Differences in the Cognitive Skills of Bonobos and Chimpanzees

While bonobos and chimpanzees are both genetically and behaviorally very similar, they also differ in significant ways. Bonobos are more cautious and socially tolerant while chimpanzees are more dependent on extractive foraging, which requires tools. The similarities suggest the two species should be cognitively similar while the behavioral differences predict where the two species should differ cognitively. We compared both species on a wide range of cognitive problems testing their understanding of the physical and social world. Bonobos were more skilled at solving tasks related to theory of mind or an understanding of social causality, while chimpanzees were more skilled at tasks requiring the use of tools and an understanding of physical causality. These species differences support the role of ecological and socio-ecological pressures in shaping cognitive skills over relatively short periods of evolutionary time

Plasma lipid profiles discriminate bacterial from viral infection in febrile children

Fever is the most common reason that children present to Emergency Departments. Clinical signs and symptoms suggestive of bacterial infection are often non-specific, and there is no definitive test for the accurate diagnosis of infection. The 'omics' approaches to identifying biomarkers from the host-response to bacterial infection are promising. In this study, lipidomic analysis was carried out with plasma samples obtained from febrile children with confirmed bacterial infection (n = 20) and confirmed viral infection (n = 20). We show for the first time that bacterial and viral infection produces distinct profile in the host lipidome. Some species of glycerophosphoinositol, sphingomyelin, lysophosphatidylcholine and cholesterol sulfate were higher in the confirmed virus infected group, while some species of fatty acids, glycerophosphocholine, glycerophosphoserine, lactosylceramide and bilirubin were lower in the confirmed virus infected group when compared with confirmed bacterial infected group. A combination of three lipids achieved an area under the receiver operating characteristic (ROC) curve of 0.911 (95% CI 0.81 to 0.98). This pilot study demonstrates the potential of metabolic biomarkers to assist clinicians in distinguishing bacterial from viral infection in febrile children, to facilitate effective clinical management and to the limit inappropriate use of antibiotics

Factors Associated with Revision Surgery after Internal Fixation of Hip Fractures

Background: Femoral neck fractures are associated with high rates of revision surgery after management with internal fixation. Using data from the Fixation using Alternative Implants for the Treatment of Hip fractures (FAITH) trial evaluating methods of internal fixation in patients with femoral neck fractures, we investigated associations between baseline and surgical factors and the need for revision surgery to promote healing, relieve pain, treat infection or improve function over 24 months postsurgery. Additionally, we investigated factors associated with (1) hardware removal and (2) implant exchange from cancellous screws (CS) or sliding hip screw (SHS) to total hip arthroplasty, hemiarthroplasty, or another internal fixation device. Methods: We identified 15 potential factors a priori that may be associated with revision surgery, 7 with hardware removal, and 14 with implant exchange. We used multivariable Cox proportional hazards analyses in our investigation. Results: Factors associated with increased risk of revision surgery included: female sex, [hazard ratio (HR) 1.79, 95% confidence interval (CI) 1.25-2.50; P = 0.001], higher body mass index (fo

Is FDG PET a Better Imaging Tool Than Somatostatin Receptor Scintigraphy in Patients With Relapsing Multiple Myeloma?

Purpose: Osseous involvement defined by lytic bone lesions is shown by skeletal survey in multiple myeloma (MM). This technique has limitations because it detects only lesions with more than 30% trabecular bone loss. In addition, lesions persist after chemotherapy, thereby limiting its usefulness at relapsing disease. Alternative techniques to detect new bone lesions are somatostatin receptor scintigraphy (SRS) and F-18-fluordeoxyglucose (FDG) PET so far predominantly studied in patients with newly diagnosed MM. Malignant plasma cells can have a high expression of somatostatin receptors and an elevated metabolic activity. Therefore, these techniques might be useful in patients with relapsing MM because they are not hampered by preexisting skeletal defects. The purpose of this study was to demonstrate which technique is most optimal to detect skeletal lesions in patients with relapsing MM. Method: In patients with relapsing MM (n = 21), 3 separate methods were used (skeletal survey, SRS, and FDG PET) for detecting new skeletal lesions. Results: Of all patients, 55% had new lesions on the skeletal survey [mean (SD), 1.45 (1.76); range, 0-5], 52% had new SRS lesions [mean (SD), 1.43 (0.38); range, 0-5], and 71% demonstrated new lesions on the FDG PET-scan [mean (SD), 4.05 (0.9); range, 0-12]. The lesions on skeletal survey and SRS corresponded with FDG PET. The number of lesions was higher with the FDG PET versus that with SRS (P = 0.01) and with FDG PET versus that with skeletal survey (P = 0.01). Conclusions: The results demonstrate that FDG PET is more valuable than skeletal survey and SRS to detect disease activity in relapsing MM

18F-FDG PET Increases Visibility of Bone Lesions in Relapsed Multiple Myeloma:Is This Hypoxia-Driven?

INTRODUCTION: Whole-body x-ray (WBX) is used for detecting skeleton abnormalities in patients with multiple myeloma (MM). An alternative might be F-FDG PET, which makes use of metabolic changes of malignant cells. The aims of this study were to evaluate whether F-FDG PET detects more lesions compared with WBX in patients with relapsing MM and to define its prognostic value. In addition 1-α-D: -(5-deoxy-5-[F]-fluoroarabinofuranosyl)-2-nitroimidazole (F-FAZA) scan and immunohistochemical staining on bone marrow were performed to define whether FDG uptake coincides with angiogenesis-related tumor hypoxia. PATIENTS AND METHODS: F-FDG PET (n = 44) and F-FAZA-PET (n = 5) were performed in patients with relapsed MM. Bone marrow biopsies (n = 20) were evaluated for hypoxia inducible factors (HIF) 1α and 2α, vascular endothelial growth factor, glucose transport proteins 1 and 3, and the microvessel density. RESULTS: New lesions were more frequently demonstrated on F-FDG PET than on WBX (P = 0.000001). F-FDG PET was not predictive for progression-free survival and overall survival. Immunohistochemical staining on bone marrow biopsies demonstrated a significant increase in microvessel density and elevated expression of vascular endothelial growth factor, HIF-2α, and glucose transport protein 3 by the malignant plasma cells. However, HIF-1α expression and F-FAZA scan results were negative. CONCLUSIONS: Our results demonstrate that F-FDG PET is relevant for diagnostic purposes compared with WBX in relapsing MM. The enhanced uptake of F-FDG PET is likely related to the activation of the HIF-2α signaling pathway but probably independent of hypoxia-induced signaling in view of the negative findings on both F-FAZA-PET and HIF-1α expression

Combination therapy with bortezomib, continuous low-dose cyclophosphamide and dexamethasone followed by one year of maintenance treatment for relapsed multiple myeloma patients

Combination therapy for longer periods but at low dose might be an effective and tolerable manner to treat patients with relapsed multiple myeloma (MM). We used bortezomib, dexamethasone and low-dose oral cyclophosphamide as an induction regimen, followed by 1 year of maintenance consisting of bortezomib and cyclophosphamide. Relapsed MM patients were treated with six cycles of bortezomib twice weekly, cyclophosphamide 50 mg daily and dexamethasone. Maintenance therapy was given for I year. Primary endpoints were toxicity during re-induction and maintenance therapy. Secondary endpoints were response to treatment and progression-free (PFS) and overall survival (OS). This study included 59 patients. Myclosuppression and neuropathy were the most common side effects. Median follow-up was 271 (0.46-54.4) months with an overall response of 71%, and a very good partial response or more of 33%. During maintenance, improved responsiveness was observed in 19% of the patients. The median PI'S was 18.4 months (range 0-13-43.5) and the median OS was 28.1 months (range 0.13-54.4). In conclusion, our study demonstrates that treatment with bortczomib, dexamethasone and low-dose cyclophosphamide is an effective and manageable regimen. Adding 1 year of maintenance was feasible, with limited side effects and an increased response rate

Thalidomide before and after autologous stem cell transplantation in recently diagnosed multiple myeloma (HOVON-50):long-term results from the phase 3, randomised controlled trial

Background: In patients with recently diagnosed multiple myeloma, the HOVON-50 phase 3 trial showed improved event-free survival for thalidomide-containing induction and maintenance regimens (in conjunction with high-dose melphalan and autologous stem cell transplantation [auto-SCT]) after a median of 52 months of follow-up, by comparison with regimens containing classical cytotoxic drugs. In this follow-up analysis, we aimed to determine the long-term effects of thalidomide in induction and maintenance therapy in multiple myeloma. Methods: In this open-label, phase 3 randomised controlled trial, patients with recently diagnosed multiple myeloma were recruited from 44 Dutch and Belgian hospitals. Participants had been diagnosed with multiple myeloma of Durie-Salmon stage II or III and were aged 18–65 years. Patients were randomly assigned (1:1) either to receive three 28-day cycles of vincristine (0·4 mg, intravenous rapid infusion on days 1–4), doxorubicin (9 mg/m2, intravenous rapid infusion on days 1–4) and dexamethasone (40 mg, orally on days 1–4, 9–12, and 17–20; control group); or to receive the same regimen, but with thalidomide (200–400 mg, orally on days 1–28) instead of vincristine (thalidomide group). No masking after assignment to intervention was used. Patients were randomly assigned to groups, stratified by centre and treatment policy (one vs two courses of high-dose melphalan and auto-SCT). After stem cell harvest, patients received one or two courses of 200 mg/m2 melphalan intravenously with auto-SCT. Patients with at least a partial response to high-dose melphalan and auto-SCT were eligible for maintenance therapy, starting 2–3 months after high-dose melphalan. Patients in the control group received maintenance therapy with interferon alfa (3 × 106 international units, subcutaneously, three times weekly). Patients in the thalidomide group received thalidomide as maintenance therapy (50 mg, orally, daily). Maintenance therapy was given until relapse, progression, or the occurrence of adverse events. The primary endpoint of the study was event-free survival (EFSc; censored at allogeneic stem cell transplantation), analysed by intention to treat. The study is closed for enrolment and this Article represents the final analysis. This trial was registered with the Netherlands Trial Register, number NTR238. Findings: Between Nov 27, 2001 and May 31, 2005, 556 patients were enrolled in the study, of whom 536 (96%) were eligible for evaluation and were randomly allocated (268 [50%] to the control group and 268 [50%] to the thalidomide group). These 536 patients were assessed for the primary endpoint of EFSc. At an extended median follow-up of 129 months (IQR 123–136), EFSc was significantly longer in the thalidomide group compared with the control group (multivariate analysis hazard ratio [HR] 0·62, 95% CI 0·50–0·77; p<0·0001). Thalidomide maintenance was stopped because of toxicity in 65 (42%) of 155 patients in the thalidomide group (neuropathy in 49 [75%] patients, skin reactions in four [6%] patients, fatigue in two [3%] patients, and as other symptoms [such as abdominal pain, pancreatitis, and dyspnoea] in ten [15%] patients). 24 (27%) of 90 patients in the control group discontinued protocol treatment during maintenance therapy with interferon alfa because of toxicity (five [21%] patients with psychiatric side-effects, five [21%] patients with flu-like symptoms, four [17%] patients with haematological toxicity [thrombocytopenia and leucocytopenia], three [13%] patients with skin reactions, and seven [29%] patients with other symptoms [such as infections, cardiomyopathy, and headache]). The frequency of second primary malignancies was similar in both groups. There were 23 second primary malignancies in 17 patients in the control group and 29 second primary malignancies in 24 patients in the thalidomide group. There were 19 treatment-related deaths in the control group, and 16 treatment-related deaths in the thalidomide group. Interpretation: Our data indicate that thalidomide-based treatment could be a treatment option for patients with multiple myeloma who are eligible for auto-SCT who live in countries without access to proteasome inhibitors or lenalidomide. However, careful follow-up and timely dose adjustments are important to prevent the development of thalidomide-induced neurotoxicity. Funding: The Dutch Cancer Foundation