Active Antigen-specific Immunotherapy of Melanoma: from Basic Science to Clinical Investigation

Advanced-stage melanoma here dismal prognosis, and novel therapeutic approaches are urgently required. The possibility of taking advantage of the immune response of patients for its treatment has been an appealing concept for almost a century. Only during the last decade, however, has the molecular identification of tumor-associated antigens (TAAs) offered the possibility of vaccinating patients (e.g., active induction of TAA-specific immune responses). Active antigen-specific immunotherapy (AASIT) is currently being investigated in a number of clinical centers as a treatment option for advanced-stage melanoma. A large number of melanoma TAAs have been molecularly characterized and are being used in vaccination trials in various molecular forms and according to various immunization protocols. Here we provide a short overview on melanoma TAAs, the technologies currently in use to induce specific cytotoxic T-lymphocyte (CTL) responses in vivo, and their monitoring. We also propose a tentative AASIT agenda for the next few years, aiming at improving the capacity to induce and monitor TAA-specific immune responses and to verify their clinical effectivenes

Autonomous interactive intermediaries : social intelligence for mobile communication agents

Thesis (Ph. D.)--Massachusetts Institute of Technology, School of Architecture and Planning, Program in Media Arts and Sciences, 2005.Includes bibliographical references (p. 151-167).Today's cellphones are passive communication portals. They are neither aware of our conversational settings, nor of the relationship between caller and callee, and often interrupt us at inappropriate times. This thesis is about adding elements of human style social intelligence to our mobile communication devices in order to make them more socially acceptable to both user and local others. I suggest the concept of an Autonomous Interactive Intermediary that assumes the role of an actively mediating party between caller, callee, and co-located people. In order to behave in a socially appropriate way, the Intermediary interrupts with non-verbal cues and attempts to harvest 'residual social intelligence' from the calling party, the called person, the people close by, and its current location. For example, the Intermediary obtains the user's conversational status from a decentralized network of autonomous body-worn sensor nodes. These nodes detect conversational groupings in real time, and provide the Intermediary with the user's conversation size and talk-to-listen ratio. The Intermediary can 'poll' all participants of a face-to-face conversation about the appropriateness of a possible interruption by slightly vibrating their wirelessly actuated finger rings.(cont.) Although the alerted people do not know if it is their own cellphone that is about to interrupt, each of them can veto the interruption anonymously by touching his/her ring. If no one vetoes, the Intermediary may interrupt. A user study showed significantly more vetoes during a collaborative group-focused setting than during a less group oriented setting. The Intermediary is implemented as a both a conversational agent and an animatronic device. The animatronics is a small wireless robotic stuffed animal in the form of a squirrel, bunny, or parrot. The purpose of the embodiment is to employ intuitive non-verbal cues such as gaze and gestures to attract attention, instead of ringing or vibration. Evidence suggests that such subtle yet public alerting by animatronics evokes significantly different reactions than ordinary telephones and are seen as less invasive by others present when we receive phone calls. The Intermediary is also a dual conversational agent that can whisper and listen to the user, and converse with a caller, mediating between them in real time.(cont.) The Intermediary modifies its conversational script depending on caller identity, caller and user choices, and the conversational status of the user. It interrupts and communicates with the user when it is socially appropriate, and may break down a synchronous phone call into chunks of voice instant messages.by Stefan Johannes Walter Marti.Ph.D

Accuracy of Frozen Section Analysis Versus Specimen Radiography During Breast-Conserving Surgery for Nonpalpable Lesions

Background: Whereas specimen radiography (SR) is an established strategy for intraoperative resection margin analysis during breast-conserving surgery for nonpalpable lesions, the use of frozen section analysis (FSA) is still a matter of debate. Methods: A retrospective review was conducted of 115 consecutive operations in which the two objectives sought were the excision of nonpalpable malignant lesions and breast conservation. Breast surgery was performed in the Gynecology and the Surgery Departments at the Basel University Hospital Breast Center. Whereas one department preferably uses SR for intraoperative margin assessments of lesions involving ductal carcinoma in situ (DCIS) or atypical ductal hyperplasia, the other uses FSA to increase the rate of complete removal of these lesions with a single procedure. The respective accuracy and therapeutic impact of these two techniques are compared here. Results: Intraoperative resection margin assessments were performed with FSA in 80 and SR in 35 of a total of 115 operations performed on 111 patients with pTis, pT1, or pT2 nonpalpable breast cancer. FSA diagnostic accuracy, sensitivity, and specificity were 83.8%, 80.0%, and 87.5%, respectively, compared to 60%, 60%, and 60%, respectively, for SR. FSA tended to have a stronger therapeutic impact than SR in terms of the number of patients in whom initially positive margins were rendered margin-negative thanks to intraoperative analysis and immediate reexcision or mastectomy (27.5% vs. 14.3%; p=0.124). More importantly, significantly fewer secondary reexcisions were performed in the FSA series than in the SR series (12.5% vs. 37.1%; p=0.002). Finally, the intraoperative detection of invasive cancer with FSA led to a significantly lower number of secondary procedures for axillary lymph node staging (5% vs. 25.7%; p=0.001). Conclusions: The present results suggest that FSA may be more accurate than SR for analyzing intraoperative resection margins during breast-conserving surgery for nonpalpable lesion

Mammotome: Less Invasive than ABBI with Similar Accuracy for Early Breast Cancer Detection

We performed a prospective analysis of two consecutive biopsy cohorts investigated by the same team to compare the Mammotome system with the ABBI procedure. From April 1997 to August 2003 a series of 413 nonpalpable mammographic lesions in 387 women (median age 56 years, range 30-84 years) were stereotactically biopsied in the University Hospital of Basel, Switzerland. Until October 1999 the ABBI system was applied exclusively, it was subsequently superseded by the Mammotome device in our clinic. Main outcome measures were accuracy, technical demand, and morbidity. Sensitivity (97.3%/96.8%), negative predictive value (99.2%/98.7%), and diagnostic accuracy (99.4%/99.1%) regarding the detection of malignancy were excellent for both techniques (ABBI/Mammotome). The Mammotome procedure was faster and less invasive, thus causing significantly less morbidity. The larger specimen obtained by the ABBI procedure resulted in more detailed histology. In conclusion, recommend the Mammotome system as the method of choice for detecting nonpalpable early breast cance

Successful Implementation of a Window for Routine Antimicrobial Prophylaxis Shorter than That of the World Health Organization Standard

Objective. To evaluate the feasibility of implementation of the refined window for routine antimicrobial prophylaxis (RAP) of 30-74 minutes before skin incision compared to the World Health Organization (WHO) standard of 0-60 minutes. Design. Prospective study on timing of routine antimicrobial prophylaxis in 2 different time periods. Setting. Tertiary referral university hospital with 30,000 surgical procedures per year. Methods. In all consecutive vascular, visceral, and trauma procedures, the timing was prospectively recorded during a first time period of 2 years (A; baseline) and a second period of 1 year (B; after intervention). An intensive intervention program was initiated after baseline. The primary outcome parameter was timing; the secondary outcome parameter was surgical site infection (SSI) rate in the subgroup of patients undergoing cholecystectomy/colon resection. Results. During baseline time period A (3,836 procedures), RAP was administered 30-74 minutes before skin incision in 1,750 (41.0%) procedures; during time period B (1,537 procedures), it was administered in 914 (56.0%; P < .001). The subgroup analysis did not reveal a significant difference in SSI rate. Conclusions. This bundle of interventions resulted in a statistically significant improvement of timing of RAP even at a shortened window compared to the WHO standar

Economic Burden of Surgical Site Infections at a European University Hospital

Objective. To quantify the economic burden of in-hospital surgical site infections (SSIs) at a European university hospital. Design. Matched case-control study nested in a prospective observational cohort study. Setting. Basel University Hospital in Switzerland, where an average of 28,000 surgical procedures are performed per year. Methods. All in-hospital occurrences of SSI associated with surgeries performed between January 1, 2000, and December 31, 2001, by the visceral, vascular, and traumatology divisions at Basel University Hospital were prospectively recorded. Each case patient was matched to a control patient by age, procedure code, and National Nosocomial Infection Surveillance System risk index. The case-control pairs were analyzed for differences in cost of hospital care and in provision of specialized care. Results. A total of 6,283 procedures were performed:187 SSIs were detected in inpatients, 168 of whom were successfully matched with a control patient. For case patients, the mean additional hospital cost was SwF19,638 (95% confidence interval [CI], SwF8,492-SwF30,784); the mean additional postoperative length of hospital stay was 16.8 days (95% CI, 13-20.6 days); and the mean additional in-hospital duration of antibiotic therapy was 7.4 days (95% CI, 5.1-9.6 days). Differences were primarily attributable to organ space SSIs (n = 76). Conclusions. Ina European university hospital setting, SSIs are costly and constitute a heavy and potentially preventable burden on both patients and healthcare provider

Factors affecting ammonium uptake in streams - an inter-biome perspective

The Lotic Intersite Nitrogen experiment (LINX) was a coordinated study of the relationships between North American biomes and factors governing ammonium uptake in streams. Our objective was to relate inter-biome variability of ammonium uptake to physical, chemical and biological processes. 2. Data were collected from 11 streams ranging from arctic to tropical and from desert to rainforest. Measurements at each site included physical, hydraulic and chemical characteristics, biological parameters, whole-stream metabolism and ammonium uptake. Ammonium uptake was measured by injection of \u275~-ammonium and downstream measurements of 15N-ammonium concentration. 3. We found no general, statistically significant relationships that explained the variability in ammonium uptake among sites. However, this approach does not account for the multiple mechanisms of ammonium uptake in streams. When we estimated biological demand for inorganic nitrogen based on our measurements of in-stream metabolism, we found good correspondence between calculated nitrogen demand and measured assimilative nitrogen uptake. 4. Nitrogen uptake varied little among sites, reflecting metabolic compensation in streams in a variety of distinctly different biomes (autotrophic production is high where allochthonous inputs are relatively low and vice versa). 5. Both autotrophic and heterotrophic metabolism require nitrogen and these biotic processes dominate inorganic nitrogen retention in streams. Factors that affect the relative balance of autotrophic and heterotrophic metabolism indirectly control inorganic nitrogen uptake