"Those who cannot remember the past are condemned to repeat it." George Santayana 1905 "If men could learn from history, what lessons it might teach us! But passion and party blind our eyes, and the ...light which experience gives is a lantern on the stern, which shines only on the waves behind us!" Samuel Taylor Coleridge 1835 The medical speciality of theranostic nuclear oncology has taken three-quarters of a century to move the stern light cast retrospectively by single-centre clinical reports, to the forepeak in the bow of our theranostic craft, where prospective randomised controlled multicentre clinical trials now illuminate the way forward. This recent reorientation of nuclear medicine clinical research practice to align with that of standard medical and radiation oncology protocols, reflects the paradigm shift toward individualised molecular oncology and precision medicine. Theranostics is the epitome of personalised medicine. The specific tumour biomarker is quantitatively imaged on positron emission tomography (PET)/CT or single photon emission computed tomography (SPECT)/CT. If it is clearly demonstrated that a tumoricidal radiation absorbed dose can be delivered, the theranostic beta or alpha-emitting radionuclide pair, coupled to the same targeted molecule, is then administered, to control advanced metastatic cancer in that individual patient. This prior selection of patients who may benefit from theranostic treatment is in direct contrast to the evolving oncological indirect treatments using immune-check point inhibitors, where there is an urgent need to define biomarkers which can reliably predict response, and thus avoid the high cost and toxicity of these agents in patients who are unlikely to benefit. The immune and molecular treatment approaches of oncology are a recent phenomenon and the efficacy and safety of immune-check point blockade and chimeric antigen receptor T-cell therapies are currently under evaluation in multicentre randomised controlled trials. Such objective evaluation is compromised by the inadequacy of conventional response evaluation criteria in solid tumour (RECIST) CT/MR anatomical/functional imaging to define tumour response, in both immune-oncology and theranostic nuclear oncology. This introduction to the clinical practice of theranostics explores ways in which nuclear physicians can learn from the lessons of history, and join with their medical, surgical and radiation oncology colleagues to establish a symbiotic collaboration to realise the potential of personalised molecular medicine to control advanced cancer and actually enhance quality of life whilst prolonging survival.
Interpreting contemporary trends in atmospheric methane Turner, Alexander J.; Frankenberg, Christian; Kort, Eric A.
Proceedings of the National Academy of Sciences - PNAS,
02/2019, Letnik:
116, Številka:
8
Journal Article
Recenzirano
Odprti dostop
Atmospheric methane plays a major role in controlling climate, yet contemporary methane trends (1982–2017) have defied explanation with numerous, often conflicting, hypotheses proposed in the ...literature. Specifically, atmospheric observations of methane from 1982 to 2017 have exhibited periods of both increasing concentrations (from 1982 to 2000 and from 2007 to 2017) and stabilization (from 2000 to 2007). Explanations for the increases and stabilization have invoked changes in tropical wetlands, livestock, fossil fuels, biomass burning, and the methane sink. Contradictions in these hypotheses arise because our current observational network cannot unambiguously link recent methane variations to specific sources. This raises some fundamental questions: (i) What do we know about sources, sinks, and underlying processes driving observed trends in atmospheric methane? (ii) How will global methane respond to changes in anthropogenic emissions? And (iii), What future observations could help resolve changes in the methane budget? To address these questions, we discuss potential drivers of atmospheric methane abundances over the last four decades in light of various observational constraints as well as process-based knowledge. While uncertainties in the methane budget exist, they should not detract from the potential of methane emissions mitigation strategies. We show that net-zero cost emission reductions can lead to a declining atmospheric burden, but can take three decades to stabilize. Moving forward, we make recommendations for observations to better constrain contemporary trends in atmospheric methane and to provide mitigation support.
The current study systematically reviewed, summarized and meta-analyzed the clinical features of the vaccines in clinical trials to provide a better estimate of their efficacy, side effects and ...immunogenicity. All relevant publications were systematically searched and collected from major databases up to 12 March 2021. A total of 25 RCTs (123 datasets), 58,889 cases that received the COVID-19 vaccine and 46,638 controls who received placebo were included in the meta-analysis. In total, mRNA-based and adenovirus-vectored COVID-19 vaccines had 94.6% (95% CI 0.936–0.954) and 80.2% (95% CI 0.56–0.93) efficacy in phase II/III RCTs, respectively. Efficacy of the adenovirus-vectored vaccine after the first (97.6%; 95% CI 0.939–0.997) and second (98.2%; 95% CI 0.980–0.984) doses was the highest against receptor-binding domain (RBD) antigen after 3 weeks of injections. The mRNA-based vaccines had the highest level of side effects reported except for diarrhea and arthralgia. Aluminum-adjuvanted vaccines had the lowest systemic and local side effects between vaccines’ adjuvant or without adjuvant, except for injection site redness. The adenovirus-vectored and mRNA-based vaccines for COVID-19 showed the highest efficacy after first and second doses, respectively. The mRNA-based vaccines had higher side effects. Remarkably few experienced extreme adverse effects and all stimulated robust immune responses.
In this article Rational Emotive Behavior Therapy (REBT) is proposed as a potentially important framework for the understanding and promotion of mental health in athletes. Cognitive-behavioral ...approaches predominate in the provision of sport psychology, and often form the backbone of psychological skills training for performance enhancement and maintenance. But far from being solely performance-focused, the cognitive-behavioral approach to sport psychology can restore, promote, and maintain mental health. This review article presents REBT (Ellis, 1957), the original cognitive behavioral therapy, as a valuable approach to addressing mental health issues in sport. REBT holds that it is not events that directly cause emotions and behaviors. Rather, it is one's beliefs about the events that lead to emotional and behavioral reactivity. Further, REBT distinguishes between rational and irrational beliefs, and suggests that in response to failure, maltreatment, and misfortune, people can react with either healthy or unhealthy emotional and behavioral responses. The extant research indicates that irrational beliefs lead to unhealthy negative emotions, a range of pathological conditions, and a host of maladaptive behaviors that undermine mental health. Therefore, REBT proposes a process for the reduction of irrational beliefs and the promotion of rational beliefs. The use of REBT in sport is seldom reported in literature, but research is growing. This review article proposes three important areas of investigation that will aid the understanding of irrational beliefs and the application of REBT within sport. These areas are: (1) the influence of irrational beliefs and REBT on the mental health of athletes, (2) the influence of irrational beliefs and REBT on athletic performance, (3) the origins and development of irrational beliefs in athletes. Each area is discussed in turn, offering a critical and progressive review of the literature as well as highlighting research deficits, and recommendations to address each of the three areas of investigation.
Theranostic nuclear oncology is on the cusp of adoption into routine clinical management of neuroendocrine tumours (NETs) following publication of the Phase 3 randomised controlled trial, NETTER-1. ...For the first time, level 1b evidence of efficacy and safety of 68-gallium/177-lutetium-DOTA-octreotate peptide receptor radionuclide therapy, of mid-gut neuroendocrine tumours was established. Multicentre Phase 2 studies of 68-gallium/177-lutetium-prostate specific membrane antigen theranostic approaches to management of end-stage metastatic castrate-resistant prostate cancer, are also very encouraging. However, the retrospective uncontrolled data currently available are inadmissible for formal regulatory agency evaluation. The challenge is to engage with oncologists and urologists, and to collaborate with the pharmaceutical industry, to design and perform the controlled clinical trials required for regulatory approval, and eventual reimbursement for theranostic nuclear oncology procedures. Strategies to facilitate timely establishment of an evidence base are considered in this review of theranostic advances over the past year. The prime objective is the provision of novel, effective, safe, personalised, tumour-targeted molecular theranostic management of metastatic castrate-resistant prostate cancer, and other cancers, such as non-Hodgkin lymphoma, which express the appropriate molecular receptor tumour targets. It would also be desirable to offer theranostic treatments at an earlier stage of malignant disease when the benefit is likely to be greater. The ultimate goal of theranostic nuclear oncology is to prolong survival and to improve quality of life for cancer patients worldwide. This may only be achieved through close collaboration between oncologists, nuclear physicians, radiologists, dosimetric physicists, Pharma, and, above all, with the patients themselves, in ways which are explored in this review.
This white paper provides a summary of a scientific proposal presented at a Cardiac Safety Research Consortium/Health and Environmental Sciences Institute/Food and Drug Administration–sponsored Think ...Tank, held at Food and Drug Administration's White Oak facilities, Silver Spring, MD, on July 23, 2013, with the intention of moving toward consensus on defining a new paradigm in the field of cardiac safety in which proarrhythmic risk would be primarily assessed using nonclinical in vitro human models based on solid mechanistic considerations of torsades de pointes proarrhythmia. This new paradigm would shift the emphasis from the present approach that strongly relies on QTc prolongation (a surrogate marker of proarrhythmia) and could obviate the clinical Thorough QT study during later drug development. These discussions represent current thinking and suggestions for furthering our knowledge and understanding of the public health case for adopting a new, integrated nonclinical in vitro/in silico paradigm, the Comprehensive In Vitro Proarrhythmia Assay, for the assessment of a candidate drug's proarrhythmic liability, and for developing a public-private collaborative program to characterize the data content, quality, and approaches required to assess proarrhythmic risk in the absence of a Thorough QT study. This paper seeks to encourage multistakeholder input regarding this initiative and does not represent regulatory guidance.
Over 90% of prostate cancers over-express prostate specific membrane antigen (PSMA) and these tumor cells may be accurately targeted for diagnosis by
Ga-PSMA-positron emission tomography/computed ...tomography (
Ga-PSMA-PET/CT) imaging. This novel molecular imaging modality appears clinically to have superseded CT, and appears superior to MR imaging, for the detection of metastatic disease.
Ga-PSMA PET/CT has the ability to reliably stage prostate cancer at presentation and can help inform an optimal treatment approach. Novel diagnostic applications of
Ga-PSMA PET/CT include guiding biopsy to improve sampling accuracy, and guiding surgery and radiotherapy. In addition to facilitating the management of metastatic castrate resistant prostate cancer (mCRPC),
Ga-PSMA can select patients who may benefit from targeted systemic radionuclide therapy.
Ga-PSMA is the diagnostic positron-emitting theranostic pair with the beta emitter Lutetium-177 PSMA (
Lu-PSMA) and alpha-emitter Actinium-225 PSMA (
Ac-PSMA) which can both be used to treat PSMA-avid metastases of prostate cancer in the molecular tumor-targeted approach of theranostic nuclear oncology.
Recent developments of stereoselective biocatalytic and chemocatalytic methods are discussed. The review provides a guide to the use of biocatalytic methods in the area of chemical synthesis with ...focused attention on retrosynthetic considerations and analysis. The transformations presented are organized according to bond disconnections and attendant synthetic methods. The review is expected to lead to better understanding of the characteristics and distinctions of the two complementary approaches. It depicts for researchers in bio‐ and chemocatalysis a road map of challenges and opportunities for the evolution (and at times revolution) in chemical synthesis.
Partners in synthesis: This Review provides a guide to the use of biocatalytic methods in the area of chemical synthesis with focus on retrosynthetic considerations and analysis. It is expected to lead to better understanding of the characteristics and distinctions of the two complementary approaches by depicting a road map of challenges and opportunities for the evolution in chemical synthesis.
Wetland emissions remain one of the principal sources of uncertainty in the global atmospheric methane (CH4) budget, largely due to poorly constrained process controls on CH4 production in ...waterlogged soils. Process-based estimates of global wetland CH4 emissions and their associated uncertainties can provide crucial prior information for model-based top-down CH4 emission estimates. Here we construct a global wetland CH4 emission model ensemble for use in atmospheric chemical transport models (WetCHARTs version 1.0). Our 0.5° × 0.5° resolution model ensemble is based on satellite-derived surface water extent and precipitation reanalyses, nine heterotrophic respiration simulations (eight carbon cycle models and a data-constrained terrestrial carbon cycle analysis) and three temperature dependence parameterizations for the period 2009–2010; an extended ensemble subset based solely on precipitation and the data-constrained terrestrial carbon cycle analysis is derived for the period 2001–2015. We incorporate the mean of the full and extended model ensembles into GEOS-Chem and compare the model against surface measurements of atmospheric CH4; the model performance (site-level and zonal mean anomaly residuals) compares favourably against published wetland CH4 emissions scenarios. We find that uncertainties in carbon decomposition rates and the wetland extent together account for more than 80 % of the dominant uncertainty in the timing, magnitude and seasonal variability in wetland CH4 emissions, although uncertainty in the temperature CH4 : C dependence is a significant contributor to seasonal variations in mid-latitude wetland CH4 emissions. The combination of satellite, carbon cycle models and temperature dependence parameterizations provides a physically informed structural a priori uncertainty that is critical for top-down estimates of wetland CH4 fluxes. Specifically, our ensemble can provide enhanced information on the prior CH4 emission uncertainty and the error covariance structure, as well as a means for using posterior flux estimates and their uncertainties to quantitatively constrain the biogeochemical process controls of global wetland CH4 emissions.
Illumination characteristics from artificial sources strongly influence the experimental performance of solar water-splitting devices, with the highest impact on tandem structures designed for ...optimum conversion efficiency. We highlight quantitative and qualitative flaws of common characterization techniques, discuss their impact on research results and strategy, and demonstrate approaches toward advanced measurement accuracy.
Uncontrolled spectral mismatch of laboratory light sources and inappropriate area definitions induce vast inaccuracies for solar-to-hydrogen efficiency measurement and reporting.
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