Early clinical drug product shelf-life setting using accelerated predictive stability and metabolite data for impurity qualification: A case study.

This case study demonstrates how knowledge of degradation products together with predictions can establish a lean stability strategy using the accelerated predictive stability (APS) principles. Applying all available data for AZD4831, (R)-1-(2-(1-aminoethyl)-4-chlorobenzyl)-2-thioxo-2,3-dihydro-1H-pyrrolo[3,2-d]pyrimidin-4(5H)-one, a reliable predictive model was developed despite minor differences in technical batch tablet compositions. Early forced degradation studies were performed to map potential degradation pathways.

In situ chamber for studying battery failure using high-speed synchrotron radiography.

The investigation of lithium-ion battery failures is a major challenge for personnel and equipment due to the associated hazards (thermal reaction, toxic gases and explosions). To perform such experiments safely, a battery abuse-test chamber has been developed and installed at the microtomography beamline ID19 of the European Synchrotron Radiation Facility (ESRF). The chamber provides the capability to robustly perform in situ abuse tests through the heat-resistant and gas-tight design for flexible battery geometries and configurations, including single-cell and multi-cell assemblies.

Dura Management Strategies in the Surgical Treatment of Adult Chiari Type I Malformation: A Retrospective, Multicenter, Population-Based Parallel Cohort Case Series.

Background: Symptomatic Chiari I malformation is treated with suboccipital decompression and C1 laminectomy. However, whether the dura should be opened (durotomy) or enlarged with a graft (duraplasty) remains unclear.

Objective: To compare outcomes in adult Chiari I malformation patients treated with duraplasty, durotomy, or without dural opening ("mini-decompression").

Case Report: Subtherapeutic Vancomycin and Meropenem Concentrations due to Augmented Renal Clearance in a Patient With Intracranial Infection Caused by .

occasionally causes brain abscesses that can be life-threatening, requiring prompt antibiotic and neurosurgical treatment. The source is often dental, and it may spread to the eye or the brain parenchyma. We report the case of a 34-year-old man with signs of apical periodontitis, endophthalmitis, and multiple brain abscesses caused by .

The blood endothelial cell chamber - An innovative system to study immune responses in drug development.

The risk for adverse immune-mediated reactions, associated with the administration of certain immunotherapeutic agents, should be mitigated early. Infusion reactions to monoclonal antibodies and other biopharmaceuticals, known as cytokine release syndrome, can arise from the release of cytokines via the drug target cell, as well as the recruitment of immune effector cells. While several in vitro cytokine release assays have been proposed up to date, many of them lack important blood components, required for this response to occur.

Controlling the performance of adhesive mixtures for inhalation using mixing energy.

A concept of mixing energy, ME, has been developed and applied to blending of adhesive mixtures for inhalation in a high shear blender. Six different systems were investigated, four of which included a coating agent. For blends containing a coating agent, it is shown that the applied ME is key to the control of two important functional mechanisms: i) coating of the carrier by the coating agent, and ii) the dispersibility of the active pharmaceutical ingredient (API).

Social and emotional contexts predict the development of gaze following in early infancy.

The development of gaze following begins in early infancy and its developmental foundation has been under heavy debate. Using a longitudinal design ( = 118), we demonstrate that attachment quality predicts individual differences in the onset of gaze following, at six months of age, and that maternal postpartum depression predicts later gaze following, at 10 months. In addition, we report longitudinal stability in gaze following from 6 to 10 months.

Quantification of surface composition and surface structure of inhalation powders using TOF-SIMS.

A multivariate TOF-SIMS methodology has been developed and applied to quantify surface composition and chemical distribution for dry powder blends. Surface properties are often critical to the behavior of powder formulations, especially in the case of dry powders for inhalation, as surface properties directly affect inter-particulate forces and, hence, the dispersibility of the formulation. The mass spectrum at each pixel was fit to a linear combination of reference spectra obtained by non-negatively constrained alternating least squares.

Hearing outcome after myringoplasty in Sweden: A nationwide registry-based cohort study.

Objectives: To present hearing results after successful primary myringoplasty surgeries registered in the Swedish Quality Registry for Myringoplasty and to evaluate the chance of hearing improvement and the risk of hearing loss.

Design: A retrospective nationwide cohort study based on prospectively collected registry data between 2002 and 2012.

Settings: Registry data from secondary and tertiary hospitals performing myringoplasty.

Robustness of a continuous direct compression line against disturbances in feeding.

The aim of the current study was to characterize the robustness of an integrated continuous direct compression (CDC) line against disturbances from feeding, i.e. impulses of API and short step disturbances.

The social foundation of executive function.

In this study, we propose that infant social cognition may 'bootstrap' the successive development of domain-general cognition in line with the cultural intelligence hypothesis. Using a longitudinal design, 6-month-old infants (N = 118) were assessed on two basic social cognitive tasks targeting the abilities to share attention with others and understanding other peoples' actions. At 10 months, we measured the quality of the child's social learning environment, indexed by parent's abilities to provide scaffolding behaviors during a problem-solving task.

Comparison between integrated continuous direct compression line and batch processing - The effect of raw material properties.

There is a current trend in pharmaceutical manufacturing to shift from traditional batch manufacture to continuous manufacturing. The purpose of this study was to test the ability of an integrated continuous direct compression (CDC) line, in relation to batch processing, to achieve consistent tablet quality over long processing periods for formulations with poor flow properties or with a tendency to segregate. The study design included four industrially relevant formulations with different segregation indices and flow properties induced through different grades of the Active Pharmaceutical Ingredient (API), paracetamol, and major filler as well as varying the amount of API.

Percutaneous absorption of thirty-eight organic solvents in vitro using pig skin.

Percutaneous absorption is highly variable between chemicals but also within chemicals depending on exposure conditions and experimental set up. We tested a larger number of organic solvents with the same experimental set up, using skin from new-born piglets and static diffusion cells. Thirty-six common organic solvents were studied neat (and 31 of them also in water dilution): acetone, acetonitrile, n-butanol 2-butanone 2-butoxyethanol, 1-butoxy-2-propanol, n-butyl acetate, butyl acrylate, cyclohexane, cyclohexanone, 1,2-dichloroethane, dichloromethane, ethanol, 2-ethoxyethanol, ethyl acetate, ethyl acrylate, ethylbenzene, furfuryl alcohol, n-hexane, 2-hexanone, 2-isopropoxyethanol, methanol, 1-methoxy-2-propanol, methyl acrylate, 3-methyl-1-butanol, methyl tertiary butyl ether, 4-metyl-2-pentanol, methyl methacrylate, 2-propanol, 2-propen-1-ol, 2-propoxyethanol, 1-propoxy-2-propanol, styrene, trichloromethane, toluene and m-xylene.

Tinnitus and taste disturbances reported after myringoplasty: Data from a national quality registry.

Objectives/hypothesis: Postoperative tinnitus and taste disturbances after myringoplasty are more common than previously reported.

Study Design: This study was a retrospective analysis of prospectively collected data from the Swedish National Quality Registry for Myringoplasty.

Methods: The analysis was performed on extracted data from all counties in Sweden collected from database A from 2002 to 2012 and database B from 2013 to 2016.

Provoking an end-to-end continuous direct compression line with raw materials prone to segregation.

Continuous manufacturing of solid oral dosage forms is promising for increasing the efficiency and quality of pharmaceutical production and products. In this study a whole train continuous direct compression (CDC) line has been provoked using challenging formulations typically prone to segregation in batch powder processing. Industrial compositions including components with variable size, bulk density and cohesive nature were selected.

The role of sustained attention, maternal sensitivity, and infant temperament in the development of early self-regulation.

This study investigated infant predictors of early cognitive and emotional self-regulation from an intrinsic and caregiving environmental perspective. Sustained attention, reactive aspects of infant temperament, and maternal sensitivity were assessed at 10 months (n = 124) and early self-regulation (including executive functions, EF, and emotion regulation) was assessed at 18 months. The results indicated that sustained attention predicted early EF, which provide empirical support for the hierarchical framework of EF development, advocating early attention as a foundation for the development of cognitive self-regulation.

Myringoplasty Outcomes From the Swedish National Quality Registry.

Objectives/hypothesis: Data from patients registered for myringoplasty during 2002 to 2012 in the Swedish National Quality Registry for Myringoplasty.

Study Design: Both conventional myringoplasty and fat-graft techniques were used aimed at healing the tympanic membrane in noninfected ears.

Methods: Analysis was performed on data in a national database collected from 32 ear, nose, and throat clinics.

Maternal Sensitivity in Mothers with Mild Intellectual Disabilities is Related to Experiences of Maltreatment and Predictive of Child Attachment: A Matched-Comparison Study.

Background: Scientific knowledge on the quality of caregiving/maternal sensitivity among mothers with mild intellectual disabilities (ID) is limited and subject to many methodological shortcomings, but seems to suggest that these mothers are less sensitive than mothers without intellectual disabilities.

Methods: In this matched-comparison study (N = 48), the present authors observed maternal sensitivity for 20 min in four different laboratory play situations. The study also included semi-structured interviews to assess maternal experiences of maltreatment and child attachment.

Long-term sensory disturbances after orbitozygomatic fractures.

Background: Orbitozygomatic fractures often lead to infraorbital nerve (ION) injury, and affected sensibility is a common long-term complaint within this patient group. We present a long-term follow-up study where the validated von Frey filament system was used for testing ION sensibility. Furthermore, we examined the incidence of persistent nerve injury and whether more complex fractures led to more pronounced ION sensibility disturbances.

Achieving a robust drug release from extended release tablets using an integrated continuous mixing and direct compression line.

In the present work the viability of integrated continuous mixing and compression processes for manufacturing of extended release (ER) matrix tablets was investigated in terms of dissolution behavior. The purpose was also to evaluate the combined effect of processing variables and compositional variables on the release robustness. The continuous process was provoked by a challenging formulation design, including variable powder characteristics and compositions of high and low amount of poorly soluble and poorly flowing drug substance (ibuprofen).

Prior participation in the strange situation and overstress jointly facilitate disorganized behaviours: implications for theory, research and practice.

We seek to understand why a relatively high percentage (39%; vs the meta-analytic average, 15-18%) of disorganized/disoriented (D) classifications has accrued in the low-risk Uppsala Longitudinal Study (ULS) study, using experienced D coders. Prior research indicates that D behaviours do not always indicate attachment disorganization stemming from a history of frightening caregiving. We examined the role of two other presumed factors: participation in a previous strange situation and overstress.

Is middle childhood attachment related to social functioning in young adulthood?

The aim of the present study (N = 69) was to examine whether middle childhood attachment, measured using the Separation Anxiety Test (Slough, Goyette & Greenberg, 1988), predicts aspects of social functioning (social initiative, prosocial orientation, social anxiety, loneliness) in young adulthood. Insecurity-avoidance at age 8.5 years was, as expected, negatively related to social initiative and prosocial orientation, and was also positively related to social anxiety and loneliness at age 21 years.

Mesenchymal stromal cells support endothelial cell interactions in an intramuscular islet transplantation model.

Background: Mesenchymal stromal cells (MSC) have been under investigation for a number of therapies and have lately been in focus as immunosuppressive actors in the field of transplantation. Herein we have extended our previously published in vitro model of MSC-islets in an experimental setting of islet transplantation to the abdominal muscle. Human islets coated with luciferase-GFP transduced human MSC were transplanted to the abdomen muscle tissue of NOD-scid ILR2γ(null) mice and cellular interactions were investigated by confocal microscopy.

Continuous manufacturing of extended release tablets via powder mixing and direct compression.

The aim of the current work was to explore continuous dry powder mixing and direct compression for manufacturing of extended release (ER) matrix tablets. The study was span out with a challenging formulation design comprising ibuprofen compositions with varying particle size and a relatively low amount of the matrix former hydroxypropyl methylcellulose (HPMC). Standard grade HPMC (CR) was compared to a recently developed direct compressible grade (DC2).