tumour necrosis factor (TNF)‐antagonists have an established role in the treatment of inflammatory bowel diseases (IBDs), however, subtherapeutic drug levels and the formation of ...anti‐drug antibodies (ADAs) may decrease their efficacy.
Aim
The evidence supporting the use of therapeutic drug monitoring (TDM) based clinical algorithms for infliximab (IFX) and their role in clinical practice will be discussed.
Methods
The literature was reviewed to identify relevant articles on the measurement of IFX levels and antibodies‐to‐infliximab.
Results
Treatment algorithms for IBD have evolved from episodic monotherapy used in patients refractory to all other treatments, to long‐term combination therapy initiated early in the disease course. Improved remission rates have been observed with this paradigm shift, nevertheless many patients ultimately lose response to therapy. Although empiric dose optimization or switching agents constitute the current standard of care for secondary failure, these interventions have not been applied in an evidence‐based manner and are probably not cost‐effective. Multiple TDM‐based algorithms have been developed to identify patients that may benefit from measurement of IFX and ADA levels to guide adjustments to therapy.
Conclusions
Therapeutic drug monitoring offers a rational approach to the management of secondary failure to IFX. This concept has gained momentum based on evidence from case series, cohort studies and post‐hoc analyses of randomised controlled trials.
OBJECTIVES
To determine the effect of preload in color M-mode Doppler flow propagation velocity (vp).
BACKGROUND
The interpretation of Doppler filling patterns is limited by confounding effects of ...left ventricular (LV) relaxation and preload. Color M-mode vphas been proposed as a new index of LV relaxation.
METHODS
We studied four dogs before and during inferior caval (IVC) occlusion at five different inotropic stages and 14 patients before and during partial cardiopulmonary bypass. Left ventricular (LV) end-diastolic volumes (LV-EDV), the time constant of isovolumic relaxation (tau), left atrial (LA) pre-A and LV end-diastolic pressures (LV-EDP) were measured. Peak velocity during early filling (E) and vpwere extracted by digital analysis of color M-mode Doppler images.
RESULTS
In both animals and humans, LV-EDV and LV-EDP decreased significantly from baseline to IVC occlusion (both p < 0.001). Peak early filling (E) velocity decreased in animals from 56 ± 21 to 42 ± 17 cm/s (p < 0.001) without change in vp(from 35 ± 15 to 35 ± 16, p = 0.99). Results were similar in humans (from 69 ± 15 to 53 ± 22 cm/s, p < 0.001, and 37 ± 12 to 34 ± 16, p = 0.30). In both species, there was a strong correlation between LV relaxation (tau) and vp(r = 0.78, p < 0.001, r = 0.86, p < 0.001).
CONCLUSIONS
Our results indicate that color M-mode Doppler vpis not affected by preload alterations and confirms that LV relaxation is its main physiologic determinant in both animals during varying lusitropic conditions and in humans with heart disease.
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