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Expression of CD230 upon serum-starvation in parental and trisomic cells. Representative dot plots of FSC-A vs CD230-A for HCT116 parental and HCT116 trisomic clones - 18/3 cl2 and 21/3 cl1 and 3 - cultured under normal conditions (10% FBS, control) or under serum-starvation (0% FBS) for 3 days, are shown.

Supplementary Tables S1-S3. Detailed description of antibodies used for the cell surface screenings performed with the initial 300 antibody high-throughput screening panel (S1), the 49-marker validation screening panel (S2), and the 36-marker mouse tumor screening panel (S3). Supplementary Table S4. Mean fluorescence intensity and percentage of positive cells for each surface marker staining across the cell lines initially analyzed with the MACS® Marker Screening panel. Supplementary Table S5. Mean fluorescence intensity and percentage of positive cells for the 49 surface markers selected for validation across all the cell lines, grouped according to the karyotype and normalized with the corresponding parental cells. Supplementary Tables S6. Aneuploid-to-diploid ratios obtained from previously published proteome data (7) for the proteins analyzed in this study. Supplementary Table S7. Immunophenotypic characterization of mouse models of aneuploidy (breast tumors, n=7) with a 29-marker screening panel, as well as normal mammary gland (control; n=2).

Description of the Supplementary Files

Aneuploidy is a hallmark of most human tumors, but the molecular physiology of aneuploid cells is not well characterized. In this study, we screened cell surface biomarkers of approximately 300 proteins by multiparameter flow cytometry using multiple aneuploid model systems such as cell lines, patient samples, and mouse models. Several new biomarkers were identified with altered expression in aneuploid cells, including overexpression of the cellular prion protein CD230/PrPC and the immunosuppressive cell surface enzyme ecto-5′-nucleotidase CD73. Functional analyses associated these alterations with increased cellular stress. An increased number of CD73+ cells was observed in confluent cultures in aneuploid cells relative to their diploid counterparts. An elevated expression in CD230/PrPC was observed in serum-deprived cells in association with increased generation of reactive oxygen species. Overall, our work identified biomarkers of aneuploid karyotypes, which suggest insights into the underlying molecular physiology of aneuploid cells. Cancer Res; 77(11); 2914–26. ©2017 AACR.

Honeycombing (HC) is a histological pattern consistent with Usual Interstitial Pneumonia (UIP). HC refers to cystic airways (HC airways) located at sites of dense fibrosis with marked mucus accumulation. Utilizing laser capture microdissection coupled mass spectrometry (LCM-MS), we interrogated the fibrotic HC airway cells and fibrotic uninvolved airway cells (distant from sites of UIP and morphologically intact) in 10 UIP specimens; 6 non-fibrotic airway cell specimens served as controls. Furthermore, we performed LCM-MS on the mucus plugs found in 6 UIP and 6 mucinous adenocarcinoma (MA) specimens. The mass spectrometry data were subject to both qualitative and quantitative analysis and validated by immunohistochemistry. Surprisingly, fibrotic uninvolved airway cells share a similar protein profile to HC airway cells, showing deregulation of SLITs and ROBO pathway as the strongest category. We find that BPIFB1 is the most significantly increased secretome-associated protein in UIP, whereas MUC5AC is the most significantly increased in MA. We conclude that spatial proteomics demonstrates that the fibrotic uninvolved airway cells are abnormal. In addition, fibrotic HC airway cells are enriched in mucin biogenesis proteins with a marked derangement in proteins essential for ciliogenesis. This unbiased spatial proteomic approach will generate novel and testable hypotheses to decipher fibrosis progression.

Background and Aim: Alpha-2 agonists such as dexmedetomidine when given intravenously or intrathecally as an adjuvant potentiate subarachnoid anesthesia. We studied the difference in subarachnoid anesthesia when supplemented with either intrathecal or intravenous dexmedetomidine. Material and Methods: Seventy-five patients posted for lower limb and infraumbilical procedures were enrolled for a prospective, randomized, double-blind, placebo-controlled study and divided into three groups: Group B (n = 25) received intravenous 20 mL 0.9%N aCl over 10 min followed by intrathecal 2.4 mL 0.5%bupivacaine + 0.2 mL sterile water; Group BDexIT (n = 25) received intravenous 20 mL 0.9%N aCl over 10 min followed by intrathecal 2.4 mL 0.5%b upivacaine + 0.2 mL (5 μg) dexmedetomidine; Group BDexIV (n = 25) received intravenous dexmedetomidine 1 μg/kg in 20 mL 0.9%N aCl over 10 min followed by intrathecal 2.4 mL 0.5%b upivacaine + 0.2 mL sterile water. Onset and recovery from motor and sensory blockade, and sedation score were recorded. Onset of sensory and motor blockade was assessed using Kruskal–Wallis test, whereas 2-segment regression and recovery was analyzed using ANOVA and post hoc Tukey's test to determine difference between the three groups. P value Group BDexIV > Group B (P < 0.001). Patients in Group BDexIT and Group BDexIV were sedated but easily arousable. Conclusion: Intrathecal dexmedetomidine prolongs the effect of subarachnoid anesthesia with arousable sedation when compared with intravenous dexmedetomidine.

Significance The circadian clock plays an essential role in energy metabolism and inflammation. In contrast, the importance of the clock in the pathogenesis of fibrosis remains poorly explored. This study describes a striking alteration in circadian biology during pulmonary fibrosis where the relatively arrhythmic alveolar structures gain circadian but asynchronous rhythmicity due to infiltration by fibroblasts. Disruption of the clock in these cells, which are not widely implicated in circadian pathophysiology, results in a profibrotic phenotype. Translation of these findings in humans revealed previously unrecognized important circadian risk factors for pulmonary fibrosis (sleep length, chronotype, and shift work). In addition, targeting REVERBα repressed collagen secretion from human fibrotic lung tissue, making this protein a promising therapeutic target., Pulmonary inflammatory responses lie under circadian control; however, the importance of circadian mechanisms in the underlying fibrotic phenotype is not understood. Here, we identify a striking change to these mechanisms resulting in a gain of amplitude and lack of synchrony within pulmonary fibrotic tissue. These changes result from an infiltration of mesenchymal cells, an important cell type in the pathogenesis of pulmonary fibrosis. Mutation of the core clock protein REVERBα in these cells exacerbated the development of bleomycin-induced fibrosis, whereas mutation of REVERBα in club or myeloid cells had no effect on the bleomycin phenotype. Knockdown of REVERBα revealed regulation of the little-understood transcription factor TBPL1. Both REVERBα and TBPL1 altered integrinβ1 focal-adhesion formation, resulting in increased myofibroblast activation. The translational importance of our findings was established through analysis of 2 human cohorts. In the UK Biobank, circadian strain markers (sleep length, chronotype, and shift work) are associated with pulmonary fibrosis, making them risk factors. In a separate cohort, REVERBα expression was increased in human idiopathic pulmonary fibrosis (IPF) lung tissue. Pharmacological targeting of REVERBα inhibited myofibroblast activation in IPF fibroblasts and collagen secretion in organotypic cultures from IPF patients, thus suggesting that targeting of REVERBα could be a viable therapeutic approach.

Aims Cangrelor has a potentially favorable pharmacodynamic profile in cardiogenic shock (CS). We aimed to evaluate the clinical course of CS patients undergoing percutaneous coronary intervention (PCI) treated with cangrelor. Methods and results We retrospectively identified 136 CS patients treated with cangrelor. Patients were 1:1 matched to CS patients from the IABP-SHOCK II trial not receiving cangrelor by age, sex, cardiac arrest, type of myocardial infarction, culprit lesion, glycoprotein IIb/IIIa inhibitor, and oral P2Y12-receptor inhibitor and followed-up for 12 months. The study cohort consisted of 88 matched pairs. Thirty-day and 12-month mortality was 29.5% and 34.1% in cangrelor-treated patients and 36.4% and 47.1% in control group (P = 0.34 and P = 0.08, respectively). The rate of definite acute stent thrombosis was 2.3% in both groups. Moderate and severe bleeding events occurred in 21.6% in the cangrelor and 19.3% in the control group (P = 0.71). Patients treated with cangrelor more frequently experienced ≥1 TIMI flow grade improvement during PCI (92.9% vs. 81.2%, P = 0.02). Conclusion Cangrelor treatment was associated with similar bleeding risk and significantly better TIMI flow improvement compared with oral P2Y12 inhibitors in CS patients undergoing PCI. The use of cangrelor in CS offers a potentially safe and effective antiplatelet option and should be evaluated in randomized trials.

There is a marked inclination towards cesarean sections as the preferred mode of delivery in parturients with COVID-19 disease. However, the challenges associated with planning and performing a surgery in the COVID-19 setup are considerable. These factors may lead to widespread changes in obstetric decision-making, operative planning, and perioperative outcomes. Thus, our study aimed to study the clinical and logistical factors involved in cesarean sections in COVID-19 parturients.This was a retrospective observational study performed at a dedicated COVID-19 tertiary care center in India. All women undergoing cesarean section in the specially earmarked operating room between 1A total of 44 women underwent cesarean section during the study period, with elective and emergency surgeries numbering 22 each. No indication, apart from COVID-19 status, was listed in over one-fourth of the women (13/44). The most common preoperative comorbidity was hypothyroidism (12/44). Median surgical duration was 117.5 min (IQR 100-133), with a median of 7.5 (IQR 6-8.25) healthcare personnel in the OT. Over one-fourth (12/44) of the delivered babies had low birth weight, while 4.5% (2/44) tested positive for SARS-CoV-2.COVID-19 status alone continues to be a common indication for cesarean section. Operative time is increased, but the number of healthcare personnel involved can be trimmed with proper planning. Maternal and fetal outcomes are largely positive, with low transmission rates, but a considerable proportion of low-birth-weight neonates.

ObjectivesThis study sought to determine the absolute and relative associations of diabetes mellitus (DM) and hemoglobin A1c (HbA1c) with sudden and/or arrhythmic death (SAD) versus other modes of death in patients with coronary artery disease (CAD) who do not qualify for implantable cardioverter-defibrillators.BackgroundPatients with CAD and DM are at elevated risk for SAD; however, it is unclear whether these patients would benefit from implantable cardioverter-defibrillators given competing causes of death and/or whether HbA1c might augment SAD risk stratification.MethodsIn the PRE-DETERMINE study of 5,764 patients with CAD with left ventricular ejection fraction (LVEF) of >30% to 35%, competing risk analyses were used to compare the absolute and relative risks of SAD versus non-SAD by DM status and HbA1c level and to identify risk factors for SAD among 1,782 patients with DM.ResultsOver a median follow-up of 6.8 years, DM and HbA1c were significantly associated with SAD and non-SAD (P30% to 35%, patients with DM and/or elevated HbA1c are at much higher absolute risk of dying from non-SAD than SAD. Clinical risk markers, and not HbA1c, were associated with SAD risk in patients with DM. (PRE-DETERMINE: Biologic Markers and MRI SCD Cohort Study; NCT01114269).

Background A proposed cause of dyspnea induced by ticagrelor is an increase in adenosine blood levels. Because caffeine is an adenosine antagonist, it can potentially improve drug tolerability with regard to dyspnea. Furthermore, association between caffeine and cardiovascular events is of clinical interest. Methods and Results This prespecified analysis used data from the PEGASUS TIMI 54 (Prevention of Cardiovascular Events in Patients With Prior Heart Attack Using Ticagrelor Compared to Placebo on a Background of Aspirin–Thrombolysis in Myocardial Infarction 54) trial, which randomized 21 162 patients with prior myocardial infarction to ticagrelor 60 mg or 90 mg or matching placebo (twice daily). Baseline caffeine intake in cups per week was prospectively collected for 9694 patients. Outcomes of interest included dyspnea, major adverse cardiovascular events (ie, the composite of cardiovascular death, myocardial infarction, or stroke), and arrhythmias. Dyspnea analyses considered the pooled ticagrelor group, whereas cardiovascular outcome analyses included patients from the 3 randomized arms. After adjustment, caffeine intake, compared with no intake, was not associated with lower rates of dyspnea in patients taking ticagrelor (adjusted hazard ratio (HR), 0.91; 95% CI , 0.76–1.10; P =0.34). There was no excess risk with caffeine for major adverse cardiovascular events (adjusted HR, 0.78; 95% CI, 0.63–0.98; P =0.031), sudden cardiac death (adjusted HR, 0.98; 95% CI, 0.57–1.70; P =0.95), or atrial fibrillation (adjusted odds ratio, 1.07; 95% CI, 0.56–2.04; P =0.84). Conclusions In patients taking ticagrelor for secondary prevention after myocardial infarction, caffeine intake at baseline was not associated with lower rates of dyspnea compared with no intake. Otherwise, caffeine appeared to be safe in this population, with no apparent increase in atherothrombotic events or clinically significant arrhythmias. Registration URL : https://www.clini​caltr​ials.gov ; Unique identifier: NCT 01225562.

In this paper, a survey of 180 inscriptions in Tamil between 1346 CE and 1400 CE is analysed for its notions and visualization of astral themes present in the epigraphical inscriptions as well as for the calendrical practices implicit in those inscriptions. I demonstrate the rich diversity of calendrical practices employed in this period. Although there are clear local usages, the applied methods of identification show that in several cases methods from other Indian calendrical traditions have also been used. This applies both to the year and the month. In contrast, the use of the weekday is not widely seen in the inscriptions of this region following the local system. The study also clarifies that the inscriptions are a useful documentary source for other astronomical observations such as eclipses and solstices undertaken in southern Indian locations in the fourteenth and fifteenth centuries.

Objectives This analysis sought to systematically characterize trial-level patterns in atrial fibrillation/atrial flutter (AF/AFL) by using the ClinicalTrials.gov database. Background Despite an abundance of clinical trials in this field, there is a lack of high-level evidence guiding management of AF/AFL. Methods We queried all closed, phase II to IV interventional trials registered in the ClinicalTrials.gov database through October 2016 that enrolled patients known to have AF/AFL. Published trials were evaluated for methodological quality, using the 3-item Jadad scale (range: 0 to 5, where 5 = highest quality). Results The initial search yielded 465 uniquely registered studies, of which 348 directly studied AF/AFL. Of those studies, 173 (50%) were published, enrolling a median of 190 patients from a median of 15 sites. The volume of published trials increased over time (7% prior to 2008 vs. 41% from 2014 to 2016; p Conclusions Contemporary trials of AF/AFL are often multicenter and modest in size. The primary study endpoint is commonly recurrence of arrhythmia, even in high-quality and late-phase trials. Although methodological quality is high in trials of pharmacologic approaches, trials of AF/AFL ablation and device therapies variably employ randomization and blinding.

Left ventricular (LV) thrombus is a feared complication of LV dysfunction associated with high rates of systemic embolism, morbidity, and mortality. Traditionally, LV thrombus has been associated with acute myocardial infarction (MI). However, with improvements in percutaneous coronary intervention

BACKGROUND The periosteum is a thin membrane that covers almost all bony surfaces in the human body. This membrane is attached to the underlying bone through type I collagen fibers known as Sharpey's fibers. The periosteum is organized into an inner cellular layer with significant osteoblastic potential and an outer fibrous layer. This osteoblastic potential can be stimulated by both physiologic processes in growth and fracture repair and by pathologic conditions. The characteristics of the periosteal responses are modulated by factors such as the type of initiating stimulus, age, and anatomic site. CASE REPORT Through illustrative cases, we will discuss the biologic bases for periosteal responses and the association of these radiologic presentations with pathophysiologic situations such as in inflammation and malignancy. DISCUSSION/CONCLUSIONS This poster will review the gross and cellular anatomy of the periosteal membrane and a range of periosteal responses. An understanding of bone and periosteal biology serves as a foundation for a radiologist to recognize patterns of periosteal responses and to decipher the causative stimuli.

Background: Racial inequities for patients with heart failure (HF) have been widely documented. HF patients who receive cardiology care during a hospital admission have better outcomes. It is unknown whether there are differences in admission to a cardiology or general medicine service by race. This study examined the relationship between race and admission service, and its effect on 30-day readmission and mortality Methods: We performed a retrospective cohort study from September 2008 to November 2017 at a single large urban academic referral center of all patients self-referred to the emergency department and admitted to either the cardiology or general medicine service with a principal diagnosis of HF, who self-identified as white, black, or Latinx. We used multivariable generalized estimating equation models to assess the relationship between race and admission to the cardiology service. We used Cox regression to assess the association between race, admission service, and 30-day readmission and mortality. Results: Among 1967 unique patients (66.7% white, 23.6% black, and 9.7% Latinx), black and Latinx patients had lower rates of admission to the cardiology service than white patients (adjusted rate ratio, 0.91; 95% CI, 0.84–0.98, for black; adjusted rate ratio, 0.83; 95% CI, 0.72–0.97 for Latinx). Female sex and age >75 years were also independently associated with lower rates of admission to the cardiology service. Admission to the cardiology service was independently associated with decreased readmission within 30 days, independent of race. Conclusions: Black and Latinx patients were less likely to be admitted to cardiology for HF care. This inequity may, in part, drive racial inequities in HF outcomes.

Background: While alarms on hospital telemetry units are vital to patient safety, alarm fatigue is a well-established and potentially dangerous consequence. Our goal was to implement an alarm management pilot to systematically determine how to safely reduce alarm burden. Methods: The Brigham and Women’s Hospital Monitoring Steering Committee (BWH MSC) studied the effect of alarm fatigue from March to November 2014 in a multiweek, phased pilot (Figure 1). The intervention groups were two medical/surgical stepdown units (group 1) and three cardiac stepdown units (group 2). The control group was a combination of two medical/surgical units and one cardiac stepdown unit. Various interventions were performed in a stepwise and cumulative manner. Electrodes were switched on a daily basis. The high heart rate (HR) alarm threshold was increased from 120 to 130 beats per minute (bpm) and the low HR threshold was decreased from 50 to 45 bpm. Duplicate alarms (e.g. “tachy” alarm same as high HR parameter alarm) and non-actionable alarms (e.g. “couplets”) were switched to messages (non-audible). Alarm data was pulled and analyzed on a weekly basis. Results: At baseline, there was wide fluctuation in alarms monitored/week across all three groups; however, the peak alarm unit averaged roughly 400 audible, unique alarms/bed/day. Heart rate alarms decreased by 54% after phase 2 in group 1 and 48% after phase 2 in group 2 (Figure 1). Audible alarms were reduced in phase 3 and 4, most notably by making non-actionable alarms inaudible (34% decrease in phase 3 in group 1, 64% decrease in phase 4 in group 2). Electrode alarms appeared to be mildly reduced in phase 1 and 2 (4-24%), however, these findings were not consistent in phase 3 and 4. Conclusions: Alarm type and burden varied widely across time and hospital units, making it difficult to generalize interventions. However, based on the pilot results, the BWH MSC implemented the following changes across all telemetry units: 1) high HR limit and low HR limits were made more permissive as above, and 2) duplicate and non-actionable alarms were made non-audible. The latter intervention was thought to provide the greatest impact based on our experience. While this pilot represented a systematic approach to reduce alarm burden, ongoing efforts to safely improve alarm burden are warranted.

Often, new social movements engaged with science and society are characterised as contesting objectivity; the neutrality of modern science seeking to legitimise ‘lay perspectives’. It has been an article of faith among scholars to view third world movements as anti-science, anti-modernity and post-developmentalist. This commentary describes ideological framework, modes of action and organisation of the All India People’s Science Network (AIPSN), one of the People’s science movement (PSMs) active for more than the past four decades. They dispute the dominant development trajectory and science and technology-related policies for reinforcing the existing inequities. Nevertheless, they see ‘science’ as a powerful ally for realising their radical emancipatory vision of ‘science for social revolution’. Mobilising ‘science activists’ as unique alternate communicators, they strive for lay-expert collaboration. The canonical framing of third world social movements as postcolonial and anti-modern does not capture this unique case from India. Further studies are required to tease out such strands of social movements elsewhere.

Breaking a Sweat This interactive case features a patient with 3-week history of worsening chills and intermittent fevers. He also reported the recent onset of drenching night sweats, generalized m...

BACKGROUND: While open access publishing among cardiovascular journals has increased in scope over the last decade, the relationship between open access and article citation volume remains unclear. METHODS: We evaluated the association between open access publishing and citation number in 2017 among 4 major cardiovascular journals. Articles indexed to PubMed with ≥5 citations were identified among the following journals: Circulation, European Heart Journal, Journal of the American College of Cardiology, and JAMA Cardiology. Multivariable Poisson regression models were adjusted for journal and article type. RESULTS: Of the 916 articles published in 2017, original investigations accounted for most articles (66.7%), followed by reviews (14.5%), guideline/scientific statements (8.4%), research letters (3.7%), viewpoints (3.7%), and editorials (2.9%). Among all articles, 43% (n=391) were open access. Citation number was higher among open access articles compared with those with subscription access (14 [25(th)-75(th) percentile: 9-23] vs. 11 [25(th)-75(th) percentile: 7-17]; P

The early part of the nineteenth century witnessed the widespread circulation of printed pancāṅga (traditional Hindu calendars or almanacs) in the Madras presidency. Computed using the vākya algorithms, these pancāṅga were full of errors, such as local circumstances of eclipses. Chinthamani Ragoonatha Charry, hailed as the first Indian to make modern astronomical discoveries and an employee of the Madras Astronomical Observatory, advocated the reform of the traditional South Indian pancāṅga. Unhappy about the errors in the traditional pancāṅga, during the 1870s he took it upon himself to publish ‘scientific’ pancāṅga in Tamil and Telugu, two principle languages of the presidency, drawing upon the computations of modern astronomy. These almanacs confirmed to the ritual demands of the traditional pancāṅga even while drawing upon elements of the almanacs published by the British settlers in the Madras Presidency. Charry’s pancāṅga not only provided the computation of traditional elements, such as tithi, nākṣatra, yoga and karaṇa, but also elaborated on stellar phenomena, particularly those which are visible to the naked eye, and gave accurate predictions for solar and lunar eclipses, occultations, and so on. Convinced by the arguments advocated by Charry and the accuracy of his predictions, two major religious sects—the Smārta sect of Kanchi Kamokoti Mutt and the Aiyangar subsect owing allegiance to Jeears of Ahobila Mutt—supported his ‘scientific’ pancāṅga.

Cangrelor has a potentially favorable pharmacodynamic profile in cardiogenic shock (CS). We aimed to evaluate the clinical course of CS patients undergoing percutaneous coronary intervention (PCI) treated with cangrelor.We retrospectively identified 136 CS patients treated with cangrelor. Patients were 1:1 matched to CS patients from the IABP-SHOCK II trial not receiving cangrelor by age, sex, cardiac arrest, type of myocardial infarction, culprit lesion, glycoprotein IIb/IIIa inhibitor, and oral P2YCangrelor treatment was associated with similar bleeding risk and significantly better TIMI flow improvement compared with oral P2Y

Although a substantial proportion of patients with heart failure (HF) have anemia, there is a paucity of data evaluating the impact of anemia on clinical outcome in CRT patients. Our goal was to examine the ability of baseline hemoglobin (Hb) level and change in Hb level over time to predict clinical 2-year outcome and echocardiographic response to CRT. Three hundred consecutive CRT patients (median 72 years [interquartile range (IQR) 16 years], 19 % female) with baseline and follow-up hematological profiles available were examined. Baseline anemia was defined as Hb

This analysis sought to systematically characterize trial-level patterns in atrial fibrillation/atrial flutter (AF/AFL) by using the ClinicalTrials.gov database.Despite an abundance of clinical trials in this field, there is a lack of high-level evidence guiding management of AF/AFL.We queried all closed, phase II to IV interventional trials registered in the ClinicalTrials.gov database through October 2016 that enrolled patients known to have AF/AFL. Published trials were evaluated for methodological quality, using the 3-item Jadad scale (range: 0 to 5, where 5 = highest quality).The initial search yielded 465 uniquely registered studies, of which 348 directly studied AF/AFL. Of those studies, 173 (50%) were published, enrolling a median of 190 patients from a median of 15 sites. The volume of published trials increased over time (7% prior to 2008 vs. 41% from 2014 to 2016; p 0.001 for trend). Of the completed trials, 29% remain unpublished. Industry sources accounted for most funding (54%). Recurrence of AF/AFL was the most common endpoint (45%), whereas rates of primary clinical endpoints were low (13%). The mean Jadad score of published trials of pharmacological approaches (n = 112) was 4.0 ± 1.4. Of the 61 AF/AFL trials involving ablation or device therapies, 69% were randomized, 28% were single-arm studies, and patient, proceduralist, and event-ascertainment blinding was used in 16%, 4%, and 44%, respectively.Contemporary trials of AF/AFL are often multicenter and modest in size. The primary study endpoint is commonly recurrence of arrhythmia, even in high-quality and late-phase trials. Although methodological quality is high in trials of pharmacologic approaches, trials of AF/AFL ablation and device therapies variably employ randomization and blinding.

Introduction The circadian clock regulates murine immune responses by time of day, partly through the clock protein REVERBα, resulting in altered mortality after infection. The mechanisms regulating time of day differences are poorly understood in humans, where performing circadian studies presents a number of challenges. Lung transplantation, which is performed at any time of day to minimise organ ischaemic time, is an ideal model to study circadian effects on human immune responses. Methods Primary graft dysfunction (PGD) incidence after lung transplantation was examined for an eight year retrospective (2004–2012) cohort (n=563) in one centre. Patients were excluded, a priori, if they had significant intra-operative complications, had a previous lung transplant, or if the donor lung had undergone ex-vivo perfusion. Circadian factors were also studied using PER2::Luc and REVERBα-/- mice and by pharmacological targeting of the circadian clock in primary alveolar macrophages from lung transplant recipients. Results The incidence of PGD grades 2/3 at 24 hours was temporarily elevated when organs were reperfused between 4 and 8 am (p Conclusion This study suggests that the circadian clock could temporarily affect outcomes after lung transplantation due to recipient-donor circadian desynchrony. Ligands targeting the clock protein REVERBα repress key PGD biomarkers showing that this is a tractable therapeutic pathway.

From the ISHLT Transplant Registry, Dallas, Texas; University of Utah School of Medicine, Salt Lake City, Utah; Brigham and Women’s Hospital Heart and Vascular Center, Harvard University, Boston, Massachusetts; Hospital Universitario A Coruna, La Coruna, Spain; Hospital 12 de Octubre, Madrid, Spain; Agence de la biomedecine, Saint-Denis, France; Niguarda-Ca’ Granda Hospital, Milan, Italy; St. Vincent’s Hospital, Sydney, New South Wales, Australia; Freeman Hospital, Newcastle upon Tyne, United Kingdom; Centro Nazionale Trapianti, Roma, Italy; Duke University, Durham, North Carolina; The Johns Hopkins Hospital, Baltimore, Maryland; National Health Service Blood and Transplant, Bristol, United Kingdom; and the Wythenshawe Hospital, Manchester, United Kingdom.

This interactive case features a 52-year-old man of West African origin who presents with nausea, vomiting, and profound lethargy. Test your diagnostic and therapeutic skills at NEJM.org.

Left ventricular (LV) thrombus is a feared complication of LV dysfunction associated with high rates of systemic embolism. However, contemporary data are lacking. We identified patients diagnosed with LV thrombus on echocardiography (±contrast) at Brigham and Women's Hospital between January 2008

We approach a special system for smart parking reservation and security maintenance in a commercial car parking area in an urban environment. This system mainly designed to avoid unnecessary time conception to find an empty lot in a car parking area. By the same case we can also save more than 80% of fuel wastage in a car parking area to finds the empty parking slot. The reservation process is happening only by user. Hence the user finds the empty parking lot and makes the action of reservation through an internet access by an embedded process control unit (EPCU) with driver’s own knowledge. Here we give the major response to user’s reservation action and hence the driver can reserve his own likely parking slot based on the cost function. Instead of efficient car parking we need a special security options to make our vehicle very safe. By this case we have provided a best security guidance of barrier gate control security system (BGCSS) with the help of embedded process control unit (EPCU). There are number of steps taken to make a reservation with different lighting scheme mechanism (DLSM). We have proposed a system with multi-processing queuing mechanism (MPQM) to avoid multi-user approach problem (MUAP) during reservation process in our smart parking reservation system.

During the International Year of Chemistry 2011, Vigyan Prasar and All India Radio entered into an agreement to produce radio serials jointly on 117 radio stations in 19 major Indian languages. The programme presented chemistry as a ubiquitous aspect of our surroundings with the goal of evoking public appreciation and building greater understanding of chemistry among the general public. The programme highlighted activities by Indian scientists, with a special focus on young researchers and new technologies developed in Indian research laboratories. This case study describes the narrative structure, targeted audience, and strategies adopted in the project. Our results should be useful for similar educational initiatives targeting comparable radio audiences.

Background: Acute respiratory distress syndrome (ARDS) is seen in critically ill patients. Its etiological spectrum in India is expected to be different from that seen in western countries due to the high prevalence of tropical infections. Aim: To study the epidemiological profile of ARDS patients. Setting: A tertiary care hospital in Karnataka, India. Materials and Methods: Retrospective analysis of 150 out of the 169 ARDS patients diagnosed during 2010–2012. Data collected included the clinical features and severity scoring parameters. Results: The mean age of the study population was 42.92 ± 13.91 years. The causes of ARDS included pneumonia ( n = 35, 23.3%), scrub typhus ( n = 33, 22%), leptospirosis ( n = 11, 7.3%), malaria ( n = 6, 4%), influenza (H1N1) ( n = 10, 6.7%), pulmonary tuberculosis ( n = 2, 1.3%), dengue ( n = 1, 0.7%), abdominal sepsis ( n = 16, 10.7%), skin infection ( n = 3, 2%), unknown cause of sepsis ( n = 18, 12%), and nonseptic causes ( n = 15, 10%). A total of 77 (51.3%) patients survived, 66 (44%) expired, and 7 (4.7%) were discharged against medical advice (AMA). Preexisting comorbidities (46) were present in 13 survivors, 19 nonsurvivors, and four discharged AMA. History of surgery prior to the onset of ARDS was present in one survivor, 13 nonsurvivors, and one discharge AMA. Mean Acute Physiology and Chronic Health Evaluation (APACHE) II, APACHE III, and Sequential Organ Failure Assessment scores in survivors were 9.06 ± 4.3, 49.22 ± 14, and 6.43 ± 2.5 and in nonsurvivors 21.11 ± 7, 86.45 ± 23.5, and 10.6 ± 10, respectively. Conclusion: The most common cause of ARDS in our study was pneumonia, but a large percentage of cases were due to the tropical infections. Preexisting comorbidity, surgery prior to the onset of ARDS, higher severity scores, and organ failure scores were more frequently observed among nonsurvivors than survivors.

Media, in particular television, significantly influence the public sphere and construct what constitutes our common sense in the modern world. If we desire science and technology to be part of culture, then science needs to be present on television as a routine. On this premise and drawing from the international experiences and empirical studies on science on television, particularly in Europe, this chapter argues that in addition to regulation various measures are required in contemporary scenario to enhance airtime for science in India.

In recent years, due to the geological and anthropogenic activities, metal pollution in soil has been increased drastically. Utilization of microorganisms to remediate the metal-contaminated soil is known as bioremediation. Bioremediation is an important area of research that offers economically effective clean-up technique than the conventional methods. Microorganisms use different mechanisms such as biosorption, bioaccumulation, chelating agents, bioleaching, biomineralization and enzyme-catalysed transformation to convert toxic form of metals to less toxic form. In addition, plants also offer various methods like absorption and accumulation of metals in plant cells and formation of metal-bound compounds. Integrated use of microorganism and plant in bioremediation may ensure an effective clean-up of heavy metals in polluted soils. This chapter summarizes the microbial- and plant-microbe-mediated methods for the clean-up of heavy metal-contaminated soil.

Aneuploidy is a hallmark of most human tumors, but the molecular physiology of aneuploid cells is not well characterized. In this study, we screened cell surface biomarkers of approximately 300 proteins by multiparameter flow cytometry using multiple aneuploid model systems such as cell lines, patient samples, and mouse models. Several new biomarkers were identified with altered expression in aneuploid cells, including overexpression of the cellular prion protein CD230/PrP

A novel radical induced fragmentation in a benzoxocane ring system has been employed for a synthesis of elvirol 8 and an advanced intermediate in the synthesis of 7,8-dihydroxycalamenene 20. The coumarins 9, 22 were taken through a sequence of reactions to the benzoxocanols 16, 30, which when subjected to Barton’s deoxygenation conditions involving conversion to the corresponding thionocarbonates 17, 31 followed by exposure to tri-n-butyltin hydride, underwent a radical induced fragmentation to furnish elvirol 8 and the curcuphenol derivative 32, which was converted to the dimethoxy compound 33. This had served as an advanced intermediate in a previous synthesis of dihydroxycalamenene.