Air conditioning production by a single effect absorption cooling machine directly coupled to a solar collector field. Application to Spanish climates

Due to the increasing energy consumption of air conditioning in buildings and the need to decrease the fossil CO2 emissions to the environment, the interest of using renewable energy sources shows up stronger than ever. We present a general study whose aim is to propose a method to evaluate an upper bound in the potential of solar cooling by using some simplified models. As an example it has been applied to the very diverse climates of Spain. In the paper it has been assumed a direct solar coupling between the solar collector field and a single effect absorption cooling machine, without any intermediate solar storage tank. An equation is obtained that shows the dependence of the generator/solar-collectors equilibrium temperature on basic design parameters of the system (absorption machine-solar collectors). The paper analyzes the effect of these on the total amount of cooling produced along a typical mean year and the peak cooling power. The paper also includes a discussion on how to estimate the values and what is their physical meaning of the parameters which define the behavior of real absorption machines. Finally tables are included for the 12 climates of Spain that can be used as an example of how to make a quick pre-sizing of such direct coupled system. The classification of the Spanish climates is based on general data (average monthly total horizontal solar radiation, average monthly dry temperature, etc.) and the results could be generalized for climates with the same severity. Moreover if hourly weather data is available for any place (like tmy2, bin, epw, etc. files), the procedure can be applied without further changes.Sarabia Escrivà, EJ.; Lamas Sivila, EV.; Soto Francés, VM. (2011). Air conditioning production by a single effect absorption cooling machine directly coupled to a solar collector field. Application to Spanish climates. Solar Energy. 85(9):2108-2121. doi:10.1016/j.solener.2011.05.019S2108212185

Transcriptional diversity during lineage commitment of human blood progenitors.

Blood cells derive from hematopoietic stem cells through stepwise fating events. To characterize gene expression programs driving lineage choice, we sequenced RNA from eight primary human hematopoietic progenitor populations representing the major myeloid commitment stages and the main lymphoid stage. We identified extensive cell type-specific expression changes: 6711 genes and 10,724 transcripts, enriched in non-protein-coding elements at early stages of differentiation. In addition, we found 7881 novel splice junctions and 2301 differentially used alternative splicing events, enriched in genes involved in regulatory processes. We demonstrated experimentally cell-specific isoform usage, identifying nuclear factor I/B (NFIB) as a regulator of megakaryocyte maturation-the platelet precursor. Our data highlight the complexity of fating events in closely related progenitor populations, the understanding of which is essential for the advancement of transplantation and regenerative medicine.The work described in this article was primarily supported by the European Commission Seventh Framework Program through the BLUEPRINT grant with code HEALTH-F5-2011-282510 (D.H., F.B., G.C., J.H.A.M., K.D., L.C., M.F., S.C., S.F., and S.P.G.). Research in the Ouwehand laboratory is further supported by program grants from the National Institute for Health Research (NIHR, www.nihr.ac.uk; to A.A., M.K., P.P., S.B.G.J., S.N., and W.H.O.) and the British Heart Foundation under nos. RP-PG-0310-1002 and RG/09/12/28096 (www.bhf.org.uk; to A.R. and W.J.A.). K.F. and M.K. were supported by Marie Curie funding from the NETSIM FP7 program funded by the European Commission. The laboratory receives funding from the NHS Blood and Transplant for facilities. The Cambridge BioResource (www.cambridgebioresource.org.uk), the Cell Phenotyping Hub, and the Cambridge Translational GenOmics laboratory (www.catgo.org.uk) are supported by an NIHR grant to the Cambridge NIHR Biomedical Research Centre (BRC). The BRIDGE-Bleeding and Platelet Disorders Consortium is supported by the NIHR BioResource—Rare Diseases (http://bioresource.nihr.ac.uk/; to E.T., N.F., and Whole Exome Sequencing effort). Research in the Soranzo laboratory (L.V., N.S., and S. Watt) is further supported by the Wellcome Trust (Grant Codes WT098051 and WT091310) and the EU FP7 EPIGENESYS initiative (Grant Code 257082). Research in the Cvejic laboratory (A. Cvejic and C.L.) is funded by the Cancer Research UK under grant no. C45041/A14953. S.J.S. is funded by NIHR. M.E.F. is supported by a British Heart Foundation Clinical Research Training Fellowship, no. FS/12/27/29405. E.B.-M. is supported by a Wellcome Trust grant, no. 084183/Z/07/Z. Research in the Laffan laboratory is supported by Imperial College BRC. F.A.C., C.L., and S. Westbury are supported by Medical Research Council Clinical Training Fellowships, and T.B. by a British Society of Haematology/NHS Blood and Transplant grant. R.J.R. is a Principal Research Fellow of the Wellcome Trust, grant no. 082961/Z/07/Z. Research in the Flicek laboratory is also supported by the Wellcome Trust (grant no. 095908) and EMBL. Research in the Bertone laboratory is supported by EMBL. K.F. and C.v.G. are supported by FWO-Vlaanderen through grant G.0B17.13N. P.F. is a compensated member of the Omicia Inc. Scientific Advisory Board. This study made use of data generated by the UK10K Consortium, derived from samples from the Cohorts arm of the project.This is the author’s version of the work. It is posted here by permission of the AAAS for personal use, not for redistribution. The definitive version was published in Science on 26/9/14 in volume 345, number 6204, DOI: 10.1126/science.1251033. This version will be under embargo until the 26th of March 2015

Comparison of different sources of platelet-rich plasma as treatment option for infertility-causing endometrial pathologies

Objective. To study the effect of human plasma from different sources such as umbilical cord blood and adult blood platelet-rich plasma (PRP) on the regeneration of endometrial damage. Design. Composition analysis, in vitro approaches and a pre-clinical murine model using plasma to promote endometrial regeneration. Setting. Hospital and university laboratories. Patients/Animals. Adult plasma from 4 Atrophy patients and one fertile woman, commercial umbilical cord plasma and uterine-damaged NOD/SCID mice model were used. Intervention(s). Endometrial stromal cells from primary culture and an endometrial stem cell line were cultured in vitro and uterine-damaged NOD/SCID mice were treated with plasma samples from several origins. Main Outcome Measure(s). All plasma samples contain molecules with a high potential for regeneration (SCF, PDGFBB, THBS1, VWF). Furthermore, the highest increase in in vitro proliferation and migration rate was found when endometrial stromal cells were treated with umbilical cord plasma, adult PRP also revealed a significant increment. In the mouse model, a higher expression of Ki67 and Hoxa10 in the endometrium was detected after applying adult PRP and the proteomic analysis revealed a specific protein expression profile depending on the treatment. The damaged uterine tissue showed more pro22 regenerative markers after applying umbilical cord plasma (Stat5a, Uba3, Thy1) in comparison to the other treatments (non-activated umbilical cord plasma, activated adult PRP and not treatment). Conclusion. Human PRP possesses regeneration properties usable for endometrial pathologies. Besides that, these regenerative effects seem to be more apparent when the source of obtaining is umbilical cord blood

Spondylarthropathies (including psoriatic arthritis): 244. Validity of Colour Doppler and Spectral Doppler Ultrasound of Sacroilicac Joints Againts Physical Examination as Gold Standard

Background: Sacroiliac joints (SJ) involvement is a distinctive and charasteristic feature of Spondyloarthritis (SpA) and x-ray is the test routinely used to make a diagnosis. However, x-ray reveals late structural damage but cannot detect active inflammation. The objective of this study was to assess the validity of Doppler ultrasound in SJ. Methods: Prospective blinded and controlled study of SJ, in which three populations were compared. We studied 106 consecutive cases, who were divided into three groups: a) 53 patients diagnosed with SpA who had inflammatory lumbar and gluteal pain assessed by a rheumatologist; b) 26 patients diagnosed with SpA who didn't have SJ tenderness and had normal physical examination; c) control group of 27 subjects (healthy subjetcs or with mechanical lumbar pain). All patients included that were diagnosed with SpA met almost the European Spondyloarthropathy Study Group (ESSG) classification criteria. Physical examination of the SJ included: sacral sulcus tenderness, iliac gapping, iliac compression, midline sacral thrust test, Gaenslen's test, and Patrick s test were used as gold standard. Both SJ were examined with Doppler ultrasound (General Electric Logiq 9, Wauwatosa WI, USA) fitted with a 9-14 Mhz lineal probe. The ultrasonographer was blinded to clinical data. Doppler in SJ was assessed as positive when both Doppler colour and resistance index (RI) < 0.75 within the SJ area were present. Statistical analysis was performed estimating sensitivity and specificity against gold standard. The Kappa correlation coefficient was used for reliability study. Results: 106 cases (53 female, 55 male; mean age 36 10 years) were studied. There were no statistical differences between groups related to age or sex. Physical examination of SJ was positive in 38 patients (59 sacroiliac joints). US detected Doppler signal within SJ in 37 patients (58 SJ): 33 of them were symptomatic SpA (52 SJ), one of them were asymptomatic SpA (1 SJ) and one was a healthy control (1 SJ). The accuracy of US when compared to clinical data as gold standard at subject level in the overall group was: sensitivity of 68.6% and specificity of 85.7%, positive predictive value of 70.5% and negative predictive value of 84.5%. A positive likelihood ratio of 4.8, a negative likelihood ratio of 0.36 and a kappa coefficient of 0.55 were achieved. Conclusions: Doppler US of SJ seems to be a valid method to detect active SJ inflammation. Disclosure statement: The authors have declared no conflicts of interes

Pharmacological profiling of small molecule modulators of the TMEM16A channel and their implications for the control of artery and capillary function

Background and purpose: TMEM16A chloride channels constitute a depolarising mechanism in arterial smooth muscle cells (SMCs) and contractile cerebral pericytes. TMEM16A pharmacology is incompletely defined. We elucidated the mode of action and selectivity of a recently identified positive allosteric modulator of TMEM16A (PAM_16A) and of a range of TMEM16A inhibitors. We also explore the consequences of selective modulation of TMEM16A activity on arterial and capillary function. Experimental approach: Patch‐clamp electrophysiology, isometric tension recordings, live imaging of cerebral cortical capillaries and assessment of cell death were employed to explore the effect of selective pharmacological control of TMEM16A on vascular function. Key Results: In low intracellular free Ca2+ concentrations ([Ca2+]i), nanomolar concentrations of PAM_16A activated heterologous TMEM16A channels, while being almost ineffective on the closely related TMEM16B channel. In either the absence of Ca2+ or in saturating [Ca2+]i, PAM_16A had no effect on TMEM16A currents at physiological potentials. PAM_16A selectively activated TMEM16A currents in SMCs and enhanced aortic contraction caused by phenylephrine or angiotensin‐II and capillary (pericyte) constriction evoked by endothelin‐1 or oxygen–glucose deprivation (OGD) to simulate cerebral ischaemia. Conversely, selective TMEM16A inhibition with Ani9 facilitated aortic, mesenteric and pericyte relaxation, and protected against OGD‐mediated pericyte cell death. Unlike PAM_16A and Ani9, a range of other available modulators were found to interfere with endogenous cationic currents in SMCs. Conclusions and implications: Arterial tone and capillary diameter can be controlled with TMEM16A modulators, highlighting TMEM16A as a target for disorders with a vascular component, including hypertension, stroke, Alzheimer's disease and vascular dementia

Case Reports1. A Late Presentation of Loeys-Dietz Syndrome: Beware of TGFβ Receptor Mutations in Benign Joint Hypermobility

Background: Thoracic aortic aneurysms (TAA) and dissections are not uncommon causes of sudden death in young adults. Loeys-Dietz syndrome (LDS) is a rare, recently described, autosomal dominant, connective tissue disease characterized by aggressive arterial aneurysms, resulting from mutations in the transforming growth factor beta (TGFβ) receptor genes TGFBR1 and TGFBR2. Mean age at death is 26.1 years, most often due to aortic dissection. We report an unusually late presentation of LDS, diagnosed following elective surgery in a female with a long history of joint hypermobility. Methods: A 51-year-old Caucasian lady complained of chest pain and headache following a dural leak from spinal anaesthesia for an elective ankle arthroscopy. CT scan and echocardiography demonstrated a dilated aortic root and significant aortic regurgitation. MRA demonstrated aortic tortuosity, an infrarenal aortic aneurysm and aneurysms in the left renal and right internal mammary arteries. She underwent aortic root repair and aortic valve replacement. She had a background of long-standing joint pains secondary to hypermobility, easy bruising, unusual fracture susceptibility and mild bronchiectasis. She had one healthy child age 32, after which she suffered a uterine prolapse. Examination revealed mild Marfanoid features. Uvula, skin and ophthalmological examination was normal. Results: Fibrillin-1 testing for Marfan syndrome (MFS) was negative. Detection of a c.1270G > C (p.Gly424Arg) TGFBR2 mutation confirmed the diagnosis of LDS. Losartan was started for vascular protection. Conclusions: LDS is a severe inherited vasculopathy that usually presents in childhood. It is characterized by aortic root dilatation and ascending aneurysms. There is a higher risk of aortic dissection compared with MFS. Clinical features overlap with MFS and Ehlers Danlos syndrome Type IV, but differentiating dysmorphogenic features include ocular hypertelorism, bifid uvula and cleft palate. Echocardiography and MRA or CT scanning from head to pelvis is recommended to establish the extent of vascular involvement. Management involves early surgical intervention, including early valve-sparing aortic root replacement, genetic counselling and close monitoring in pregnancy. Despite being caused by loss of function mutations in either TGFβ receptor, paradoxical activation of TGFβ signalling is seen, suggesting that TGFβ antagonism may confer disease modifying effects similar to those observed in MFS. TGFβ antagonism can be achieved with angiotensin antagonists, such as Losartan, which is able to delay aortic aneurysm development in preclinical models and in patients with MFS. Our case emphasizes the importance of timely recognition of vasculopathy syndromes in patients with hypermobility and the need for early surgical intervention. It also highlights their heterogeneity and the potential for late presentation. Disclosures: The authors have declared no conflicts of interes

Remission outcomes in severe eosinophilic asthma with mepolizumab therapy: Analysis of the REDES study

IntroductionClinical remission as a multicomponent treatment goal in severe asthma is being explored in clinical practice. This post hoc analysis used data from the REDES study to assess the proportion of patients with severe eosinophilic asthma achieving our multicomponent definitions of clinical remission after 1 year of mepolizumab treatment.MethodsThe real-world, retrospective observational REDES study enrolled patients with severe eosinophilic asthma who were newly prescribed mepolizumab and with ≥12 months of medical records pre-enrolment. Multicomponent clinical remission was defined as: oral corticosteroid (OCS)-free; exacerbation-free; asthma control test (ACT) score ≥20; and with or without post-bronchodilator forced expiratory volume in 1 second ≥80%. Baseline characteristics were also assessed in those who did/did not achieve clinical remission.Results37% and 30% of patients with severe eosinophilic asthma met our proposed three- and four-component on-treatment clinical remission definitions; an increase from 2% and 3% at baseline. Most frequently achieved individual components of clinical remission were: OCS-free; ACT score ≥20. For patients fulfilling the multicomponent clinical remission definitions, at baseline we observed higher blood eosinophil counts, better ACT scores and lung function, lower maintenance OCS use, and a slightly lower rate of prior exacerbations versus those who did not.DiscussionClinical remission is a realistic target in clinical practice for a subset of patients with severe eosinophilic asthma receiving mepolizumab. Further studies are required to elucidate whether features linked to the underlying endotype can help predict treatment outcomes, increase rates of clinical remission, and potentially modify disease progression

Resting-state fMRI seizure onset localization meta-analysis: comparing rs-fMRI to other modalities including surgical outcomes

ObjectiveResting-state functional MRI (rs-fMRI) may localize the seizure onset zone (SOZ) for epilepsy surgery, when compared to intracranial EEG and surgical outcomes, per a prior meta-analysis. Our goals were to further characterize this agreement, by broadening the queried rs-fMRI analysis subtypes, comparative modalities, and same-modality comparisons, hypothesizing SOZ-signal strength may overcome this heterogeneity.MethodsPubMed, Embase, Scopus, Web of Science, and Google Scholar between April 2010 and April 2020 via PRISMA guidelines for SOZ-to-established-modalities were screened. Odd ratios measured agreement between SOZ and other modalities. Fixed- and random-effects analyses evaluated heterogeneity of odd ratios, with the former evaluating differences in agreement across modalities and same-modality studies.ResultsIn total, 9,550 of 14,384 were non-duplicative articles and 25 met inclusion criteria. Comparative modalities were EEG 7, surgical outcome 6, intracranial EEG 5, anatomical MRI 4, EEG-fMRI 2, and magnetoencephalography 1. Independent component analysis 9 and seed-based analysis 8 were top rs-fMRI methods. Study-level odds ratio heterogeneity in both the fixed- and random-effects analysis was significant (p &lt; 0.001). Marked cross-modality and same-modality systematic differences in agreement between rs-fMRI and the comparator were present (p = 0.005 and p = 0.002), respectively, with surgical outcomes having higher agreement than EEG (p = 0.002) and iEEG (p = 0.007). The estimated population mean sensitivity and specificity were 0.91 and 0.09, with predicted values across studies ranging from 0.44 to 0.96 and 0.02 to 0.67, respectively.SignificanceWe evaluated centrality and heterogeneity in SOZ agreement between rs-fMRI and comparative modalities using a wider variety of rs-fMRI analyzing subtypes and comparative modalities, compared to prior. Strong evidence for between-study differences in the agreement odds ratio was shown by both the fixed- and the random-effects analyses, attributed to rs-fMRI analysis variability. Agreement with rs-fMRI differed by modality type, with surgical outcomes having higher agreement than EEG and iEEG. Overall, sensitivity was high, but specificity was low, which may be attributed in part to differences between other modalities

What's in a Name? Shifting Identities of Traditional Organized Crime in Canada in the Transnational Fight against the Calabrian ‘Ndrangheta

The Italian antimafia authorities have warned Canadian law enforcement about the risks and the growing concerns for the infiltration of clans of the Calabrian mafia, known as ‘ndrangheta, in Eastern Canada. The alarm linked to the rise of the ‘ndrangheta challenges the paradigms of traditional organized crime in Canada, because the ‘ndrangheta is presented as traditional but also innovative and more pervasive than other mafia-type groups. Through access to confidential investigations and interviews to key specialist law enforcement teams in Toronto and Montreal, this article investigates today's institutional perception of mafia – the ‘ndrangheta in particular – in Canada when compared to Italian conceptualizations. I will argue that the changes in narratives in Canada can be read in relation to changes in the Italian identity in the country, moving towards regionalization and specialist knowledge of ethnic differences

Nrf2-interacting nutrients and COVID-19 : time for research to develop adaptation strategies

There are large between- and within-country variations in COVID-19 death rates. Some very low death rate settings such as Eastern Asia, Central Europe, the Balkans and Africa have a common feature of eating large quantities of fermented foods whose intake is associated with the activation of the Nrf2 (Nuclear factor (erythroid-derived 2)-like 2) anti-oxidant transcription factor. There are many Nrf2-interacting nutrients (berberine, curcumin, epigallocatechin gallate, genistein, quercetin, resveratrol, sulforaphane) that all act similarly to reduce insulin resistance, endothelial damage, lung injury and cytokine storm. They also act on the same mechanisms (mTOR: Mammalian target of rapamycin, PPAR gamma:Peroxisome proliferator-activated receptor, NF kappa B: Nuclear factor kappa B, ERK: Extracellular signal-regulated kinases and eIF2 alpha:Elongation initiation factor 2 alpha). They may as a result be important in mitigating the severity of COVID-19, acting through the endoplasmic reticulum stress or ACE-Angiotensin-II-AT(1)R axis (AT(1)R) pathway. Many Nrf2-interacting nutrients are also interacting with TRPA1 and/or TRPV1. Interestingly, geographical areas with very low COVID-19 mortality are those with the lowest prevalence of obesity (Sub-Saharan Africa and Asia). It is tempting to propose that Nrf2-interacting foods and nutrients can re-balance insulin resistance and have a significant effect on COVID-19 severity. It is therefore possible that the intake of these foods may restore an optimal natural balance for the Nrf2 pathway and may be of interest in the mitigation of COVID-19 severity