Disorder and dissolution enhancement: deposition of ibuprofen on to insoluble polymers.

Microcrystalline cellulose (MCC) and cross-linked polyvinylpyrrolidone (PVP-CL) were examined as polymeric carriers to support amorphous ibuprofen (IB). Drug/carrier systems were prepared as physical mixes, and drug was loaded onto the polymers by hot mix and solvent deposition methods. The systems were examined using differential scanning calorimetry (DSC), X-ray powder diffractometry (XRD) and by dissolution testing. PVP-CL reduced drug crystallinity more than MCC and, surprisingly, even very simple mixing of ibuprofen with PVP-CL induced disordering of the drug. Increased ibuprofen dissolution rates were achieved with both polymers, in the order of solvent deposition>hot mixes>physical mixes. The increased dissolution rates could be attributed to a combination of faster dissolution from amorphous ibuprofen, microcrystalline drug deposition on carrier surfaces and polymer swelling. However, no clear relationship was observed between ibuprofen dissolution rates (using first order, Higuchi or Hixson-Crowell relationships) and drug crystallinity.     

Timing of CMF chemotherapy in combination with tamoxifen in postmenopausal women with breast cancer: role of endocrine responsiveness of the tumor.

BACKGROUND: Controversy persists about whether chemotherapy benefits all breast cancer patients. PATIENTS AND METHODS: In the International Breast Cancer Study Group (IBCSG) trial VII, 1212 postmenopausal patients with node-positive disease were randomized to receive tamoxifen for 5 years or tamoxifen plus three concurrent courses of cyclophosphamide, methotrexate and 5-fluorouracil ('classical' CMF) chemotherapy, either early, delayed or both. In IBCSG trial IX, 1669 postmenopausal patients with node-negative disease were randomized to receive either tamoxifen alone or three courses of adjuvant classical CMF prior to tamoxifen. Results were assessed according to estrogen receptor (ER) content of the primary tumor. RESULTS: For patients with node-positive, ER-positive disease, adding CMF either early, delayed or both reduced the risk of relapse by 21% (P=0.06), 26% (P=0.02) and 25% (P=0.02), respectively, compared with tamoxifen alone. There was no difference in disease-free survival when CMF was given prior to tamoxifen in patients with node-negative, ER-positive tumors. CONCLUSIONS: CMF given concurrently (early, delayed or both) with tamoxifen was more effective than tamoxifen alone for patients with node-positive, endocrine-responsive breast cancer, supporting late administration of chemotherapy even after commencement of tamoxifen. In contrast, sequential CMF and tamoxifen for patients with node-negative, endocrine-responsive disease was ineffective.     

IFPA Gabor Than Award lecture: Molecular control of placental growth: The emerging role of microRNAs

Fetal growth is dependent on appropriate growth and function of the placenta. This is modulated by a variety of factors, including maternal growth factors that exert their actions by binding to specific receptors on trophoblast to promote activation of signaling events. Kinases and phosphatases within trophoblast act in concert to regulate growth factor actions and recent studies have begun to elucidate a role for microRNAs (miRs) in regulating the levels of these proteins in the placenta. This review will discuss growth factor signaling in the placenta and describe the emerging role of miRs in regulating placental development.     

Reduced Mimicry to Virtual Reality Avatars in Autism Spectrum Disorder

Mimicry involves unconsciously copying the actions of others. Increasing evidence suggests that autistic people can copy the goal of an observed action but show differences in their mimicry. We investigated mimicry in autism spectrum disorder (ASD) within a two-dimensional virtual reality environment. Participants played an imitation game with a socially engaged avatar and socially disengaged avatar. Despite being told only to copy the goal of the observed action, autistic participants and matched neurotypical participants mimicked the kinematics of the avatars’ movements. However, autistic participants mimicked less. Social engagement did not modulate mimicry in either group. The results demonstrate the feasibility of using virtual reality to induce mimicry and suggest mimicry differences in ASD may also occur when interacting with avatars.     

Time Since Death: A Novel Approach to Dating Skeletal Remains

Criminal investigators dealing with skeletal remains have the primary concern for determining whether the remains are of anthropological or archaeological interest. If the remains are determined to be from an anthropological era, the next concern becomes the determination of time since death (TSD). Despite advances in modern technology, TSD remains a most elusive determinant. It has critical value for providing police with a time frame in which the person may have gone missing, increasing the likelihood of a positive identification. This article outlines a novel approach to dating skeletal remains in an Australian context, but with global connotations.     

Sources of Poor Performance on the Rey–Osterrieth Complex Figure Test among Children With Learning Difficulties: A Dynamic Assessment Approach

A dynamic assessment approach was used to examine the source of poor performance on the Rey–Osterrieth Complex Figure Test (ROCF) among 202 school-age children referred for learning difficulties. The ROCF was administered in the standard format and then in a structured format that highlighted the designs organizational framework. Manipulating encoding in this way improved recall to at least age-level for the majority of children. Those children who did not benefit from the structured format had relatively poor visual organizational skills. For most children with learning problems, poor ROCF performance stems from metacognitive difficulties; for a minority, the source appears to be more perceptual. A dynamic assessment procedure can enhance the diagnostic utility of the ROCF for children.     

A vanguard randomised feasibility trial comparing three regimens of peri-operative oxygen therapy on recovery after major surgery

International recommendations encourage liberal administration of oxygen to patients having surgery under general anaesthesia, ostensibly to reduce surgical site infection. However, the optimal oxygen regimen to minimise postoperative complications and enhance recovery from surgery remains uncertain. The hospital operating theatre randomised oxygen (HOT-ROX) trial is a multicentre, patient- and assessor-blinded, parallel-group, randomised clinical trial designed to assess the effect of a restricted, standard care, or liberal peri-operative oxygen therapy regimen on days alive and at home after surgery in adults undergoing prolonged non-cardiac surgery under general anaesthesia. Here, we report the findings of the internal vanguard feasibility phase of the trial undertaken in four large metropolitan hospitals in Australia and New Zealand that included the first 210 patients of a planned overall 2640 trial sample, with eight pre-specified endpoints evaluating protocol implementation and safety. We screened a total of 956 participants between 1 September 2019 and 26 January 2021, with data from 210 participants included in the analysis. Median (IQR [range]) time-weighted average intra-operative F_iO₂ was 0.30 (0.26–0.35 [0.20–0.59]) and 0.47 (0.44–0.51 [0.37–0.68]) for restricted and standard care, respectively (mean difference (95%CI) 0.17 (0.14–0.20), p < 0.001). Median time-weighted average intra-operative F_iO₂ was 0.83 (0.80–0.85 [0.70–0.91]) for liberal oxygen therapy (mean difference (95%CI) compared with standard care 0.36 (0.33–0.39), p < 0.001). All feasibility endpoints were met. There were no significant patient adverse events. These data support the feasibility of proceeding with the HOT-ROX trial without major protocol modifications.