The Carbon Market Challenge : Preventing Abuse Through Effective Governance

Carbon markets – both emission trading systems and baseline and credit systems – are an increasingly common policy instrument being introduced to address climate change mitigation. However, their design is crucial to ensure that they deliver cost-effective emission reductions while maintaining environmental integrity. This Element puts together a comprehensive, principle-based overview of the risks and abuses to environmental integrity and cost effectiveness that have emerged for carbon markets at all jurisdictional levels around the world, provides concrete examples, and offers effective policy and governance solutions to overcome such risks. This title is also available as Open Access on Cambridge Core

Impairments of postural control, functional performance and strength in morbidly obese patients awaiting bariatric surgery in comparison to healthy individuals

There is a lack of information evaluating specific markers of performance in patients awaiting bariatric surgery. We aimed to assess the postural control, functional performance, strength and endurance performance for morbidly obese patients awaiting bariatric surgery compared to lean controls. [Subjects and Methods] All parameters were assessed by modified Y-balance test, timed-up-and-go-test, maximum strength testing on resistance exercise equipment and cardio-pulmonary exercise testing on a cycle ergometer in 10 morbidly obese patients awaiting bariatric surgery and 10 age- and sex-matched lean controls. [Results] It was found that significant differences existed for overall modified Y-balance test in morbidly obese patients awaiting bariatric surgery versus lean controls (0.37 ± 0.03 vs. 0.47 ± 0.02 cm.cm−1), timed-up-and-go-test (9.33 ± 1.23 vs. 7.85 ± 1.73 sec) and several variables of cardio-pulmonary exercise testing. Overall absolute strength expressed in kilogram was similar, yet when relativized to body weight strength differences were notable (0.4 ± 0.17 vs. 0.83 ± 0.32 kg.kg−1). [Conclusion] The results of this study demonstrate the need for comprehensive functional assessment prior to surgery with an identified demand for subsequent tailored physical training prescription that should begin before surgery

NS1 Specific CD8(+) T-Cells with Effector Function and TRBV11 Dominance in a Patient with Parvovirus B19 Associated Inflammatory Cardiomyopathy

Background: Parvovirus B19 (B19V) is the most commonly detected virus in endomyocardial biopsies (EMBs) from patients with inflammatory cardiomyopathy (DCMi). Despite the importance of T-cells in antiviral defense, little is known about the role of B19V specific T-cells in this entity. Methodology and Principal Findings: An exceptionally high B19V viral load in EMBs (115,091 viral copies/mg nucleic acids), peripheral blood mononuclear cells (PBMCs) and serum was measured in a DCMi patient at initial presentation, suggesting B19V viremia. The B19V viral load in EMBs had decreased substantially 6 and 12 months afterwards, and was not traceable in PBMCs and the serum at these times. Using pools of overlapping peptides spanning the whole B19V proteome, strong CD8(+) T-cell responses were elicited to the 10-amico-acid peptides SALKLAIYKA (19.7% of all CD8(+) cells) and QSALKLAIYK (10%) and additional weaker responses to GLCPHCINVG (0.71%) and LLHTDFEQVM (0.06%). Real-time RT-PCR of IFN gamma secretion-assay-enriched T-cells responding to the peptides, SALKLAIYKA and GLCPHCINVG, revealed a disproportionately high T-cell receptor Vbeta (TRBV) 11 expression in this population. Furthermore, dominant expression of type-1 (IFN gamma, IL2, IL27 and Tbet) and of cytotoxic T-cell markers (Perforin and Granzyme B) was found, whereas gene expression indicating type-2 (IL4, GATA3) and regulatory T-cells (FoxP3) was low. Conclusions: Our results indicate that B19V Ag-specific CD8(+) T-cells with effector function are involved in B19V associated DCMi. In particular, a dominant role of TRBV11 and type-1/CTL effector cells in the T-cell mediated antiviral immune response is suggested. The persistence of B19V in the endomyocardium is a likely antigen source for the maintenance of CD8(+) T-cell responses to the identified epitopes

Temporary antimetabolite treatment hold boosts SARS-CoV-2 vaccination–specific humoral and cellular immunity in kidney transplant recipients

Transplant recipients exhibit an impaired protective immunity after SARS-CoV-2 vaccination, potentially caused by mycophenolate (MPA) immunosuppression. Recent data from patients with autoimmune disorders suggest that temporary MPA hold might greatly improve booster vaccination outcomes. We applied a fourth dose of SARS-CoV-2 vaccine to 29 kidney transplant recipients during a temporary (5 weeks) MPA/azathioprine hold, who had not mounted a humoral immune response to previous vaccinations. Seroconversion until day 32 after vaccination was observed in 76% of patients, associated with acquisition of virus-neutralizing capacity. Interestingly, 21/25 (84%) calcineurin inhibitor-treated patients responded, but only 1/4 belatacept-treated patients responded. In line with humoral responses. counts and relative frequencies of spike receptor binding domain-specific (RBD-specific) B cells were markedly increased on day 7 after vaccination, with an increase in RBD-specific CD27(++)CD38(+) plasmablasts. Whereas overall proportions of spike-reactive CD4(+) T cells remained unaltered after the fourth dose, frequencies were positively correlated with specific IgG levels. Importantly, antigen-specific proliferating Ki67(+) and in vivo-activated programmed cell death 1-positive T cells significantly increased after revaccination during MPA hold, whereas cytokine production and memory differentiation remained unaffected. In summary, antimetabolite hold augmented all arms of immunity during booster vaccination. These data suggest further studies of antimetabolite hold in kidney transplant recipients

Preamplification techniques for real-time RT-PCR analyses of endomyocardial biopsies

<p>Abstract</p> <p>Background</p> <p>Due to the limited RNA amounts from endomyocardial biopsies (EMBs) and low expression levels of certain genes, gene expression analyses by conventional real-time RT-PCR are restrained in EMBs. We applied two preamplification techniques, the TaqMan^®PreAmp Master Mix (T-PreAmp) and a multiplex preamplification following a sequence specific reverse transcription (SSRT-PreAmp).</p> <p>Results</p> <p>T-PreAmp encompassing 92 gene assays with 14 cycles resulted in a mean improvement of 7.24 ± 0.33 Ct values. The coefficients for inter- (1.89 ± 0.48%) and intra-assay variation (0.85 ± 0.45%) were low for all gene assays tested (<4%). The PreAmp uniformity values related to the reference gene CDKN1B for 91 of the investigated gene assays (except for CD56) were -0.38 ± 0.33, without significant differences between self-designed and ABI inventoried Taqman^®gene assays. Only two of the tested Taqman^®ABI inventoried gene assays (HPRT-ABI and CD56) did not maintain PreAmp uniformity levels between -1.5 and +1.5. In comparison, the SSRT-PreAmp tested on 8 self-designed gene assays yielded higher Ct improvement (9.76 ± 2.45), however was not as robust regarding the maintenance of PreAmp uniformity related to HPRT-CCM (-3.29 ± 2.40; p < 0.0001), and demonstrated comparable intra-assay CVs (1.47 ± 0.74), albeit higher inter-assay CVs (5.38 ± 2.06; p = 0.01). Comparing EMBs from each 10 patients with dilated cardiomyopathy (DCM) and inflammatory cardiomyopathy (DCMi), T-PreAmp real-time RT-PCR analyses revealed differential regulation regarding 27 (30%) of the investigated 90 genes related to both HPRT-CCM and CDKN1B. Ct values of HPRT and CDKN1B did not differ in equal RNA amounts from explanted DCM and donor hearts.</p> <p>Conclusion</p> <p>In comparison to the SSRT-PreAmp, T-PreAmp enables a relatively simple workflow, and results in a robust PreAmp of multiple target genes (at least 92 gene assays as tested here) by a mean Ct improvement around 7 cycles, and in a lower inter-assay variance in RNA derived from EMBs. Preliminary analyses comparing EMBs from DCM and DCMi patients, revealing differential regulation regarding 30% of the investigated genes, confirm that T-PreAmp is a suitable tool to perform gene expression analyses in EMBs, expanding gene expression investigations with the limited RNA/cDNA amounts derived from EMBs. CDKN1B, in addition to its function as a reference gene for the calculation of PreAmp uniformity, might serve as a suitable housekeeping gene for real-time RT-PCR analyses of myocardial tissues.</p

The Carbon Market Challenge : Preventing Abuse through Effective Governance

Carbon markets – both emission trading systems and baseline and credit systems – are an increasingly common policy instrument being introduced to address climate change mitigation. However, their design is crucial to ensure that they deliver cost-effective emission reductions while maintaining environmental integrity. This Element puts together a comprehensive, principle-based overview of the risks and abuses to environmental integrity and cost effectiveness that have emerged for carbon markets at all jurisdictional levels around the world, provides concrete examples, and offers effective policy and governance solutions to overcome such risks

Course of clinical parameters, EMBs and serological results.

<p>Evolution of echocardiographic parameters (LVEF, LVEDD: LV enddiastolic diameter), of the B19V quantification results in EMBs and PBMCs (viral copies/μg nucleic acids in EMBs, and viral copies/ml serum, respectively) and of the DIA quantified, immunohistologically marked infiltrates and CAMs expression in EMBs. AF: fraction of area in percent (DIA derived value for CAMs expression). Normal values for DIA quantified infiltrates and CAMs expression in EMBs: CD3: <7/mm², LFA-1: <9/mm², CD45R0: <7/mm², Mac-1: <35/mm², HLA class I: <5.5%, ICAM-1: <1.2%.</p

ABI inventoried Taqman® gene expression assays.

<p>ABI inventoried Taqman® gene expression assays and the respective ABI ID numbers.</p