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1.  Randomized controlled trial of atorvastatin in clinically isolated syndrome 
Neurology  2012;78(15):1171-1178.
Objective:
To test efficacy and safety of atorvastatin in subjects with clinically isolated syndrome (CIS).
Methods:
Subjects with CIS were enrolled in a phase II, double-blind, placebo-controlled, 14-center randomized trial testing 80 mg atorvastatin on clinical and brain MRI activity. Brain MRIs were performed quarterly. The primary endpoint (PEP) was development of ≥3 new T2 lesions, or one clinical relapse within 12 months. Subjects meeting the PEP were offered additional weekly interferon β-1a (IFNβ-1a).
Results:
Due to slow recruitment, enrollment was discontinued after 81 of 152 planned subjects with CIS were randomized and initiated study drug. Median (interquartile range) numbers of T2 and gadolinium-enhancing (Gd) lesions were 15.0 (22.0) and 0.0 (0.0) at baseline. A total of 53.1% of atorvastatin recipients (n = 26/49) met PEP compared to 56.3% of placebo recipients (n = 18/32) (p = 0.82). Eleven atorvastatin subjects (22.4%) and 7 placebo subjects (21.9%) met the PEP by clinical criteria. Proportion of subjects who did not develop new T2 lesions up to month 12 or to starting IFNβ-1a was 55.3% in the atorvastatin and 27.6% in the placebo group (p = 0.03). Likelihood of remaining free of new T2 lesions was significantly greater in the atorvastatin group compared with placebo (odds ratio [OR] = 4.34, p = 0.01). Likelihood of remaining free of Gd lesions tended to be higher in the atorvastatin group (OR = 2.72, p = 0.11). Overall, atorvastatin was well tolerated. No clear antagonistic effect of atorvastatin plus IFNβ-1a was observed on MRI measures.
Conclusion:
Atorvastatin treatment significantly decreased development of new brain MRI T2 lesion activity, although it did not achieve the composite clinical and imaging PEP.
Classification of Evidence:
This study provided Class II evidence that atorvastatin did not reduce the proportion of patients with CIS meeting imaging and clinical criteria for starting immunomodulating therapy after 12 months, compared to placebo. In an analysis of a secondary endpoint (Class III), atorvastatin was associated with a reduced risk for developing new T2 lesions.
doi:10.1212/WNL.0b013e31824f7fdd
PMCID: PMC3320055  PMID: 22459680
2.  Diminished ovarian reserve, premature ovarian failure, poor ovarian responder—a plea for universal definitions 
Purpose
Diminished ovarian reserve (DOR) is characterized by poor fertility outcomes, and it represents a major challenge in reproductive medicine. Although consensus exists on the concept of DOR, its definition remains blurry. DOR has to be distinguished from premature ovarian failure (POF) and poor ovarian responders (POR), who are clearly defined.
Methods
We performed a PubMed search with the terms “diminished ovarian reserve” and “in vitro fertilization (IVF)” to assess the homogeneity of the definition of DOR.
Results
Out of 121 articles, 14 gave a definition for DOR. Only one definition was used by two different teams (basal follicle-stimulating hormone (FSH) value >10 IU/l) and eight teams used 11 different definitions. Among those, four definitions did not include antral follicular count (AFC) and seven studies did. Two definitions included the results from a previous cycle.
Conclusions
The heterogeneity in the definition of DOR used in these studies contributes to confusing results. Hence, there is a need for a clear definition of DOR. It appears that AFC and anti-Müllerian hormone (AMH) serum levels are the most relevant criteria. One option could be the use of the following definition: (i) woman with any of the risk factors for POR and/or (ii) an abnormal ovarian reserve test (i.e., antral follicular count (AFC) <5–7 follicles or AMH <0.5–1.1 ng/ml). This hypothesis requires validation.
doi:10.1007/s10815-015-0595-y
PMCID: PMC4681731  PMID: 26463876
Diminished ovarian reserve; IVF; AMH; AFC
3.  Learning curve for endoscopic ultrasound-guided fine-needle aspiration (EUS-FNA) of pancreatic lesions in a novel ex-vivo simulation model 
Endoscopy International Open  2016;4(12):E1286-E1291.
Background: Endoscopic ultrasound-guided fine-needle aspiration (EUS-FNA) is essential in the management of digestive cancers. However, teaching and learning this technique remain challenging due to the lack of cost-effective models.
Material and methods: This was a prospective experimental study using a complete porcine upper gastrointestinal ex-vivo organ package, placed in an Erlangen Active Simulator for Interventional Endoscopy (EASIE-R), and prepared with one cyst and two solid masses (2 cm). Five fellows inexperienced in EUS-FNA were enrolled, performing 10 procedures on each lesion, alternatively. The total time, number of attempts for success, of needle view losses, and of scope handling were recorded, associated with an independent skills rating by procedure. We compared the first 15 procedures with the last 15 for each fellow.
Results: The fellows successfully performed all procedures in 2 to 40 minutes, requiring 1 to 6 attempts. All (5/5) improved their total time taken (P < 0.001), number of times when the EUS view of the needle was lost (P < 0.05), scope handling (P < 0.005), and skills rating (P < 0.001), whereas 4/5 (80 %) improved their number of attempts. The overall evaluation showed a significant decrease (P < 0.001) in the total time taken (11.2 ± 7.8 vs 4.3 ± 2.2 minutes), number of attempts (2.6 ± 1.2 vs 1.2 ± 0.7), number of times when the EUS view of the needle was lost (2.3 ± 2 vs 0.5 ± 0.7), and need for scope handling (1.1 ± 1.7 vs 0.1 ± 0.2). We also observed an improvement in skills rating (5 ± 1.9 vs. 7.7 ± 1.1).
Conclusion: This newly designed ex-vivo model seems to be an effective way to improve the initial learning of EUS-FNA, by performing 30 procedures.
doi:10.1055/s-0042-118176
PMCID: PMC5161137  PMID: 27995190
4.  International study of the place of death of people with cancer: a population-level comparison of 14 countries across 4 continents using death certificate data 
British Journal of Cancer  2015;113(9):1397-1404.
Background:
Where people die can influence a number of indicators of the quality of dying. We aimed to describe the place of death of people with cancer and its associations with clinical, socio-demographic and healthcare supply characteristics in 14 countries.
Methods:
Cross-sectional study using death certificate data for all deaths from cancer (ICD-10 codes C00-C97) in 2008 in Belgium, Canada, Czech Republic, England, France, Hungary, Italy, Mexico, the Netherlands, New Zealand, South Korea, Spain (2010), USA (2007) and Wales (N=1 355 910). Multivariable logistic regression analyses evaluated factors associated with home death within countries and differences across countries.
Results:
Between 12% (South Korea) and 57% (Mexico) of cancer deaths occurred at home; between 26% (Netherlands, New Zealand) and 87% (South Korea) occurred in hospital. The large between-country differences in home or hospital deaths were partly explained by differences in availability of hospital- and long-term care beds and general practitioners. Haematologic rather than solid cancer (odds ratios (ORs) 1.29–3.17) and being married rather than divorced (ORs 1.17–2.54) were most consistently associated with home death across countries.
Conclusions:
A large country variation in the place of death can partly be explained by countries' healthcare resources. Country-specific choices regarding the organisation of end-of-life cancer care likely explain an additional part. These findings indicate the further challenge to evaluate how different specific policies can influence place of death patterns.
doi:10.1038/bjc.2015.312
PMCID: PMC4815784  PMID: 26325102
cancer; place of death; death certificates; end-of-life care; cross-national comparison
6.  Cell-free DNA and telomere length among women undergoing in vitro fertilization treatment 
Purpose
The current research is aimed at finding potential non-invasive bio-markers that will help us learn more about the mechanisms at play in failed assisted reproduction treatment. This exploratory pilot study examined the relationship between cell-free DNA (CFD) in plasma and telomere length in lymphocytes among women undergoing in vitro fertilization (IVF) and compared telomere length and CFD levels to a healthy control group.
Methods
Blood of 20 women undergoing IVF was collected at three time points during the IVF cycle. We assessed the relationship between CFD and telomere length as well as controlling for morning cortisol levels. We also collected blood of 10 healthy controls at two time points (luteal and follicular phases of the menstrual cycle) and compared mean telomere length, CFD, and cortisol levels between the IVF patients and healthy controls.
Results
The results revealed an inverse relationship between CFD levels and telomere lengths at several time points that remained significant even after controlling for cortisol levels. Women undergoing IVF had statistically significant higher levels of CFD and shorter telomeres compared to healthy controls.
Conclusions
The relationship between telomere length and CFD should be further explored in larger studies in order to uncover potential mechanisms that cause both shortened telomere length and elevated CFD in women undergoing IVF.
doi:10.1007/s10815-015-0581-4
PMCID: PMC4651952  PMID: 26438644
In vitro fertilization; Cell-free DNA; Telomere length; Cortisol
7.  Decompressive laparotomy for abdominal compartment syndrome 
The British Journal of Surgery  2016;103(6):709-715.
Background
The effect of decompressive laparotomy on outcomes in patients with abdominal compartment syndrome has been poorly investigated. The aim of this prospective cohort study was to describe the effect of decompressive laparotomy for abdominal compartment syndrome on organ function and outcomes.
Methods
This was a prospective cohort study in adult patients who underwent decompressive laparotomy for abdominal compartment syndrome. The primary endpoints were 28‐day and 1‐year all‐cause mortality. Changes in intra‐abdominal pressure (IAP) and organ function, and laparotomy‐related morbidity were secondary endpoints.
Results
Thirty‐three patients were included in the study (20 men). Twenty‐seven patients were surgical admissions treated for abdominal conditions. The median (i.q.r.) Acute Physiology And Chronic Health Evaluation (APACHE) II score was 26 (20–32). Median IAP was 23 (21–27) mmHg before decompressive laparotomy, decreasing to 12 (9–15), 13 (8–17), 12 (9–15) and 12 (9–14) mmHg after 2, 6, 24 and 72 h. Decompressive laparotomy significantly improved oxygenation and urinary output. Survivors showed improvement in organ function scores, but non‐survivors did not. Fourteen complications related to the procedure developed in eight of the 33 patients. The abdomen could be closed primarily in 18 patients. The overall 28‐day mortality rate was 36 per cent (12 of 33), which increased to 55 per cent (18 patients) at 1 year. Non‐survivors were no different from survivors, except that they tended to be older and on mechanical ventilation.
Conclusion
Decompressive laparotomy reduced IAP and had an immediate effect on organ function. It should be considered in patients with abdominal compartment syndrome.
Improves organ function
doi:10.1002/bjs.10097
PMCID: PMC5067589  PMID: 26891380
8.  A phase II/III randomized study to compare the efficacy and safety of rigosertib plus gemcitabine versus gemcitabine alone in patients with previously untreated metastatic pancreatic cancer† 
Annals of Oncology  2015;26(9):1923-1929.
Gemcitabine offers modest benefit in treatment of metastatic pancreatic cancer. Rigosertib, a small-molecule inhibitor of multiple effector pathways important in tumorgenesis and metastasis, has shown synergistic effects in combination with gemcitabine in preclinical pancreatic cancer models. This study investigated the efficacy and safety of rigosertib plus gemcitabine versus gemcitabine alone.
Background
Rigosertib (ON 01910.Na), a first-in-class Ras mimetic and small-molecule inhibitor of multiple signaling pathways including polo-like kinase 1 (PLK1) and phosphoinositide 3-kinase (PI3K), has shown efficacy in preclinical pancreatic cancer models. In this study, rigosertib was assessed in combination with gemcitabine in patients with treatment-naïve metastatic pancreatic adenocarcinoma.
Materials and methods
Patients with metastatic pancreatic adenocarcinoma were randomized in a 2:1 fashion to gemcitabine 1000 mg/m2 weekly for 3 weeks of a 4-week cycle plus rigosertib 1800 mg/m2 via 2-h continuous IV infusions given twice weekly for 3 weeks of a 4-week cycle (RIG + GEM) versus gemcitabine 1000 mg/m2 weekly for 3 weeks in a 4-week cycle (GEM).
Results
A total of 160 patients were enrolled globally and randomly assigned to RIG + GEM (106 patients) or GEM (54). The most common grade 3 or higher adverse events were neutropenia (8% in the RIG + GEM group versus 6% in the GEM group), hyponatremia (17% versus 4%), and anemia (8% versus 4%). The median overall survival was 6.1 months for RIG + GEM versus 6.4 months for GEM [hazard ratio (HR), 1.24; 95% confidence interval (CI) 0.85–1.81]. The median progression-free survival was 3.4 months for both groups (HR = 0.96; 95% CI 0.68–1.36). The partial response rate was 19% versus 13% for RIG + GEM versus GEM, respectively. Of 64 tumor samples sent for molecular analysis, 47 were adequate for multiplex genetic testing and 41 were positive for mutations. The majority of cases had KRAS gene mutations (40 cases). Other mutations detected included TP53 (13 cases) and PIK3CA (1 case). No correlation between mutational status and efficacy was detected.
Conclusions
The combination of RIG + GEM failed to demonstrate an improvement in survival or response compared with GEM in patients with metastatic pancreatic adenocarcinoma. Rigosertib showed a similar safety profile to that seen in previous trials using the IV formulation.
doi:10.1093/annonc/mdv264
PMCID: PMC4551155  PMID: 26091808
pancreatic cancer; phase II/III; PI3K inhibitor; PLK1 inhibitor; Ras mimetic; rigosertib
9.  The potential risks and impact of the start of the 2015–2016 influenza season in the WHO European Region: a rapid risk assessment 
Tjon‐Kon‐Fat, Raïssa | Meerhoff, Tamara | Nikisins, Sergejs | Pires, João | Pereyaslov, Dmitriy | Gross, Diane | Brown, Caroline | Drishti, A. | Hasibra, I. | Kota, M. | Simaku, A. | Sarkisian, S. | Torosyan, L. | El Belazi, G. | Hain, C. | Lachner, P. | Muchl, R. | Popow‐Kraupp, T. | Redlberger‐Fritz, M. | Strauss, R. | Abdullayeva, N. | Salimov, O. | Gribkova, N. | Shimanovich, V. | Bossuyt, N. | Hombrouck, A. | Moreels, S. | Thomas, I. | an Casteren, . | Bastinac, D. | Dedejic Ljubovic, A. | Kojic, D. | Kovacevic Suljkanovic, M. | Kuzmanovic, M. | Vukmir Rodic, N. | Georgieva, T. | Kojouharova, M. | Korsun, N. | Drazenovic, V. | Erceg, M. | Kurecic‐Filipovic, S. | Simunovic, A. | Visekruna, V.V. | Bagatzouni, D. | Elia, A. | Koliou, M. | Havlickova, M. | Jirincova, H. | Kyncl, J. | Bragstad, K. | Kolsen Fischer, T. | Krause, K.L. | Mazick, A. | Trebbien, R. | Dontsenko, I. | Dotsenko, L. | Pokras, L. | Sadikova, O. | Ikonen, N. | Lyytikainen, O. | Murtopuro, S. | Ruutu, P. | Behillil, S. | Belchior, E. | Blanchon, T. | Bonmarin, I. | Bruno, L. | Cohen, J.M. | Enouf, V. | Levy, B.D. | Mosnier, A. | Turbelin, C. | Valette, M. | an der Werf, . | Chakhunashvili, G. | Machablishvili, A. | Zakhashvili, K. | Andreas, G. | Buda, S. | Eckmanns, T. | Krause, G. | Poggensee, G. | Schweiger, B. | Kossivakis, A. | Malisiovas, N. | Mentis, A. | Spala, G. | Csohan, A. | Jankovics, I. | Kaszas, K. | Molnar, Z. | Rozsa, M. | Gudnason, T. | Löve, A. | Sigmundsdottir, G. | Coughlan, S. | Domegan, L. | Duffy, M. | Igoe, D. | O'Donnell, J. | O'Flanagan, D. | Waters, A. | Kaufman, Z. | Mandelboim, M. | Bella, A. | Donatelli, I. | Pompa, M.G. | Rizzo, C. | Amandosova, D. | Kuatbaeva, A. | Nusupbaeva, G. | Smagulova, M. | Smagul, M. | Sultanova, M. | Otorbaeva, D. | Saparova, G. | Butirina, R. | Nikiforova, R. | Storozenko, J. | Zamjatina, N. | Griskevicius, A. | Lipnickiene, V. | Muralyte, S. | Mossong, J. | Opp, M. | Barbara, C. | Graziella, Z. | Maistre, M.J. | Melillo, T. | Rakocevic, B. | Vratnica, Z. | Hooiveld, I. | de Lange, M. | Dijkstra, F. | Donker, G. | Meijer, A. | Rimmelzwaan, G. | Teirlinck, A. | van der Hoek, W. | Dudman, S. | Hauge, S.H. | Hungnes, O. | Kilander, A. | Tonnessen, R. | Bednarska, K. | Brydak, L. | Wozniak‐Kosek, A. | Zielinski, A. | Guiomar, R. | Nunes, B. | Eder, V. | Spinu, C. | Alexandrescu, V. | Lupulescu, E. | Popovici, F. | Burtseva, E. | Komissarov, A. | Smorodintseva, E. | Sominina, A. | Dimitrijevic, D. | Filipovic, S. | Staronova, E. | Berginc, N. | Prosenc, K. | Socan, M. | Ucakar, V. | Grgic Vitek, M. | Casas, I. | de Lejarazu, R. Ortiz | Larrauri, A. | Pozo, F. | Vega, T. | Ali, M. | Brytting, M. | Dahl, H. | Englund, H. | Tegnell, A. | Wallensten, A. | Wiman, A. | Born, R. | Cordey, S. | Kamolov, M. | Bosevska, G. | Karadzovski, Z. | Kuzmanovska, G. | Mikik, V. | Korukluoglu, G. | Topal, S. | Ashyrova, A. | Ovliyakulova, G. | Demchyshyna, I. | Dykhanovska, T. | Mironenko, A. | Blatchford, O. | Carman, W. | Coyle, P. | Gunson, R. | Kearns, C. | MacLean, A. | Mcmenamin, J. | Moore, C. | Nugent, C. | Pebody, R. | Phin, N. | Reynolds, A. | Smyth, B. | Watson, J. | Zambon, M. | Dzemileva, S. | Rakhimov, R.
Background
Countries in the World Health Organization (WHO) European Region are reporting more severe influenza activity in the 2015–2016 season compared to previous seasons.
Objectives
To conduct a rapid risk assessment to provide interim information on the severity of the current influenza season.
Methods
Using the WHO manual for rapid risk assessment of acute public health events and surveillance data available from Flu News Europe, an assessment of the current influenza season from 28 September 2015 (week 40/2015) up to 31 January 2016 (week 04/2016) was made compared with the four previous seasons.
Results
The current influenza season started around week 51/2015 with higher influenza activity reported in Eastern Europe compared to Western Europe. There is a strong predominance of influenza A(H1N1)pdm09 compared to previous seasons, but the virus is antigenically similar to the strain included in the seasonal influenza vaccine. Compared to the 2014/2015 season, there was a rapid increase in the number of severe cases in Eastern European countries with the majority of such cases occurring among adults aged <65 years.
Conclusions
The current influenza season is characterized by an early start in Eastern European countries, with indications of a more severe season. Currently circulating influenza A(H1N1)pdm09 viruses are antigenically similar to those included in the seasonal influenza vaccine, and the vaccine is expected to be effective. Authorities should provide information to the public and health providers about the current influenza season, recommendations for the treatment of severe disease and effective public health measures to prevent influenza transmission.
doi:10.1111/irv.12381
PMCID: PMC4910174  PMID: 26918771
2015–2016 Influenza season; influenza A(H1N1)pdm09 virus; seasonal influenza; WHO European Region
10.  Multitasking vs. multiplexing: Toward a normative account of limitations in the simultaneous execution of control-demanding behaviors 
Why is it that behaviors that rely on control, so striking in their diversity and flexibility, are also subject to such striking limitations? Typically, people cannot engage in more than a few — and usually only a single — control-demanding task at a time. This limitation was a defining element in the earliest conceptualizations of controlled processing, it remains one of the most widely accepted axioms of cognitive psychology, and is even the basis for some laws (e.g., against the use of mobile devices while driving). Remarkably, however, the source of this limitation is still not understood. Here, we examine one potential source of this limitation, in terms of a tradeoff between the flexibility and efficiency of representation (“multiplexing”) and the simultaneous engagement of different processing pathways (“multitasking”). We show that even a modest amount of multiplexing rapidly introduces cross-talk among processing pathways, thereby constraining the number that can be productively engaged at once. We propose that, given the large number of advantages of efficient coding, the human brain has favored this over the capacity for multitasking of control-demanding processes.
doi:10.3758/s13415-013-0236-9
PMCID: PMC4845905  PMID: 24481850
11.  The effect of malaria control on Plasmodium falciparum in Africa between 2000 and 2015 
Nature  2015;526(7572):207-211.
Since the year 2000, a concerted campaign against malaria has led to unprecedented levels of intervention coverage across sub-Saharan Africa. Understanding the effect of this control effort is vital to inform future control planning. However, the effect of malaria interventions across the varied epidemiological settings of Africa remains poorly understood owing to the absence of reliable surveillance data and the simplistic approaches underlying current disease estimates. Here we link a large database of malaria field surveys with detailed reconstructions of changing intervention coverage to directly evaluate trends from 2000 to 2015 and quantify the attributable effect of malaria disease control efforts. We found that Plasmodium falciparum infection prevalence in endemic Africa halved and the incidence of clinical disease fell by 40% between 2000 and 2015. We estimate that interventions have averted 663 (542–753 credible interval) million clinical cases since 2000. Insecticide-treated nets, the most widespread intervention, were by far the largest contributor (68% of cases averted). Although still below target levels, current malaria interventions have substantially reduced malaria disease incidence across the continent. Increasing access to these interventions, and maintaining their effectiveness in the face of insecticide and drug resistance, should form a cornerstone of post-2015 control strategies.
doi:10.1038/nature15535
PMCID: PMC4820050  PMID: 26375008
12.  Effect of induced peritoneal endometriosis on oocyte and embryo quality in a mouse model 
Purpose
To assess the impact of peritoneal endometriosis on oocyte and embryo quality in a mouse model.
Methods
Peritoneal endometriosis was surgically induced in 33 B6CBA/F1 female mice (endometriosis group, N = 17) and sham-operated were used as control (sham group, N = 16). Mice were superovulated 4 weeks after surgery and mated or not, to collect E0.5-embryos or MII-oocytes. Evaluation of oocyte and zygote quality was done by immunofluorescence under spinning disk confocal microscopy.
Results
Endometriosis-like lesions were observed in all mice of endometriosis group. In both groups, a similar mean number of MII oocytes per mouse was observed in non-mated mice (30.2 vs 32.6), with a lower proportion of normal oocytes in the endometriosis group (61 vs 83 %, p < 0.0001). Abnormalities were incomplete extrusion or division of the first polar body and spindle abnormalities. The mean number of zygotes per mouse was lower in the endometriosis group (21 vs 35.5, p = 0.02) without difference in embryo quality.
Conclusions
Our results support that induced peritoneal endometriosis in a mouse model is associated with a decrease in oocyte quality and embryo number. This experimental model allows further studies to understand mechanisms of endometriosis-associated infertility.
doi:10.1007/s10815-014-0390-1
PMCID: PMC4354196  PMID: 25399065
Endometriosis; Female infertility; Oocyte development; Embryo quality; Meiosis
14.  P18.05TREATMENT OF ACUTE ISCHEMIC STROKE IN CANCER PATIENTS 
Neuro-Oncology  2014;16(Suppl 2):ii111.
BACKGROUND: Intravenous thrombolysis using tissue plasminogen activator (iv-tPA) and endovascular clot retrieval have revolutionized treatment of acute ischemic stroke. Cancer patients are at increased risk of ischemic stroke because of inherent hypercoagulability. However, the benefit of active thrombolysis in this clinical setting is unknown and treatment with iv-tPA is often avoided because of possible hemorrhagic complications. METHODS: Retrospective screening of the institutional medical records for cancer patients presenting with acute ischemic stroke during the year 2011. Description of 4 representative clinical cases. RESULTS: During the one-year period, 33 cancer patients (16 men and 17 women) presented with and were evaluated for acute ischemic stroke at a mean age of 69 (45-92) years. Of these, 17 (52%) had lacunar strokes, 14 (42%) had large artery strokes and 2 (6%) presented with multiple cardioembolic strokes. At the time of presentation, 14/33 (42%) patients had evidence of systemic metastatic disease and 12/33 (36%) had active locally advanced disease. Most common malignancies included breast cancer, prostatic carcinoma, colorectal and urinary bladder tumors. According to the commonly accepted criteria for intravenous thrombolysis, 3/33 (9%) patients were treated with iv- tPA, and 1/33 (3%) underwent endovascular clot retrieval. No hemorrhagic complications were observed in these 4 patients and all had marked improvement of the neurological disability following treatment. CONCLUSION: Selected cancer patients with acute ischemic stroke may benefit from intravenous thrombolysis and endovascular clot retrieval. Application of the currently accepted clinical criteria for iv-tPA reduces the risk of hemorrhagic complications in this group of patients. Awareness to the available early therapeutic options in this clinical setup may improve outcome of cancer patients with acute ischemic stroke.
doi:10.1093/neuonc/nou174.429
PMCID: PMC4185804
15.  Abdominal Aortic Aneurysm Screening: How Many Life Years Lost from Underuse of the Medicare Screening Benefit? 
Journal of General Internal Medicine  2014;29(8):1155-1161.
ABSTRACT
BACKGROUND
Since 2007, Medicare has provided one-time abdominal aortic aneurysm (AAA) screening for men with smoking history, and men and women with a family history of AAA as part of its Welcome to Medicare visit.
OBJECTIVE
We examined utilization of the new AAA screening benefit and estimated how increased utilization could influence population health as measured by life years gained. Additionally, we explored the impact of expanding screening to women with smoking history.
DESIGN
Analysis of Medicare claims and a simulation model to estimate the effects of screening, using published data for parameter estimates.
SETTING
AAA screening in the primary care setting.
PATIENTS
Newly-enrolled Medicare beneficiaries aged 65 years, with smoking history or family history of AAA.
MAIN MEASURES
Life expectancy, 10-year survival rates.
KEY RESULTS
Medicare data revealed low utilization of AAA screening, under 1 % among those eligible. We estimate that screening could increase life expectancy per individual invited to screening for men with smoking history (0.11 years), with family history of AAA (0.17 years), and women with family history (0.08 years), and smoking history (0.09 years). Average gains of 131 life years per 1,000 persons screened for AAA compare favorably with the grade B United States Preventive Services Task Force (USPSTF) recommendation for breast cancer screening, which yields 95–128 life years per 1,000 women screened. These findings were robust over a range of scenarios.
LIMITATIONS
The simulation results reflect assumptions regarding AAA prevalence, treatment, and outcomes in specific populations based on published research and US survey data. Published data on women were limited.
CONCLUSIONS
The Welcome to Medicare and AAA screening benefits have been underutilized. Increasing utilization of AAA screening would yield substantial gains in life expectancy. Expanding screening to women with smoking history also has the potential for substantial health benefits.
Electronic supplementary material
The online version of this article (doi:10.1007/s11606-014-2831-z) contains supplementary material, which is available to authorized users.
doi:10.1007/s11606-014-2831-z
PMCID: PMC4099445  PMID: 24715406
abdominal aortic aneurysm; screening; medicare; health policy; health services research
16.  Phase I study of capecitabine combined with radioembolization using yttrium-90 resin microspheres (SIR-Spheres) in patients with advanced cancer 
British Journal of Cancer  2014;111(2):265-271.
Background:
This was a prospective single-centre, phase I study to document the maximum tolerated dose (MTD), dose-limiting toxicity (DLT), and the recommended phase II dose for future study of capecitabine in combination with radioembolization.
Methods:
Patients with advanced unresectable liver-dominant cancer were enrolled in a 3+3 design with escalating doses of capecitabine (375–1000 mg/m2 b.i.d.) for 14 days every 21 days. Radioembolization with 90Y-resin microspheres was administered using a sequential lobar approach with two cycles of capecitabine.
Results:
Twenty-four patients (17 colorectal) were enrolled. The MTD was not reached. Haematologic events were generally mild. Common grade 1/2 non-haematologic toxicities included transient transaminitis/alkaline phosphatase elevation (9 (37.5%) patients), nausea (9 (37.5%)), abdominal pain (7 (29.0%)), fatigue (7 (29.0%)), and hand-foot syndrome or rash/desquamation (7 (29.0%)). One patient experienced a partial gastric antral perforation with a capecitabine dose of 750 mg/m2. The best response was partial response in four (16.7%) patients, stable disease in 17 (70.8%) and progression in three (12.5%). Median time to progression and overall survival of the metastatic colorectal cancer cohort was 6.4 and 8.1 months, respectively.
Conclusions:
This combined modality treatment was generally well tolerated with encouraging clinical activity. Capecitabine 1000 mg/m2 b.i.d. is recommended for phase II study with sequential lobar radioembolization.
doi:10.1038/bjc.2014.344
PMCID: PMC4102951  PMID: 24983373
radioembolization; capecitabine; phase I
17.  Remodeling Cildb, a popular database for cilia and links for ciliopathies 
Cilia  2015;4(Suppl 1):P21.
doi:10.1186/2046-2530-4-S1-P21
PMCID: PMC4518628
19.  OFD1 and VFL3/CCDC61 in basal body positioning and docking in Paramecium 
Cilia  2015;4(Suppl 1):P29.
doi:10.1186/2046-2530-4-S1-P29
PMCID: PMC4518672
21.  Protection against Streptococcus pneumoniae lung infection after nasopharyngeal colonization requires both humoral and cellular immune responses 
Mucosal Immunology  2014;8(3):627-639.
Streptococcus pneumoniae is a common cause of pneumonia and infective exacerbations of chronic lung disease, yet there are few data on how adaptive immunity can specifically prevent S. pneumoniae lung infection. We have used a murine model of nasopharyngeal colonization by the serotype 19F S. pneumoniae strain EF3030 followed by lung infection to investigate whether colonization protects against subsequent lung infection and the mechanisms involved. EF3030 colonization induced systemic and local immunoglobulin G against a limited number of S. pneumoniae protein antigens rather than capsular polysaccharide. During lung infection, previously colonized mice had increased early cytokine responses and neutrophil recruitment and reduced bacterial colony-forming units in the lungs and bronchoalveolar lavage fluid compared with control mice. Colonization-induced protection was lost when experiments were repeated in B-cell- or neutrophil-deficient mice. Furthermore, the improved interleukin (IL)-17 response to infection in previously colonized mice was abolished by depletion of CD4+ cells, and prior colonization did not protect against lung infection in mice depleted of CD4+ cells or IL17. Together these data show that naturally acquired protective immunity to S. pneumoniae lung infection requires both humoral and cell-mediated immune responses, providing a template for the design of improved vaccines that can specifically prevent pneumonia or acute bronchitis.
doi:10.1038/mi.2014.95
PMCID: PMC4351900  PMID: 25354319
22.  The global threat of antimicrobial resistance: science for intervention 
In the last decade we have witnessed a dramatic increase in the proportion and absolute number of bacterial pathogens resistant to multiple antibacterial agents. Multidrug-resistant bacteria are currently considered as an emergent global disease and a major public health problem. The B-Debate meeting brought together renowned experts representing the main stakeholders (i.e. policy makers, public health authorities, regulatory agencies, pharmaceutical companies and the scientific community at large) to review the global threat of antibiotic resistance and come up with a coordinated set of strategies to fight antimicrobial resistance in a multifaceted approach. We summarize the views of the B-Debate participants regarding the current situation of antimicrobial resistance in animals and the food chain, within the community and the healthcare setting as well as the role of the environment and the development of novel diagnostic and therapeutic strategies, providing expert recommendations to tackle the global threat of antimicrobial resistance.
doi:10.1016/j.nmni.2015.02.007
PMCID: PMC4446399  PMID: 26029375
Antibiotic consumption; antibiotic resistance; antibiotic stewardship; antibiotics as growth promoters; drug discovery; infection control measures; multidrug resistant bacteria; self-medication; surveillance; wastewater treatment plants
23.  A Phenomenological One-Parameter Equation of State for Osmotic Pressures of PEG and Other Neutral Flexible Polymers in Good Solvents 
The journal of physical chemistry. B  2009;113(12):3709-3714.
We present a phenomenological one-parameter scaling equation of state that accurately represents osmotic pressures of neutral flexible polymers in good solvents from the dilute through the semidilute regime. The equation comprises a sum of scaled van’t Hoff and des Cloizeaux terms including a fitted parameter α, the “crossover index”, which encapsulates all chemical specificity and determines the relevant prefactors. Strikingly different values of α are found for the two very different systems poly(ethyleneglycol)/water (PEG) and poly(α-methylstyrene)/toluene (PAMS). α-dependent rescaling collapses both data sets to a simple one-parameter scaling function. The fact that the anomalous system PEG/water and the canonical system PAMS/toluene can both be described by the same equation of state attests to the robustness of the polymer-scaling concepts introduced by de Gennes.
doi:10.1021/jp806893a
PMCID: PMC4174303  PMID: 19265418
24.  The role of the humoral immune response to Clostridium difficile toxins A and B in susceptibility to Clostridium difficile Infection: a case-control study 
Anaerobe  2014;27:82-86.
Antibody levels to Clostridium difficile toxin A (TcdA), but not toxin B (TcdB), have been found to determine risk of C. difficile infection (CDI). Historically, TcdA was thought to be the key virulence factor; however the importance of TcdB in disease is now established. We re-evaluated the role of antibodies to TcdA and TcdB in determining patient susceptibility to CDI in two separate patient cohorts. In contrast to earlier studies, we find that CDI patients have lower pre-existing IgA titres to TcdB, but not TcdA, when compared to control patients. Our findings suggest that mucosal immunity to TcdB may be important in the early stages of infection and identifies a possible target for preventing CDI progression.
doi:10.1016/j.anaerobe.2014.03.011
PMCID: PMC4140433  PMID: 24708941
Clostridium difficile; toxin B (TcdB); toxin A (TcdA); Humoral immune response; case-control study
25.  Latino immigrants, discrimination and reception in Columbus, Ohio 
Columbus, Ohio has witnessed rapid growth in its Latino population as immigrants settle in the city to access jobs and a generally low cost of living. Immigrants also face discrimination as they settle in Columbus and interact with the city’s citizens. In this paper, we note how discrimination plays out in social and economic isolation; a lack of programs to support the incorporation of Latinos in the city; and state laws that target immigrants. We present results of ongoing ethnographic work with the Latino community in Columbus.
doi:10.1111/imig.12032
PMCID: PMC4119753  PMID: 25097268
Latinos Migration; Midwest US; Ohio; Discrimination; policy

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