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Kevin P Cole, Jennifer McClary Groh, Martin D Johnson, Christopher L Burcham, Bradley M Campbell, William D Diseroad, Michael R Heller, John R Howell, Neil J Kallman, Thomas M Koenig, Scott A May, Richard D Miller, David Mitchell, David P Myers, Steven S Myers, Joseph L Phillips, Christopher S Polster, Timothy D White, Jim Cashman, Declan Hurley, Robert Moylan, Paul Sheehan, Richard D Spencer, Kenneth Desmond, Paul Desmond, Olivia Gowran
Advances in drug potency and tailored therapeutics are promoting pharmaceutical manufacturing to transition from a traditional batch paradigm to more flexible continuous processing. Here we report the development of a multistep continuous-flow CGMP (current good manufacturing practices) process that produced 24 kilograms of prexasertib monolactate monohydrate suitable for use in human clinical trials. Eight continuous unit operations were conducted to produce the target at roughly 3 kilograms per day using small continuous reactors, extractors, evaporators, crystallizers, and filters in laboratory fume hoods...
June 16, 2017: Science
Tove Porseryd, Kristina Volkova, Nasim Reyhanian Caspillo, Thomas Källman, Patrik Dinnetz, Inger Porsh Hällström
The synthetic estrogen 17α-ethinylestradiol (EE2) is an endocrine disrupting compound of concern due to its persistence and widespread presence in the aquatic environment. Effects of developmental exposure to low concentrations of EE2 in fish on reproduction and behavior not only persisted to adulthood, but have also been observed to be transmitted to several generations of unexposed progeny. To investigate the possible biological mechanisms of the persistent anxiogenic phenotype, we exposed zebrafish embryos for 80 days post fertilization to 0, 3, and 10 ng/L EE2 (measured concentrations 2...
2017: Frontiers in Behavioral Neuroscience
Hans-Erik Källman, Rickard Holmberg, Jonas Andersson, Love Kull, Erik Tranéus, Anders Ahnesjö
PURPOSE: Radiation dose to patients undergoing examinations with Multislice Computed Tomography (MSCT) as well as Cone Beam Computed Tomography (CBCT) is a matter of concern. Risk management could benefit from efficient replace rational dose calculation tools. The paper aims to verify MSCT dose calculations using a Treatment Planning System (TPS) for radiotherapy and to evaluate four different variations of bow-tie filter characterizations for the beam model used in the dose calculations...
November 2016: Medical Physics
N Nand, R Mittal, M Yadav, S Venu, A R Deshmukh
Kallman syndrome (KS) is a rare genetic disorder characterized clinically by failure to attain puberty or failure to fully complete it along with an absent or impaired sense of smell with absence of bilateral olfactory bulbi and sulci alongwith absent olfactory tracts. Only very few cases of Kallman syndrome have been reported in females in Indian population.
October 2016: Journal of the Association of Physicians of India
Christian H Roux, Violaine Foltz, Emmanuel Maheu, Gabriel Baron, Frederique Gandjbakhch, Cédric Lukas, Daniel Wendling, Damien Loeuille, Pierre Lafforgue, Liana Euler-Ziegler, Pascal Richette, Xavier Chevalier
OBJECTIVES: To explore the relationship between clinical findings, biologic biomarkers, conventional radiography and MRI in patients with painful hand OA. METHODS: The following patient baseline data from the DORA study (evaluating anti-TNF-α agents against painful hand OA) were used: clinical assessment (pain, swelling, stiffness and function: Dreiser functional hand index [FIHOA] and Cochin hand functional scale [CHFS]); measurement of biomarkers (cartilage oligomeric matrix protein (COMP), type IIA collagen N-propeptid (PIINP), hyaluronic acid (HA), ultrasensitive C-reactive protein (usCRP), tumour necrosis factor (TNF), interleukin (IL)-6, IL-1β and urinary CTXII); radiological staging (Verbruggen, Kallman, Kellgren-Lawrence); anatomical evaluation by contrast-enhanced MRI of proximal and distal interphalangeal joints of dominant hand...
November 2016: Clinical and Experimental Rheumatology
David V Gauvin, Zachary J Zimmermann, Mary Jeanne Kallman
BACKGROUND: The Controlled Substances Staff of the Center for Drug Evaluation and Research at the US Food and Drug Administration and the Pharmaceutical Research Manufacturers Association (PhRMA) conducted a series of open forum dialog sessions between 2006 and 2016. A Cross Company Abuse Liability Council (CCALC) was formed during the process of this unique collaborative effort between Industry and Federal Regulators whose goals were to establish the development of standards for the preclinical screening of new molecular entities for schedule control actions required as part of every New Drug Application process...
August 13, 2016: Drug and Alcohol Dependence
Ulrika Källman, Sara Bergstrand, Anna-Christina Ek, Maria Engström, Margareta Lindgren
OBJECTIVES: To describe individual blood flow responses in a nursing home resident population for one-hour periods of bed rest. METHODS: Blood flow was measured for one hour over the sacrum in 0° supine position and 30° supine tilt position in 25 individuals aged 65 years or older while lying on a pressure-redistributing mattress. Measurements were made at three tissue depths (1, 2 and 10 mm) using the non-invasive optical techniques LDF and PPG. RESULTS: Eleven participants had a pressure-induced vasodilation (PIV) response at 1 mm depth in both positions and seven participants had a lack of this response at this depth and positions...
August 17, 2016: Microcirculation: the Official Journal of the Microcirculatory Society, Inc
Meiyuan Guo, Erik Källman, Lasse Kragh Sørensen, Mickaël G Delcey, Rahul V Pinjari, Marcus Lundberg
For first-row transition metals, high-resolution 3d electronic structure information can be obtained using resonant inelastic X-ray scattering (RIXS). In the hard X-ray region, a K pre-edge (1s→3d) excitation can be followed by monitoring the dipole-allowed Kα (2p→1s) or Kβ (3p→1s) emission, processes labeled 1s2p or 1s3p RIXS. Here the restricted active space (RAS) approach, which is a molecular orbital method, is used for the first time to study hard X-ray RIXS processes. This is achieved by including the two sets of core orbitals in different partitions of the active space...
July 28, 2016: Journal of Physical Chemistry. A
Louise Brousseau, Dragos Postolache, Martin Lascoux, Andreas D Drouzas, Thomas Källman, Cristina Leonarduzzi, Sascha Liepelt, Andrea Piotti, Flaviu Popescu, Anna M Roschanski, Peter Zhelev, Bruno Fady, Giovanni Giuseppe Vendramin
BACKGROUND: Local adaptation is a key driver of phenotypic and genetic divergence at loci responsible for adaptive traits variations in forest tree populations. Its experimental assessment requires rigorous sampling strategies such as those involving population pairs replicated across broad spatial scales. METHODS: A hierarchical Bayesian model of selection (HBM) that explicitly considers both the replication of the environmental contrast and the hierarchical genetic structure among replicated study sites is introduced...
2016: PloS One
Jonas Nilsson, Mikael Källman, Ulrika Östlund, Georg Holgersson, Michael Bergqvist, Stefan Bergström
BACKGROUND: Complementary alternative medicine (CAM) is widely used among patients with cancer. This usage may have potentially harmful effects, especially when combined with anticancer drugs. However, some complementary methods may benefit patients. This review investigated the prevalence of CAM use among patients with cancer in Scandinavia and secondly studied the educational levels of CAM users compared to non-users. MATERIALS AND METHODS: A systematic search of the PubMed library was carried out to locate articles published between January 2000 and October 2015 that investigated prevalence of CAM use among Scandinavian patients with cancer...
July 2016: Anticancer Research
Miguel Nemesio-Gorriz, Almuth Hammerbacher, Katarina Ihrmark, Thomas Källman, Åke Olson, Martin Lascoux, Jan Stenlid, Jonathan Gershenzon, Malin Elfstrand
Despite the fact that fungal diseases are a growing menace for conifers in modern silviculture, only a very limited number of molecular markers for pathogen resistance have been validated in conifer species. A previous genetic study indicated that the resistance of Norway spruce (Picea abies) to Heterobasidion annosum s.l., a pathogenic basidiomycete species complex, is linked to a quantitative trait loci that associates with differences in fungal growth in sapwood (FGS) that includes a gene, PaLAR3, which encodes a leucoanthocyanidin reductase...
August 2016: Plant Physiology
Xingui Liu, Nan Bai, Xiangdong Kong
OBJECTIVE: To explore the pathogenesis of a patient featuring azoospermia and steroid sulfatase deficiency. METHODS: Polymerase chain reaction (PCR), G-banded karyotyping and Illumina Human CytoSNP-12 Beadchip analysis were conducted. RESULTS: STS sites PCR showed that there was no deletion in the AZF zone. G-banding analysis indicated an unknown structural change in chromosome X, which was verified by single nucleotide polymorphism array (SNP array) as a 5...
June 2016: Zhonghua Yi Xue Yi Chuan Xue za Zhi, Zhonghua Yixue Yichuanxue Zazhi, Chinese Journal of Medical Genetics
Simon Authier, Joseph Arezzo, Marcus S Delatte, Mary-Jeanne Kallman, Carrie Markgraf, Dominique Paquette, Michael K Pugsley, Sian Ratcliffe, William S Redfern, Joanne Stevens, Jean-Pierre Valentin, Hugo M Vargas, Michael J Curtis
The Safety Pharmacology Society (SPS) conducted an industry survey in 2015 to identify industry practices as they relate to central, peripheral and autonomic nervous system ('CNS') drug safety testing. One hundred fifty-eight (158) participants from Asia (16%), Europe (20%) and North America (56%) responded to the survey. 52% of participants were from pharmaceutical companies (>1000 employees). Oncology (67%) and neurology/psychiatry (66%) were the most frequent target indications pursued by companies followed by inflammation (48%), cardiovascular (43%), metabolic (39%), infectious (37%), orphan (32%) and respiratory (29%) diseases...
September 2016: Journal of Pharmacological and Toxicological Methods
Anders Ahlsson, Örjan Friberg, Jan Källman
INTRODUCTION: Cat bite infections usually involve a mix of anaerobic and aerobic bacteria including species of Pasteurella, Streptococcus, Staphylococcus, Bacteroides, and Fusobacterium. We report a case of Pasteurella multocida infection from cat bites leading to endocarditis and subsequent aortic valve replacement. PRESENTATION OF CASE: A 70-year-old male was admitted because of fever, tachycardia, and malaise. He had a history of alcohol abuse and was living alone with a cat in a rural area...
2016: International Journal of Surgery Case Reports
Jun Chen, Thomas Källman, Xiao-Fei Ma, Giusi Zaina, Michele Morgante, Martin Lascoux
The joint inference of selection and past demography remain a costly and demanding task. We used next generation sequencing of two pools of 48 Norway spruce mother trees, one corresponding to the Fennoscandian domain, and the other to the Alpine domain, to assess nucleotide polymorphism at 88 nuclear genes. These genes are candidate genes for phenological traits, and most belong to the photoperiod pathway. Estimates of population genetic summary statistics from the pooled data are similar to previous estimates, suggesting that pooled sequencing is reliable...
2016: G3: Genes—Genomes—Genetics
Anna Kyndel, Caroline Elmér, Owe Källman, Daniel Altman
OBJECTIVES: To determine if Mycoplasma genitalium, Ureaplasma urealyticum, and Ureaplasma parvum are more common in premenopausal women with urethral pain syndrome than in asymptomatic controls. METHODS: We used a case-control study design to compare the prevalence of M. genitalium, U. urealyticum, and U. parvum using polymerase chain reaction (PCR) analysis in urine. Urethral pain syndrome was defined as localized urethral pain with or without accompanying lower urinary tract symptoms during the past month or longer and at least one negative urine culture...
July 2016: Journal of Lower Genital Tract Disease
Jamil Zaki, Seth Kallman, G Elliott Wimmer, Kevin Ochsner, Daphna Shohamy
Neuroscientific studies of social cognition typically employ paradigms in which perceivers draw single-shot inferences about the internal states of strangers. Real-world social inference features much different parameters: People often encounter and learn about particular social targets (e.g., friends) over time and receive feedback about whether their inferences are correct or incorrect. Here, we examined this process and, more broadly, the intersection between social cognition and reinforcement learning. Perceivers were scanned using fMRI while repeatedly encountering three social targets who produced conflicting visual and verbal emotional cues...
September 2016: Journal of Cognitive Neuroscience
Sara Cajander, Elisabet Tina, Anders Bäckman, Anders Magnuson, Kristoffer Strålin, Bo Söderquist, Jan Källman
INTRODUCTION: A decrease in the expression of monocyte surface protein HLA-DR (mHLA-DR), measured by flow cytometry (FCM), has been suggested as a marker of immunosuppression and negative outcome in severe sepsis. However, FCM is not always available due to sample preparation that limits its use to laboratory operational hours. In this prospective study we evaluated dynamic changes in mHLA-DR expression during sepsis in relation to changes in HLA-DRA gene expression and Class II transactivator (CIITA), measured by quantitative Real-Time Polymerase Chain Reaction (qRT-PCR)...
2016: PloS One
Yoshiaki Tsuda, Jun Chen, Michael Stocks, Thomas Källman, Jørn Henrik Sønstebø, Laura Parducci, Vladimir Semerikov, Christoph Sperisen, Dmitry Politov, Tiina Ronkainen, Minna Väliranta, Giovanni Giuseppe Vendramin, Mari Mette Tollefsrud, Martin Lascoux
Boreal species were repeatedly exposed to ice ages and went through cycles of contraction and expansion while sister species alternated periods of contact and isolation. The resulting genetic structure is consequently complex, and demographic inferences are intrinsically challenging. The range of Norway spruce (Picea abies) and Siberian spruce (Picea obovata) covers most of northern Eurasia; yet their geographical limits and histories remain poorly understood. To delineate the hybrid zone between the two species and reconstruct their joint demographic history, we analysed variation at nuclear SSR and mitochondrial DNA in 102 and 88 populations, respectively...
June 2016: Molecular Ecology
Simon Authier, Marcus S Delatte, Mary-Jeanne Kallman, Joanne Stevens, Carrie Markgraf
Electroencephalogram (EEG) data in nonclinical species can play a critical role in the successful evaluation of a compound during drug development, particularly in the evaluation of seizure potential and for monitoring changes in sleep. Yet, while non-invasive electrocardiogram (ECG) monitoring is commonly included in preclinical safety studies, pre-dose or post-dose EEG assessments are not. Industry practices as they relate to preclinical seizure liability and sleep assessments are not well characterized and the extent of preclinical EEG testing varies between organizations...
September 2016: Journal of Pharmacological and Toxicological Methods
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