Time series analysis of fMRI data: Spatial modelling and Bayesian computation

Time series analysis of fMRI data is an important area of medical statistics for neuroimaging data. Spatial models and Bayesian approaches for inference in such models have advantages over more traditional mass univariate approaches; however, a major challenge for such analyses is the required computation. As a result, the neuroimaging community has embraced approximate Bayesian inference based on mean‐field variational Bayes (VB) approximations. These approximations are implemented in standard software packages such as the popular statistical parametric mapping software. While computationally efficient, the quality of VB approximations remains unclear even though they are commonly used in the analysis of neuroimaging data. For reliable statistical inference, it is important that these approximations be accurate and that users understand the scenarios under which they may not be accurate. We consider this issue for a particular model that includes spatially varying coefficients. To examine the accuracy of the VB approximation, we derive Hamiltonian Monte Carlo (HMC) for this model and conduct simulation studies to compare its performance with VB in terms of estimation accuracy, posterior variability, the spatial smoothness of estimated images, and computation time. As expected, we find that the computation time required for VB is considerably less than that for HMC. In settings involving a high or moderate signal‐to‐noise ratio (SNR), we find that the 2 approaches produce very similar results suggesting that the VB approximation is useful in this setting. On the other hand, when one considers a low SNR, substantial differences are found, suggesting that the approximation may not be accurate in such cases and we demonstrate that VB produces Bayes estimators with larger mean squared error. A comparison of the 2 computational approaches in an application examining the hemodynamic response to face perception in addition to a comparison with the traditional mass univariate approach in this application is also considered. Overall, our work clarifies the usefulness of VB for the spatiotemporal analysis of fMRI data, while also pointing out the limitation of VB when the SNR is low and the utility of HMC in this case.     

Kinetics of antibody and memory B cell responses after MMR immunization in children and young adults

The persistence of antigen-specific memory B-cells (MBCs) in children and young adults long time after vaccination against measles, mumps and rubella (MMR) is not known. Here we have looked at the Swedish immunization program and examined children 1–10 years after the first MMR dose in early childhood, as well as young adults 7–18 years after the second dose of MMR. We show that Ab titers and MBCs against measles and rubella have different kinetics, indicating that the MBC pool and the corresponding Ab titers are regulated independently. These data fit well with other findings that continuous IgG secretion comes from long-lived plasma cells and not MBCs. We also demonstrate that individuals with low post-vaccination Ab titers might have an adequate MBC response. It remains to be shown if memory B-cells provide the same protection as specific antibodies, but our data is a valuable complement to the incomplete knowledge about correlates of protection after vaccination.     

Preoperative concurrent chemotherapy and radiation therapy in cervix cancer: preliminary results

This is a retrospective study of patients treated for cervix cancer staged IB2, IIA or IIB with bulky tumor (> 4cm). Treatment was concurrent radiotherapy (45Gy with 1,8Gy daily fraction) and chemotherapy (5 cycles of Platinum 40mg/m2/week). All patients underwent Brachytherapy (15Gy on the reference isodose according to Paris system) followed by surgery (radical abdominal hysterectomy and bilateral pelvic lymphadenectomy: Piver 3) Between October 1999 and December 2002, forty five patients were treated in this protocol. Median age was 46 years (21- 68). Histology was squamous cell carcinoma in 93% and glandular carcinoma in 7%. Average external radiation dose was 44Gy (20-50). Ninety three percent of patients had at least 3 cycles of chemotherapy and 46,5% received the planned 5 cycles. On the operative specimens, there was 62,5% complete response and only 7 pelvic node involvement (17,5%). Four postoperative complications were noted (one vascular injury, one urinary fistula, one phlebitis and one lymph collection). Preoperative combined radiotherapy and chemotherapy in the early bulky stages of uterine cervix cancer is well tolerated and "gives" a high rate of sterilisation. There was no increase in surgical morbidity.     

In vitro/in vivo evaluation of an optimized fast dissolving oral film containing olanzapine co-amorphous dispersion with selected carboxylic acids

Improvement of water solubility, dissolution rate, oral bioavailability, and reduction of first pass metabolism of OL (OL), were the aims of this research. Co-amorphization of OL carboxylic acid dispersions at various molar ratios was carried out using rapid solvent evaporation. Characterization of the dispersions was performed using differential scanning calorimetry (DSC), Fourier transform infrared spectrometry (FTIR), X-ray diffractometry (XRD), and scanning electron microscopy (SEM). Dispersions with highest equilibrium solubility were formulated as fast dissolving oral films. Modeling and optimization of film formation were undertaken using artificial neural networks (ANNs). The results indicated co-amorphization of OL-ascorbic acid through H-bonding. The co-amorphous dispersions at 1:2 molar ratio showed more than 600-fold increase in solubility of OL. The model optimized fast dissolving film prepared from the dispersion was physically and chemically stable, demonstrated short disintegration time (8.5?s), fast dissolution (97% in 10?min) and optimum tensile strength (4.9 N/cm²). The results of in vivo data indicated high bioavailability (144?ng h/mL) and maximum plasma concentration (14.2?ng/mL) compared with the marketed references. Therefore, the optimized co-amorphous OL-ascorbic acid fast dissolving film could be a valuable solution for enhancing the physicochemical and pharmacokinetic properties of OL.     

Towards nationwide control of schistosomiasis in Yemen: a pilot project to expand treatment to the whole community

Both the urinary and intestinal forms of schistosomiasis are thought to be widespread in the Republic of Yemen, with estimates of 3 million people infected and 600 000 suffering clinical morbidity. Sub-national control has been ongoing since 2006 via the distribution of praziquantel (PZQ) against schistosomiasis and albendazole (ALB) against soil-transmitted helminths using school-based treatment. In preparation for a 6-year nationwide control programme with the aim of expanding treatment to the wider community, a new programmatic approach of complementing school-based distribution with community-based treatment was trialled in 10 highly endemic districts in three governorates in December 2009. The new approach achieved coverage of 90.1% of non-enrolled children: a 40% increase compared with the same districts in 2008, and coverage of 97.9% of enrolled children: a 2% increase compared to 2008. Coverage of females (children and adults) was 81.8%, and of adults in general was 73.9%. The total cost per person treated was US$0.66 (US$0.79 in 2008), which includes training, health education, social mobilization, distribution and drugs. These results provide hope that a combined school and community-based approach can be successfully implemented on a wider scale during the main control programme in 2010-2015, with approximately 10 million people targeted in the first year alone.     

Coverage and side effects of influenza A(H1N1) 2009 monovalent vaccine among primary health care workers

In June 2009, WHO declared the maximum phase alert against H1N1 pandemic flu. Health care workers (HCWs) are considered a strategic target for prevention of the occurrence of H1N1 influenza since they had the greatest risk of acquiring infection. The objectives of our study were (1) identifying the uptake of influenza A(H1N1) 2009 monovalent vaccine by primary health care workers in the southern part of Cordoba, and (2) reporting of the adverse events occurred after vaccination. We followed 240 HCWs in 12 primary health care centres at southern part of Cordoba for vaccine uptake and the occurrence of adverse events. The coverage rate with H1N1 vaccine was 20.5% which was lower compared to seasonal influenza vaccination rate 44.2% in 2009. Males had higher H1N1 vaccination rate compared to females with no significant difference. Senior HCWs complied more with seasonal influenza vaccine while this finding was not consistent with H1N1 vaccination. Multivariate analysis showed that the only independent variable that affected H1N1 vaccine was the compliance to the seasonal flu vaccine in the past three years with OR 5.1 and 95% CI (2.4-10.8). Adverse events occurred among 26.5% of those who complied with H1N1 vaccination. Those were local pain, irritation and induration at site of injection (38.5%), fever (15.4%), fever cough and rhinorrhea (15.4%) generalized pain and lumber pains (23.1%). The low vaccination rate in this study is consistent with previous studies done in many parts of the world and in Spain. Further studies should be done to explore the factors that hindered the uptake and resistance of HCWs to vaccination to H1N1 vaccine.     

Regional Chemotherapy in Liver Metastases of Colorectal Carcinoma: Monitoring with Arterial Computed Tomography

Continuous chemotherapy was administered to 82 patients through the hepatic artery via Infusaid pumps. In order to obtain a primary status and to evaluate the success of therapy, the perfusion patterns of the liver and of the existing tumor masses in the liver were estimated by conducting arterial angiocomputed tomographies (AACTs) immediately after pump implantation of every 3 months thereafter. In 70% of the patients, findings showed both liver lobes to be homogeneously perfused, 24% demonstrated distinct inhomogeneities. The response of the latter cases should depend primarily on the efficacy of the administered cytostatic agent. Six percent of the patients showed selective perfusion of either the left or right hepatic lobe. In these cases, only me perfused liver regions exhibited stable disease or regression of the metastases, whereas the metastases of the nonperfused regions progressed. At 3-month follow-up, the majority of the patients (50-57%) showed homogeneous hepatic perfusion. Inhomogeneities were found in 26-36% of the patients, 12 patients demonstrated incomplete perfusion. There was no association between the perfusion patterns of the metastases or of the prechemotherapeutic liver involvement and the response of the metastases to regional chemotherapy. In regional chemotherapy, liver perfusion should be controlled both intraoperatively or directly postoperatively and during therapy.     

Biliary response to glucagon in humans.

Glucagon has been demonstrated to have profound effect on biliary secretion in several species. Glucagon's biliary effects were studied in humans following biliary tract surgery. Nine patients underwent common bile duct exploration and insertion of a balloon-occludable t tube. An aliquot of the collected sample was kept and the enterohepatic circulation was maintained by reinfusion of the collected bile via the distal t-tube port. Glucagon increased bile flow and decreased cholesterol and phospholipid output during stable bile acid output. Furthermore high-performance liquid chromatographic analysis of bile acid profiles revealed no significant changes in bile salt species or conjugation after glucagon infusion. Glucagon is probably important in the physiologic regulation of biliary secretion in humans.     

Cerebral regional oxygenation during aortic coarctation repair in pediatric population.

OBJECTIVE: During repair of aortic coarctation, clamping of the transverse aortic arch proximal to the left common carotid artery occludes blood flow to the left carotid and vertebral arteries. The objective of the present study is to determine whether blood flow through the right carotid and vertebral arteries provides adequate cerebral blood flow during aortic cross-clamping, as assessed by near-infrared spectroscopy. METHODS: In 11 consecutive children undergoing aortic coarctation repair through a standard posterolateral thoracotomy, regional cerebral oxygen saturation (cSO(2)) was measured using near-infrared spectroscopy. Six patients underwent an extended end-to-end repair, in which the aortic cross-clamp was placed in between the innominate and left common carotid arteries (extended repair group). Five patients underwent a standard end-to-end repair in which the cross-clamp was clamp placed between the left common carotid and subclavian arteries (standard repair group). RESULTS: After aortic clamping, there was a significant decrease in cSO(2) in the extended repair group, whereas the cSO(2) increased in the standard repair group (-9.2+/-12.2 vs 6.0+/-5.1%, extended vs standard repair groups, p=0.03). In the extended repair group, the cSO(2) decreased linearly during the aortic cross-clamping period (r(S)=-0.842, p<0.001), while in the standard repair group, the cSO(2) increased during the same time period (r(S)=0.786, p<0.001). Regression analysis identified the site of aortic cross-clamping as the sole independently significant variable explaining changes in the cSO(2) during aortic cross-clamping (p<0.03), whereas neither age nor duration of aortic cross-clamping was statistically significant. There were no postoperative neurological impairments in either group of patients. CONCLUSION: During aortic coarctation repair, aortic cross-clamping proximal, as compared to distal, to the left carotid artery is associated with significantly decreased regional cerebral oxygen saturation, as measured by near-infrared spectroscopy. Although no short-term clinical impairments were identified, long-term follow-up in a larger cohort is needed to study the effects of unbalanced cerebral oxygenation during clamping of the transverse arch. These data suggest that cerebral saturation monitoring is warranted, and may be indicative of cerebral hypoperfusion.