Formulation of a killed whole cell pneumococcus vaccine - effect of aluminum adjuvants on the antibody and IL-17 response

Background Streptococcus pneumoniae causes widespread morbidity and mortality. Current vaccines contain free polysaccharides or protein-polysaccharide conjugates, and do not induce protection against serotypes that are not included in the vaccines. An affordable and broadly protective vaccine is very desirable. The goal of this study was to determine the optimal formulation of a killed whole cell pneumococcal vaccine with aluminum-containing adjuvants for intramuscular injection. Methods Four aluminium-containing adjuvants were prepared with different levels of surface phosphate groups resulting in different adsorptive capacities and affinities for the vaccine antigens. Mice were immunized three times and the antigen-specific antibody titers and IL-17 responses in blood were analyzed. Results Although all adjuvants induced significantly higher antibody titers than antigen without adjuvant, the vaccine containing aluminum phosphate adjuvant (AP) produced the highest antibody response when low doses of antigen were used. Aluminum hydroxide adjuvant (AH) induced an equal or better antibody response at high doses compared with AP. Vaccines formulated with AH, but not with AP, induced an IL-17 response. The vaccine formulated with AH was stable and retained full immunogenicity when stored at 4°C for 4 months. Conclusions Antibodies are important for protection against systemic streptococcal disease and IL-17 is critical in the prevention of nasopharyngeal colonization by S. pneumoniae in the mouse model. The formulation of the whole killed bacterial cells with AH resulted in a stable vaccine that induced both antibodies and an IL-17 response. These experiments underscore the importance of formulation studies with aluminium containing adjuvants for the development of stable and effective vaccines

Positron emission tomography in the diagnostic work-up of screening-detected lung nodules

Low-dose computed tomography (CT) screening for lung cancer can reduce lung cancer mortality, but overdiagnosis, false positives and invasive procedures for benign nodules are worrying. We evaluated the utility of positron emission tomography (PET)-CT in characterising indeterminate screeningdetected lung nodules. 383 nodules, examined by PET-CT over the first 6 years of the COSMOS (Continuous Observation of Smoking Subjects) study to diagnose primary lung cancer, were reviewed and compared with pathological findings (surgically-treated patients) or follow-up (negative CT for â\u89¥2 years, considered negative); 196 nodules were malignant. The sensitivity, specificity and accuracy of PET-CT for differentially diagnosing malignant nodules were, respectively, 64%, 89% and 76% overall, and 82%, 92% and 88% for baseline-detected nodules. Performance was lower for nodules found at repeat annual scans, with sensitivity ranging from 22% for nonsolid to 79% for solid nodules (p=0.0001). Sensitivity (87%) and specificity (73%) were high for nodules â\u89¥15 mm, better (sensitivity 98%) for solid nodules â\u89¥15 mm. PET-CT was highly sensitive for the differential diagnosis of indeterminate nodules detected at baseline, nodules â\u89¥15 mm and solid nodules. Sensitivity was low for sub-solid nodules and nodules discovered after baseline for which other methods, e.g. volume doubling time, should be used

A short review of constructing noise map using crowdsensing technology

The advent of crowdsensing technology has provided a promising possibility for monitoring noise pollution in large-scale areas. Constructing noise map by using mobile smart phones in a cost-effective manner is being widely used in the city and industrial plants. In this short paper, the state-of-the-art crowdsensing-based noise map applications are first summarized. Furthermore, open research challenges associated with building up noise map are highlighted

Determinants of polyp Size in patients undergoing screening colonoscopy

<p>Abstract</p> <p>Background</p> <p>Pre-existing polyps, especially large polyps, are known to be the major source for colorectal cancer, but there is limited available information about factors that are associated with polyp size and polyp growth. We aim to determine factors associated with polyp size in different age groups.</p> <p>Methods</p> <p>Colonoscopy data were prospectively collected from 67 adult gastrointestinal practice sites in the United States between 2002 and 2007 using a computer-generated endoscopic report form. Data were transmitted to and stored in a central data repository, where all asymptomatic white (n = 78352) and black (n = 4289) patients who had a polyp finding on screening colonoscopy were identified. Univariate and multivariate analysis of age, gender, performance site, race, polyp location, number of polyps, and family history as risk factors associated with the size of the largest polyp detected at colonoscopy.</p> <p>Results</p> <p>In both genders, size of the largest polyp increased progressively with age in all age groups (<it>P </it>< .0001). In subjects ≥ 80 years the relative risk was 1.55 (95% CI, 1.35-1.79) compared to subjects in the youngest age group. With the exception of family history, all study variables were significantly associated with polyp size (<it>P </it>< .0001), with multiple polyps (≥ 2 versus 1) having the strongest risk: 3.41 (95% CI, 3.29-3.54).</p> <p>Conclusions</p> <p>In both genders there is a significant increase in polyp size detected during screening colonoscopy with increasing age. Important additional risk factors associated with increasing polyp size are gender, race, polyp location, and number of polyps, with polyp multiplicity being the strongest risk factor. Previous family history of bowel cancer was not a risk factor.</p

Ki-67 (30-9) scoring and differentiation of Luminal A- and Luminal B-like breast cancer subtypes

INTRODUCTION: Ki-67 labeling index assessed by immunohistochemical assays has been shown useful in assessing the risk of recurrence for estrogen receptor (ER)-positive HER2-negative breast cancers (BC) and distinguishing Luminal A-like from Luminal B-like tumors. We aimed to assess the performance of the Ventana CONFIRM anti-Ki-67 (30-9) Rabbit Monoclonal Primary Antibody. METHODS: We constructed a case-cohort design based on a random sample (n\u2009=\u2009679) of all patients operated on for a first primary, non-metastatic, ER-positive, HER2-negative BC at the European Institute of Oncology (IEO) Milan, Italy during 1998-2002 and all additional patients (n\u2009=\u2009303) operated during the same period, who developed an event (metastasis in distant organs or death due to BC as primary event) and were not included in the previous subset. Multivariable Cox proportional hazards regression with inverse subcohort sampling probability weighting was used to evaluate the risk of event according to Ki-67 (30-9) and derived intrinsic molecular subtype, using previously defined cutoff values, i.e., respectively 14% and 20%. RESULTS: Ki-67 was\u2009&lt;\u200914% in 318 patients (32.4%), comprised between 14 and 19% in 245 patients (24.9%) and\u2009 65\u200920 in 419 patients (42.7%). At multivariable analysis, the risk of developing distant disease was 1.88 (95% CI 1.20-2.93; P\u2009=\u20090.006) for those with Ki-67 comprised between 14 and 19%, and 3.06 (95% CI 1.93-4.84; P\u2009&lt;\u20090.0001) for those with Ki-67\u2009 65\u200920% compared to those with Ki-67\u2009&lt;\u200914%. Patients with Luminal B-like BC had an approximate twofold risk of developing distant disease (HR\u2009=\u20091.91; 95% CI 1.35-2.71; P\u2009=\u20090.0003) than patients with Luminal A-like BC defined using Ki-67 (30-9). CONCLUSIONS: Ki-67 evaluation using the 30-9 rabbit monoclonal primary antibody was able to stratify patients with ER-positive HER2-negative BC into prognostically distinct groups. Ki-67 assessment, with strict adherence to the international recommendations, should be included among the clinically useful biological parameters for the best treatment of patients with BC

Long-term outcomes of a pilot CT screening for lung cancer

Background: Low-dose computed tomography (CT) screening can detect early stage lung cancer in high-risk populations. However, no data on repeated annual screening over more than 5 years are available, and the impact of screening on lung cancer mortality is controversial. Methods: We analysed outcomes in high-risk asymptomatic volunteers (smokers and former smokers, >50 years) enrolled in a pilot study over 1 year from June 2000, who received annual low-dose CT for 7 years. Cumulative lung cancer incidence and survival were represented by Kaplan 12Meier curves. Standardized incidence and mortality ratios were used to estimate risks relative to the general Italian and US population. Results: Compliance was 86% at the end of the seventh year in 1035 recruited volunteers (71% men, mean age 58 years). Lung cancer was diagnosed in 54 (5.3%); radical surgery was possible in 48/54 (87%); 39/54 (72%) had stage I disease. Five-year survival was 63% overall, 89% for stage I cases. During 6308 person-years of observation, 47 participants had died versus 75 expected in the Italian general population standardised for age and sex. Fourteen lung cancer deaths were registered versus 27 expected in a standardised US smoker population. Conclusions: Seventy percent of screening-diagnosed patients had stage I disease, and the survival of screen-detected cancer patients was high. Lung cancer mortality was favourable compared to age- and sex-matched population of US smokers, suggesting that mortality can be lowered by screening, although larger trials with longer follow-up are necessary to confirm these findings

Case mix at the European Institute of Oncology: first report of the Tumour Registry, 2000–2002

Introduction: An institutional and centralized hospital-based tumour registry (TR) is the ideal supporting tool for the organization and management of clinical data in a comprehensive cancer centre. The purpose of this paper is to describe the development of the TR at the European Institute of Oncology (IEO) in Milan, Italy, from its origin to its current applications. Material and methods: After a series of meetings with members of administrative, clinical, research and informatics departments, the TR was activated in March 2006 with the aim to collect data on all the individuals referring to the Institute, with or at risk of developing a tumour. It was implemented on an Oracle\u2122-based interface. A minimum data set of variables was defined and data collection was divided into four forms, which together gather all the relevant data on patients, tumours, treatments and subsequent events. Results: After a 6-month pilot period, which involved the training of the tumour registrars, adjustments to the structure of the registry, development of data quality control procedure and finalization of the operative protocol, from September 2006 the data collection has been fully operative. Five registrars have been chronologically entering data of all individuals who visited the IEO for the first time since 1st January 2000. As of March 2009, data on 69,637 individuals and 43,567 tumours has been reviewed, recoded and registered in the TR. Twenty-two percent of the tumours (n=9,578) were first invasive primaries, diagnosed and treated in IEO; the most common sites were breast (n=4,972), lung (n=627), intestines (n=479) and prostate (n=376). Conclusion: The IEO TR has been proven functional and reliable in monitoring the activity of the Hospital, allowing extraction of data from any subpopulation with characteristics of interest. The structured and centralized TR represents an important tool for our research-oriented Institution

Spectroscopic Pulsational Frequency Identification and Mode Determination of Gamma Doradus Star HD135825

We present the mode identification of frequencies found in spectroscopic observations of the Gamma Doradus star HD135825. Four frequencies were successfully identified: 1.3150 +/- 0.0003 1/d; 0.2902 +/- 0.0004 1/d; 1.4045 +/- 0.0005 1/d; and 1.8829 +/- 0.0005 1/d. These correspond to (l, m) modes of (1,1), (2,-2), (4,0) and (1,1) respectively. Additional frequencies were found but they were below the signal-to-noise limit of the Fourier spectrum and not suitable for mode identification. The rotational axis inclination and vsini of the star were determined to be 87 degrees (nearly edge-on) and 39.7 km/s (moderate for Gamma Doradus stars) respectively. A simultaneous fit of these four modes to the line profile variations in the data gives a reduced chi square of 12.7. We confirm, based on the frequencies found, that HD135825 is a bona fide Gamma Doradus star.Comment: Accepted to MNRAS 2012 March

Survival of patients with HCV cirrhosis and sustained virologic response is similar to the general population.

Background &amp; Aims: Life expectancy of patients with compensated hepatitis C virus (HCV) cirrhosis achieving sustained virologic response (SVR) is limited by liver events as compared to the general population. Thus, survival benefit of SVR remains to be measured. Methods: The study includes prospective surveillance data from three cohorts of Italian patients with compensated HCV cirrhosis who achieved SVR on an interferon-based (IFN) regimen, compared to simultaneously observed non-SVR, untreated and decompensated patients. Overall survival was calculated from the date of start of IFN to death. The number of deaths expected during the at-risk period was determined by applying age- and sex-specific mortality rates recorded in Italy for person-years adequate for the enrolment period. The standardized mortality ratio (SMR) determined the relative risk of death over that of the age and sex matched general population. Results: Overall, 28/181 patients followed-up for a median period of 9.6 years (range 1–25 years) died. The 10 and 20-year overall survival rates for the whole series were 90.9% (95% CI, 84.3–94.8) and 62.9% (95% CI, 45.9–75.9), respectively. The number of expected deaths in the corresponding age and sex matched general population was 28.1, corresponding to a SMR = 1.00 (95% CI, 0.72–1.35), with an SMR for non-SVR patients of 3.85 (95% CI, 3.43–4.30), for untreated of 3.01 (95% CI, 2.64–3.42) and for decompensated of 6.70 (95% CI, 5.39–8.22). Conclusions: Patients with compensated HCV cirrhosis achieving SVR by IFN obtain a main benefit levelling their survival curve to that of the general population. Wider applicability of IFN-free regimens will possibly make this achievement more generalizable