The seventh national communication of Malta under the United Nations framework convention on climate change

This is the fourth time that Malta is submitting a National Communication under the United Nations Framework Convention on Climate Change (UNFCCC), following the submission of a First National Communication in 2004 and a Second National Communication in 2010. This is also the second time that Malta is submitting such a Communication since its accession to Annex I status under the Convention, the first two submissions having been made as a non-Annex I Party. Emission reduction or limitation commitments applicable to Malta Malta’s status under the Convention up to the time it applied for accession to Annex I, and with that accession being conditional to not taking on quantified emission limitation or reduction targets for the first commitment period of the Kyoto Protocol, meant that until 2012 Malta was not subject to an economy-wide greenhouse gas related obligation under the Protocol. This however did not mean that Malta had no obligations to limit or reduce emissions from anthropogenic activities taking place in the country. In line with, Malta will be contributing its fair share of the EU’s unconditional commitment under the Convention to reduce emissions by 20% below 1990 levels by 2020. This is in line with the target inscribed in the amendments to the Kyoto Protocol (the Doha Amendments), that will be jointly fulfilling the second commitment period with the other Union member states; therefore, emissions from the aforementioned power plants remain subject to compliance with EU Emissions Trading Scheme provisions, while the Effort-Sharing Decision target is the principal emissions mitigation obligation that the country has until 2020, for all other greenhouse gas emissions. The major point sources of greenhouse gas emissions in Malta, namely the electricity generation plants have been, since of 2005, subject to the EU Emissions Trading Scheme, whereby they are required to surrender allowances in respect of emissions of carbon dioxide. Emissions of greenhouse gases not covered by the EU Emissions Trading Scheme, are subject to an overall limit under the so-called Effort-Sharing Decision. Under this decision, Malta must limit such greenhouse gases to not more than 5% over emission levels in 2005, by 2020. The EU is already looking towards the longer-term future, with the 2030 climate and energy framework providing for a 40% domestic reduction target for 2030. Legislative implementation of this goal is currently under discussion at EU level.peer-reviewe

Frequency drift in MR spectroscopy at 3T

Purpose: Heating of gradient coils and passive shim components is a common cause of instability in the B-0 field, especially when gradient intensive sequences are used. The aim of the study was to set a benchmark for typical drift encountered during MR spectroscopy (MRS) to assess the need for real-time field-frequency locking on MRI scanners by comparing field drift data from a large number of sites.Method: A standardized protocol was developed for 80 participating sites using 99 3T MR scanners from 3 major vendors. Phantom water signals were acquired before and after an EPI sequence. The protocol consisted of: minimal preparatory imaging; a short pre-fMRI PRESS; a ten-minute fMRI acquisition; and a long post-fMRI PRESS acquisition. Both pre- and post-fMRI PRESS were non-water suppressed. Real-time frequency stabilization/adjustment was switched off when appropriate. Sixty scanners repeated the protocol for a second dataset. In addition, a three-hour post-fMRI MRS acquisition was performed at one site to observe change of gradient temperature and drift rate. Spectral analysis was performed using MATLAB. Frequency drift in pre-fMRI PRESS data were compared with the first 5:20 minutes and the full 30:00 minutes of data after fMRI. Median (interquartile range) drifts were measured and showed in violin plot. Paired t-tests were performed to compare frequency drift pre- and post-fMRI. A simulated in vivo spectrum was generated using FID-A to visualize the effect of the observed frequency drifts. The simulated spectrum was convolved with the frequency trace for the most extreme cases. Impacts of frequency drifts on NAA and GABA were also simulated as a function of linear drift. Data from the repeated protocol were compared with the corresponding first dataset using Pearson's and intraclass correlation coefficients (ICC).Results: Of the data collected from 99 scanners, 4 were excluded due to various reasons. Thus, data from 95 scanners were ultimately analyzed. For the first 5:20 min (64 transients), median (interquartile range) drift was 0.44 (1.29) Hz before fMRI and 0.83 (1.29) Hz after. This increased to 3.15 (4.02) Hz for the full 30 min (360 transients) run. Average drift rates were 0.29 Hz/min before fMRI and 0.43 Hz/min after. Paired t-tests indicated that drift increased after fMRI, as expected (p &lt; 0.05). Simulated spectra convolved with the frequency drift showed that the intensity of the NAA singlet was reduced by up to 26%, 44 % and 18% for GE, Philips and Siemens scanners after fMRI, respectively. ICCs indicated good agreement between datasets acquired on separate days. The single site long acquisition showed drift rate was reduced to 0.03 Hz/min approximately three hours after fMRI.Discussion: This study analyzed frequency drift data from 95 3T MRI scanners. Median levels of drift were relatively low (5-min average under 1 Hz), but the most extreme cases suffered from higher levels of drift. The extent of drift varied across scanners which both linear and nonlinear drifts were observed.</p

Possible role of circulating bone marrow mesenchymal progenitors in modulating inflammation and promoting wound repair

Circulating bone marrow mesenchymal progenitors (BMMPs) are known to be potent antigen-presenting cells that migrate to damaged tissue to secrete cytokines and growth factors. An altered or dysregulated inflammatory cascade leads to a poor healing outcome. A skin model developed in our previous study was used to observe the immuno-modulatory properties of circulating BMMP cells in inflammatory chronic wounds in a scenario of low skin perfusion. BMMPs were analysed exclusively and in conjunction with recombinant tumour necrosis factor alpha (TNF) and recombinant hepatocyte growth factor (HGF) supplementation. We analysed the expression levels of interleukin-8 (IL-8) and ecto-50-nucleotidase (CD73), together with protein levels for IL-8, stem cell factor (SCF), and fibroblast growth factor 1 (FGF-1). The successfully isolated BMMPs were positive for both hemopoietic and mesenchymal markers and showed the ability to differentiate into adipocytes, chondrocytes, and osteocytes. Significant differences were found in IL-8 and CD73 expressions and IL-8 and SCF concentrations, for all conditions studied over the three time points taken into consideration. Our data suggests that BMMPs may modulate the inflammatory response by regulating IL-8 and CD73 and influencing IL-8 and SCF protein secretions. In conclusion, we suggest that BMMPs play a role in wound repair and that their induced application might be suitable for scenarios with a low skin perfusion.peer-reviewe

HPV positivity varies with technique and primer set, in formalin-fixed paraffin-embedded benign and malignant breast tissue from Malta

The role of human papillomavirus in breast cancer pathogenesis is an area of considerable debate following differing results from all over the world. This study analyzed paraffin embedded tissue from 19 patients with benign or malignant breast disease. Standard PCR with GP5+/6+ and FAP primers, proved negative in all cases. However, qRT-PCR using the SF10 primer set detected HPV DNA in 2 out of these samples. Whilst our data does not support a major role for HPV in the pathogenesis of breast disease in Malta, it definitely does not exclude it totally. This study also clearly shows that the method of analysis is one of the variables resulting in the range of differing results witnessed worldwide in this area of study.peer-reviewe

Interobserver agreement for the ATS/ERS/JRS/ALAT criteria for a UIP pattern on CT.

OBJECTIVES: To establish the level of observer variation for the current ATS/ERS/JRS/ALAT criteria for a diagnosis of usual interstitial pneumonia (UIP) on CT among a large group of thoracic radiologists of varying levels of experience. MATERIALS AND METHODS: 112 observers (96 of whom were thoracic radiologists) categorised CTs of 150 consecutive patients with fibrotic lung disease using the ATS/ERS/JRS/ALAT CT criteria for a UIP pattern (3 categories--UIP, possibly UIP and inconsistent with UIP). The presence of honeycombing, traction bronchiectasis and emphysema was also scored using a 3-point scale (definitely present, possibly present, absent). Observer agreement for the UIP categorisation and for the 3 CT patterns in the entAUe observer group and in subgroups stratified by observer experience, were evaluated. RESULTS: Interobserver agreement across the diagnosis category scores among the 112 observers was moderate, ranging from 0.48 (IQR 0.18) for general radiologists to 0.52 (IQR 0.20) for thoracic radiologists of 10-20 years' experience. A binary score for UIP versus possible or inconsistent with UIP was examined. Observer agreement for this binary score was only moderate. No significant differences in agreement levels were identified when the CTs were stratified according to multidisciplinary team (MDT) diagnosis or patient age or when observers were categorised according to experience. Observer agreement for each of honeycombing, traction bronchiectasis and emphysema were 0.59+/-0.12, 0.42+/-0.15 and 0.43+/-0.18, respectively. CONCLUSIONS: Interobserver agreement for the current ATS/ERS/JRS/ALAT CT criteria for UIP is only moderate among thoracic radiologists, AUrespective of theAU experience, and did not vary with patient age or the MDT diagnosis

Frequency drift in MR spectroscopy at 3T.

PurposeHeating of gradient coils and passive shim components is a common cause of instability in the B0 field, especially when gradient intensive sequences are used. The aim of the study was to set a benchmark for typical drift encountered during MR spectroscopy (MRS) to assess the need for real-time field-frequency locking on MRI scanners by comparing field drift data from a large number of sites.MethodA standardized protocol was developed for 80 participating sites using 99 3T MR scanners from 3 major vendors. Phantom water signals were acquired before and after an EPI sequence. The protocol consisted of: minimal preparatory imaging; a short pre-fMRI PRESS; a ten-minute fMRI acquisition; and a long post-fMRI PRESS acquisition. Both pre- and post-fMRI PRESS were non-water suppressed. Real-time frequency stabilization/adjustment was switched off when appropriate. Sixty scanners repeated the protocol for a second dataset. In addition, a three-hour post-fMRI MRS acquisition was performed at one site to observe change of gradient temperature and drift rate. Spectral analysis was performed using MATLAB. Frequency drift in pre-fMRI PRESS data were compared with the first 5:20 minutes and the full 30:00 minutes of data after fMRI. Median (interquartile range) drifts were measured and showed in violin plot. Paired t-tests were performed to compare frequency drift pre- and post-fMRI. A simulated in vivo spectrum was generated using FID-A to visualize the effect of the observed frequency drifts. The simulated spectrum was convolved with the frequency trace for the most extreme cases. Impacts of frequency drifts on NAA and GABA were also simulated as a function of linear drift. Data from the repeated protocol were compared with the corresponding first dataset using Pearson's and intraclass correlation coefficients (ICC).ResultsOf the data collected from 99 scanners, 4 were excluded due to various reasons. Thus, data from 95 scanners were ultimately analyzed. For the first 5:20 min (64 transients), median (interquartile range) drift was 0.44 (1.29) Hz before fMRI and 0.83 (1.29) Hz after. This increased to 3.15 (4.02) Hz for the full 30 min (360 transients) run. Average drift rates were 0.29 Hz/min before fMRI and 0.43 Hz/min after. Paired t-tests indicated that drift increased after fMRI, as expected (p &lt; 0.05). Simulated spectra convolved with the frequency drift showed that the intensity of the NAA singlet was reduced by up to 26%, 44 % and 18% for GE, Philips and Siemens scanners after fMRI, respectively. ICCs indicated good agreement between datasets acquired on separate days. The single site long acquisition showed drift rate was reduced to 0.03 Hz/min approximately three hours after fMRI.DiscussionThis study analyzed frequency drift data from 95 3T MRI scanners. Median levels of drift were relatively low (5-min average under 1 Hz), but the most extreme cases suffered from higher levels of drift. The extent of drift varied across scanners which both linear and nonlinear drifts were observed

Long-term safety and efficacy of emtricitabine and tenofovir alafenamide vs emtricitabine and tenofovir disoproxil fumarate for HIV-1 pre-exposure prophylaxis: week 96 results from a randomised, double-blind, placebo-controlled, phase 3 trial

In DISCOVER, a multinational, randomised controlled trial, emtricitabine and tenofovir alafenamide compared with emtricitabine and tenofovir disoproxil fumarate showed non-inferior efficacy for HIV prevention and improved bone mineral density and renal safety biomarkers at week 48. We report outcomes analysed after all participants had completed 96 weeks of follow-up. This study is an ongoing, randomised, double-blind, multicentre, active-controlled, phase 3, non-inferiority trial done at 94 community, public health, and hospital-associated clinics located in Europe and North America. Adult cisgender men and transgender women who have sex with men, both with a high risk of acquiring HIV as determined by self-reported sexual behaviour or recent sexually transmitted infections, were randomly assigned (1:1) to receive either emtricitabine and tenofovir alafenamide (200/25 mg) tablets daily, with matched placebo tablets (emtricitabine and tenofovir alafenamide group), or emtricitabine and tenofovir disoproxil fumarate (200/300 mg) tablets daily, with matched placebo tablets (emtricitabine and tenofovir disoproxil fumarate group). The primary efficacy outcome was incident HIV infection. Incidence of HIV-1 infection per 100 person-years was assessed when the last participant had completed 96 weeks of follow-up. This trial is registered with ClinicalTrials.gov, number NCT02842086. Between Sept 13, 2016, and June 30, 2017, 5387 participants were randomly assigned to receive emtricitabine and tenofovir alafenamide (n=2694) or emtricitabine and tenofovir disoproxil fumarate (n=2693), contributing 10 081 person-years of follow-up. At 96 weeks of follow-up, there were eight HIV infections in participants who had received emtricitabine and tenofovir alafenamide (0·16 infections per 100 person-years [95% CI 0·07–0·31]) and 15 in participants who had received emtricitabine and tenofovir disoproxil fumarate (0·30 infections per 100 person-years [0·17–0·49]). Emtricitabine and tenofovir alafenamide maintained its non-inferiority to emtricitabine and tenofovir disoproxil fumarate for HIV prevention (IRR 0·54 [95% CI 0·23–1·26]). Approximately 78–82% of participants reported taking study medication more than 95% of the time across all study visits. Rates of sexually transmitted infections remained high and similar across groups (21 cases per 100 person-years for rectal gonorrhoea and 28 cases per 100 person-years for rectal chlamydia). Emtricitabine and tenofovir alafenamide continued to show superiority over emtricitabine and tenofovir disoproxil fumarate in all but one of the six prespecified bone mineral density and renal biomarkers. There was more weight gain among participants who had received emtricitabine and tenofovir alafenamide (median weight gain 1·7 kg vs 0·5 kg, p<0·0001). Emtricitabine and tenofovir alafenamide is safe and effective for longer-term pre-exposure prophylaxis in cisgender men and transgender women who have sex with men. Gilead Sciences

Cerebral microbleeds and stroke risk after ischaemic stroke or transient ischaemic attack:a pooled analysis of individual patient data from cohort studies

BACKGROUND Cerebral microbleeds are a neuroimaging biomarker of stroke risk. A crucial clinical question is whether cerebral microbleeds indicate patients with recent ischaemic stroke or transient ischaemic attack in whom the rate of future intracranial haemorrhage is likely to exceed that of recurrent ischaemic stroke when treated with antithrombotic drugs. We therefore aimed to establish whether a large burden of cerebral microbleeds or particular anatomical patterns of cerebral microbleeds can identify ischaemic stroke or transient ischaemic attack patients at higher absolute risk of intracranial haemorrhage than ischaemic stroke. METHODS We did a pooled analysis of individual patient data from cohort studies in adults with recent ischaemic stroke or transient ischaemic attack. Cohorts were eligible for inclusion if they prospectively recruited adult participants with ischaemic stroke or transient ischaemic attack; included at least 50 participants; collected data on stroke events over at least 3 months follow-up; used an appropriate MRI sequence that is sensitive to magnetic susceptibility; and documented the number and anatomical distribution of cerebral microbleeds reliably using consensus criteria and validated scales. Our prespecified primary outcomes were a composite of any symptomatic intracranial haemorrhage or ischaemic stroke, symptomatic intracranial haemorrhage, and symptomatic ischaemic stroke. We registered this study with the PROSPERO international prospective register of systematic reviews, number CRD42016036602. FINDINGS Between Jan 1, 1996, and Dec 1, 2018, we identified 344 studies. After exclusions for ineligibility or declined requests for inclusion, 20 322 patients from 38 cohorts (over 35 225 patient-years of follow-up; median 1·34 years [IQR 0·19-2·44]) were included in our analyses. The adjusted hazard ratio [aHR] comparing patients with cerebral microbleeds to those without was 1·35 (95% CI 1·20-1·50) for the composite outcome of intracranial haemorrhage and ischaemic stroke; 2·45 (1·82-3·29) for intracranial haemorrhage and 1·23 (1·08-1·40) for ischaemic stroke. The aHR increased with increasing cerebral microbleed burden for intracranial haemorrhage but this effect was less marked for ischaemic stroke (for five or more cerebral microbleeds, aHR 4·55 [95% CI 3·08-6·72] for intracranial haemorrhage vs 1·47 [1·19-1·80] for ischaemic stroke; for ten or more cerebral microbleeds, aHR 5·52 [3·36-9·05] vs 1·43 [1·07-1·91]; and for ≥20 cerebral microbleeds, aHR 8·61 [4·69-15·81] vs 1·86 [1·23-1·82]). However, irrespective of cerebral microbleed anatomical distribution or burden, the rate of ischaemic stroke exceeded that of intracranial haemorrhage (for ten or more cerebral microbleeds, 64 ischaemic strokes [95% CI 48-84] per 1000 patient-years vs 27 intracranial haemorrhages [17-41] per 1000 patient-years; and for ≥20 cerebral microbleeds, 73 ischaemic strokes [46-108] per 1000 patient-years vs 39 intracranial haemorrhages [21-67] per 1000 patient-years). INTERPRETATION In patients with recent ischaemic stroke or transient ischaemic attack, cerebral microbleeds are associated with a greater relative hazard (aHR) for subsequent intracranial haemorrhage than for ischaemic stroke, but the absolute risk of ischaemic stroke is higher than that of intracranial haemorrhage, regardless of cerebral microbleed presence, antomical distribution, or burden. FUNDING British Heart Foundation and UK Stroke Association

Frequency drift in MR spectroscopy at 3T

Purpose: Heating of gradient coils and passive shim components is a common cause of instability in the B-0 field, especially when gradient intensive sequences are used. The aim of the study was to set a benchmark for typical drift encountered during MR spectroscopy (MRS) to assess the need for real-time field-frequency locking on MRI scanners by comparing field drift data from a large number of sites. Method: A standardized protocol was developed for 80 participating sites using 99 3T MR scanners from 3 major vendors. Phantom water signals were acquired before and after an EPI sequence. The protocol consisted of: minimal preparatory imaging; a short pre-fMRI PRESS; a ten-minute fMRI acquisition; and a long post-fMRI PRESS acquisition. Both pre- and post-fMRI PRESS were non-water suppressed. Real-time frequency stabilization/adjustment was switched off when appropriate. Sixty scanners repeated the protocol for a second dataset. In addition, a three-hour post-fMRI MRS acquisition was performed at one site to observe change of gradient temperature and drift rate. Spectral analysis was performed using MATLAB. Frequency drift in pre-fMRI PRESS data were compared with the first 5:20 minutes and the full 30:00 minutes of data after fMRI. Median (interquartile range) drifts were measured and showed in violin plot. Paired t-tests were performed to compare frequency drift pre- and post-fMRI. A simulated in vivo spectrum was generated using FID-A to visualize the effect of the observed frequency drifts. The simulated spectrum was convolved with the frequency trace for the most extreme cases. Impacts of frequency drifts on NAA and GABA were also simulated as a function of linear drift. Data from the repeated protocol were compared with the corresponding first dataset using Pearson's and intraclass correlation coefficients (ICC). Results: Of the data collected from 99 scanners, 4 were excluded due to various reasons. Thus, data from 95 scanners were ultimately analyzed. For the first 5:20 min (64 transients), median (interquartile range) drift was 0.44 (1.29) Hz before fMRI and 0.83 (1.29) Hz after. This increased to 3.15 (4.02) Hz for the full 30 min (360 transients) run. Average drift rates were 0.29 Hz/min before fMRI and 0.43 Hz/min after. Paired t-tests indicated that drift increased after fMRI, as expected (p < 0.05). Simulated spectra convolved with the frequency drift showed that the intensity of the NAA singlet was reduced by up to 26%, 44 % and 18% for GE, Philips and Siemens scanners after fMRI, respectively. ICCs indicated good agreement between datasets acquired on separate days. The single site long acquisition showed drift rate was reduced to 0.03 Hz/min approximately three hours after fMRI. Discussion: This study analyzed frequency drift data from 95 3T MRI scanners. Median levels of drift were relatively low (5-min average under 1 Hz), but the most extreme cases suffered from higher levels of drift. The extent of drift varied across scanners which both linear and nonlinear drifts were observed