Granular retrosplenial cortex layer 2/3 generates high-frequency oscillations dynamically coupled with hippocampal rhythms across brain states.

The granular retrosplenial cortex (gRSC) exhibits high-frequency oscillations (HFOs; ∼150 Hz), which can be driven by a hippocampus-subiculum pathway. How the cellular-synaptic and laminar organization of gRSC facilitates HFOs is unknown. Here, we probe gRSC HFO generation and coupling with hippocampal rhythms using focal optogenetics and silicon-probe recordings in behaving mice. ChR2-mediated excitation of CaMKII-expressing cells in L2/3 or L5 induces HFOs, but spontaneous HFOs are found only in L2/3, where HFO power is highest. HFOs couple to CA1 sharp wave-ripples (SPW-Rs) during rest and the descending phase of theta. gRSC HFO current sources and sinks are the same for events during both SPW-Rs and theta oscillations. Independent component analysis shows that high gamma (50-100 Hz) in CA1 stratum lacunosum moleculare is comodulated with HFO power. HFOs may thus facilitate interregional communication of a multisynaptic loop between the gRSC, hippocampus, and medial entorhinal cortex during distinct brain and behavioral states.

T-DOpE probes reveal sensitivity of hippocampal oscillations to cannabinoids in behaving mice.

Understanding the neural basis of behavior requires monitoring and manipulating combinations of physiological elements and their interactions in behaving animals. We developed a thermal tapering process enabling fabrication of low-cost, flexible probes combining ultrafine features: dense electrodes, optical waveguides, and microfluidic channels. Furthermore, we developed a semi-automated backend connection allowing scalable assembly. We demonstrate T-DOpE (Tapered Drug delivery, Optical stimulation, and Electrophysiology) probes achieve in single neuron-scale devices (1) high-fidelity electrophysiological recording (2) focal drug delivery and (3) optical stimulation. The device tip can be miniaturized (as small as 50 µm) to minimize tissue damage while the ~20 times larger backend allows for industrial-scale connectorization. T-DOpE probes implanted in mouse hippocampus revealed canonical neuronal activity at the level of local field potentials (LFP) and neural spiking. Taking advantage of the triple-functionality of these probes, we monitored LFP while manipulating cannabinoid receptors (CB1R; microfluidic agonist delivery) and CA1 neuronal activity (optogenetics). Focal infusion of CB1R agonist downregulated theta and sharp wave-ripple oscillations (SPW-Rs). Furthermore, we found that CB1R activation reduces sharp wave-ripples by impairing the innate SPW-R-generating ability of the CA1 circuit.

Granular retrosplenial cortex layer 2/3 generates high-frequency oscillations coupled with hippocampal theta and gamma in online states or sharp-wave ripples in offline states.

Neuronal oscillations support information transfer by temporally aligning the activity of anatomically distributed 'writer' and 'reader' cell assemblies. High-frequency oscillations (HFOs) such as hippocampal CA1 sharp-wave ripples (SWRs; 100-250 Hz) are sufficiently fast to initiate synaptic plasticity between assemblies and are required for memory consolidation. HFOs are observed in parietal and midline cortices including granular retrosplenial cortex (gRSC). In 'offline' brain states (e.g. quiet wakefulness) gRSC HFOs co-occur with CA1 SWRs, while in 'online' states (e.g. ambulation) HFOs persist with the emergence of theta oscillations. The mechanisms of gRSC HFO oscillations, specifically whether the gRSC can intrinsically generate HFOs, and which layers support HFOs across states, remain unclear. We addressed these issues in behaving mice using optogenetic excitation in individual layers of the gRSC and high density silicon-probe recordings across gRSC layers and hippocampus CA1. Optogenetically induced HFOs (iHFOs) could be elicited by depolarizing excitatory neurons with 100 ms half-sine wave pulses in layer 2/3 (L2/3) or layer 5 (L5) though L5 iHFOs were of lower power than in L2/3. Critically, spontaneous HFOs were only observed in L2/3 and never in L5. Intra-laminar monosynaptic connectivity between excitatory and inhibitory neurons was similar across layers, suggesting other factors restrict HFOs to L2/3. To compare HFOs in online versus offline states we analyzed, separately, HFOs that did or did not co-occur with CA1 SWRs. Using current-source density analysis we found uniform synaptic inputs to L2/3 during all gRSC HFOs, suggesting layer-specific inputs may dictate the localization of HFOs to L2/3. HFOs occurring without SWRs were aligned with the descending phase of both gRSC and CA1 theta oscillations and were coherent with CA1 high frequency gamma oscillations (50-80 Hz). These results demonstrate that gRSC can internally generate HFOs without rhythmic inputs and that HFOs occur exclusively in L2/3, coupled to distinct hippocampal oscillations in online versus offline states.

Youth Perspectives on the Effects of a Family-centered Media Literacy Intervention to Encourage Healthier Eating.

A pretest-posttest field test with control group (N = 189 parent-child dyads) tested a structural model representing youths' (ages 9-14) perspectives to examine the efficacy of a family-centered, media literacy-oriented intervention promoting fruit and vegetable consumption. The intervention facilitated critical discussion about nutrition and media, mentored by the parent. Results showed that youths' increases in fruit and vegetable consumption flowed from parent-child discussion of nutrition labels, which was predicted by child-initiated discussion, critical thinking about media sources, and critical thinking about media content. Multivariate analyses revealed that the intervention was productive for all participating age groups and for all dependent variables. The results suggest that a developmental progression from critical thinking about source to critical thinking about content affects behavior change and can be catalyzed through media literacy education and encouragement to discuss media messages (i.e. practice) with parents.

Effects of Family-Centered Media Literacy Training on Family Nutrition Outcomes.

Parents frustrated about food marketing influences need media management skills to challenge marketing messages and interpret factual content. We tested a media literacy-based, family-centered intervention to reduce effects of appealing, but unrealistic, food marketing. We hypothesized that participation would facilitate family discussion that improves the home dietary environment and increases youth consumption of fruits and vegetables. Parent-child (age 9-14) dyads (N = 189) participated in a matched-group, pretest/posttest field experiment testing a 6-week media literacy-based curriculum. Hypothesis testing employed multiple analysis of covariance and Bayesian multigroup structural equation modeling (MGSEM). Improved nutrition outcomes for parents included talk with youth about food nutrition labels (d = 0.343) and ratio of healthy to unhealthy food in home (d = 0.232); youth improved talk with parent about food nutrition labels (d = 0.211), vegetables eaten yesterday (d = 0.264), and fruit eaten yesterday (d = 1.386). Bayesian MGSEM revealed that in the intervention group, 12 of 17 tested paths were significant (p < .05), compared with only 4 in the control group, with average effect size magnitudes of 0.236 and 0.113, respectively. Media literacy education can empower parents and improve youths' critical thinking to reduce negative effects of food marketing on families and improve use of media to obtain nutrition information that aids dietary choices. This approach reduces the risk for reactance from youth who like media and resist limiting media use, while helping families use media together to make better nutrition decisions.

Realizing the "40 by 2022" Commitment from the United Nations High-Level Meeting on the Fight to End Tuberculosis: What Will It Take to Meet Rapid Diagnostic Testing Needs?

The potential gains from full adoption of World Health Organization (WHO)-recommended rapid diagnostics (WRDs) for tuberculosis (TB) are significant, but there is no current analysis of the additional investment needed to reach this goal. We sought to estimate the necessary investment in instruments, tests, and money, using Xpert MTB/RIF (Xpert), which detects Mycobacterium tuberculosis (MTB) and tests for resistance to rifampicin (RIF), as an example. An existing calculator for TB diagnostic needs was adapted to estimate the Xpert needs for a group of 24 countries with high TB burdens. This analysis assumed that countries will achieve the case-finding commitments agreed to at the recent United Nations High-Level Meeting on the Fight to End Tuberculosis, and that countries would adopt the WHO-recommended algorithm in which all people with signs and symptoms of TB receive an Xpert test. When compared to the current investments in these countries, this baseline model revealed that countries would require a 4-fold increase in the number of Xpert modules and a 6-fold increase in the number of Xpert test cartridges per year to meet their full testing needs. The incremental cost of the additional instruments for these countries would total approximately US$474 million, plus an incremental cost each year of cartridges of approximately $586 million, or a 5-fold increase over current investments. A sensitivity analysis revealed a variety of possible changes under alternative scenarios, but most of these changes either do not meet the global goals, are unrealistic, or would result in even greater investment needs. These findings suggest that a major investment is needed in WRD capacity to implement the recommended diagnostic algorithm for TB and reach the case-finding commitments by 2022.

The influence of chronic kidney disease on the duration of hospitalisation and transfusion rate after elective hip and knee arthroplasty.

PURPOSE: Elective hip or knee replacement is an optimal, standardised orthopaedic surgical procedure. The influence of chronic kidney disease, defined as an estimated glomerular filtration rate (eGFR) of 15-45 ml/min/1.73 m2 body surface area (BSA) (KDIGO stage G3a-G4), on the duration of hospitalisation, perioperative decrease in haemoglobin (Hb) levels, and transfusion rates after orthopaedic procedures has not been fully clarified. Our study, therefore, aimed to evaluate the impact of chronic kidney disease on the previously mentioned variables. METHODS: We conducted a retrospective multicentre analysis involving two orthopaedic centres. Patients who underwent elective total hip and knee replacement between 2010 and 2015 were included. We used descriptive methods and multivariate linear and binary regression analyses for our statistical evaluations. RESULTS: We evaluated 3301 datasets (1120 men [33.9%], 2181 women [66.1%], 2043 [61.9%], and 1258 [38.1%]) elective total hip and knee replacements, respectively. The following variables were identified as risk factors for a prolonged hospital stay: patient age, admission Hb and potassium levels, perioperative Hb level decrease, year of surgery, blood transfusion, and a preoperative eGFR of 15-45 ml/min/m2 BSA. Patients with an eGFR of > 45 ml/min/m2 BSA were discharged within 11.7 ± 3.0 days, while patients with an eGFR of 15-45 ml/min/1.73 m2 BSA remained inpatient for 13.5 ± 5.0 days (p < 0.001). Identified risk factors for postoperative blood transfusions included age, initial Hb level, perioperative Hb decrease, prosthetic hip replacement, and the presence of allergic diathesis. Blood transfusions were performed in 7.5% of patients with an eGFR of > 45 ml/min/m2 BSA compared to 24.1% of patients with an eGFR of 15-45 ml/min/1.73 m2 BSA (p < 0.001). An eGFR level of 15-45 ml/min/m2 BSA was identified as a risk factor for a postoperative decrease in Hb levels. CONCLUSION: Chronic kidney disease, defined as an eGFR level of 15-45 ml/min/1.73 m2 BSA, was a risk factor for a prolonged hospital stay after elective hip and knee arthroplasty. Further studies are necessary to better define the effect of reduced kidney function on relevant clinical and socioeconomic outcome parameters.

Clash of the Primary Motivations: Motivated Processing of Emotionally Experienced Content in Fear Appeals About Obesity Prevention.

This study examined individuals' physiological and cognitive responses to different types of emotionally experienced content located in obesity prevention fear appeals. Results suggested that experienced valence impacted individuals' attention and memory as a function of experienced arousal level. Local content that created coactive highly arousing experiences received the most attention, though visual recognition suggested these messages were more difficult to encode. Local content that created negative moderately arousing experiences was best encoded. Global message evaluation data suggest that moderately arousing messages with a change in experienced valence may prove to be most effective, as they ensure attention and good memory while keeping high self-reported interest, and a high level of perceived severity of obesity. Implications and suggestions for future research are discussed.

Atezolizumab in platinum-treated locally advanced or metastatic urothelial carcinoma: post-progression outcomes from the phase II IMvigor210 study.

BACKGROUND: Conventional criteria for tumor progression may not fully reflect the clinical benefit of immunotherapy or appropriately guide treatment decisions. The phase II IMvigor210 study demonstrated the efficacy and safety of atezolizumab, a programmed death-ligand 1-directed antibody, in patients with platinum-treated locally advanced or metastatic urothelial carcinoma. Patients could continue atezolizumab beyond Response Evaluation Criteria In Solid Tumors (RECIST) v1.1 progression at the investigator's discretion: this analysis assessed post-progression outcomes in these patients. PATIENTS AND METHODS: Patients were treated with atezolizumab 1200 mg i.v. every 3 weeks until loss of clinical benefit. Efficacy and safety outcomes in patients who experienced RECIST v1.1 progression and did, or did not, continue atezolizumab were analyzed descriptively. RESULTS: In total, 220 patients who experienced progression from the overall cohort (n = 310) were analyzed: 137 continued atezolizumab for ≥ 1 dose after progression, 19 received other systemic therapy, and 64 received no further systemic therapy. Compared with those who discontinued, patients continuing atezolizumab beyond progression were more likely to have had a baseline Eastern Cooperative Oncology Group performance status of 0 (43.1% versus 31.3%), less likely to have had baseline liver metastases (27.0% versus 41.0%), and more likely to have had an initial response to atezolizumab (responses in 11.7% versus 1.2%). Five patients (3.6%) continuing atezolizumab after progression had subsequent responses compared with baseline measurements. Median post-progression overall survival was 8.6 months in patients continuing atezolizumab, 6.8 months in those receiving another treatment, and 1.2 months in those receiving no further treatment. Atezolizumab exposure-adjusted adverse event frequencies were generally similar before and following progression. CONCLUSION: In this single-arm study, patients who continued atezolizumab beyond RECIST v1.1 progression derived prolonged clinical benefit without additional safety signals. Identification of patients most likely to benefit from atezolizumab beyond progression remains an important challenge in the management of metastatic urothelial carcinoma. CLINICALTRIALS.GOV ID: NCT02108652.

Aspiration and dysphagia screening in acute stroke - the Gugging Swallowing Screen revisited.

BACKGROUND AND PURPOSE: The Gugging Swallowing Screen (GUSS) is a tool to screen aspiration risk in acute stroke. We aimed to replicate its validity in a larger second cohort of patients with acute stroke, including the more severe with a National Institutes of Health Stroke Scale (NIHSS) ≥ 15. METHODS: In a prospective, double-blind design, the GUSS was validated with the Fiberoptic Endoscopic Evaluation of Swallowing scale. Patients were categorized into different stroke severities as assessed by the NIHSS, and the diagnostic properties were calculated separately for each subgroup. RESULTS: A total of 100 patients with acute stroke were evaluated consecutively at a mean 1.7 ± 2.2 days after stroke. With the GUSS cut-off value of 14 points, the GUSS screened aspiration risk with a 96.5% sensitivity and 55.8% specificity (area under the curve, 0.76; 95% CI, 0.67-0.84), which corresponded well with the original publication. In the NIHSS < 5 group, the sensitivity and specificity levels were 71.4% and 88.8%, respectively. In the NIHSS ≥ 15 group, these levels changed to 100% and 20%, respectively. The high failure rate in completing the first part of the GUSS in the latter group was related to the low specificity. Diet recommendations following the GUSS were more conservative than those after Fiberoptic Endoscopic Evaluation of Swallowing. In particular, the GUSS overestimated the need for nasogastric tube feeding. CONCLUSIONS: This is the first time that a swallowing screening tool for patients with acute stroke has been revalidated in a larger population from another stroke center. The validity of a swallow screening test may vary according to different stroke severities.

Plasmonic modulator with >170 GHz bandwidth demonstrated at 100 GBd NRZ.

We demonstrate a plasmonic Mach-Zehnder (MZ) modulator with a flat frequency response exceeding 170 GHz. The modulator comprises two phase modulators exploiting the Pockels effect of an organic electro-optic material in plasmonic slot waveguides. We further show modulation at 100 GBd NRZ and 60 GBd PAM-4. The electrical drive signals were generated using a 100 GSa/s digital to analog converter (DAC). The high-speed and small-scale devices are relevant for next-generation optical interconnects.

Detection of Chlamydia pneumoniae in a collection of captive snakes and response to treatment with marbofloxacin.

In a collection of 58 snakes comprising predominantly Eurasian vipers in Switzerland, five snakes died unexpectedly during hibernation from 2009 to 2012. In one snake, organisms resembling chlamydiae were detected by immunohistochemistry in multiple histiocytic granulomas. Real-time quantitative PCR and microarray analysis were used to determine the presence of Chlamydia pneumoniae in tissue samples and cloacal/choanal swabs from snakes in the collection; 8/53 (15.1%) of the remaining snakes were positive. Although one infected snake had suppurative periglossitis, infection with C. pneumoniae did not appear to be associated with specific clinical signs in snakes. Of seven snakes treated with 5 mg/kg marbofloxacin IM once daily, five became PCR negative for C. pneumoniae following treatment, whereas one animal remained positive and one snake was lost to follow-up.

(18) F-FDG PET/CT for initial staging in breast cancer patients - Is there a relevant impact on treatment planning compared to conventional staging modalities?

OBJECTIVE: To evaluate the impact of whole-body (18) F-FDG PET/CT on initial staging of breast cancer in comparison to conventional staging modalities. METHODS: This study included 102 breast cancer patients, 101 patients were eligible for evaluation. Preoperative whole-body staging with PET/CT was performed in patients with clinical stage ≥ T2 tumours or positive local lymph nodes (n = 91). Postoperative PET/CT was performed in patients without these criteria but positive sentinel lymph node biopsy (n = 10). All patients underwent PET/CT and a conventional staging algorithm, which included bone scan, chest X-ray and abdominal ultrasound. PET/CT findings were compared to conventional staging and the impact on therapeutic management was evaluated. RESULTS: PET/CT led to an upgrade of the N or M stage in overall 19 patients (19 %) and newly identified manifestation of breast cancer in two patients (2 %). PET/CT findings caused a change in treatment of 11 patients (11 %). This is within the range of recent studies, all applying conventional inclusion criteria based on the initial T and N status. CONCLUSIONS: PET/CT has a relevant impact on initial staging and treatment of breast cancer when compared to conventional modalities. Further studies should assess inclusion criteria beyond the conventional T and N status, e.g. tumour grading and receptor status. KEY POINTS: • PET/CT may be relevant in staging breast cancer patients at higher risk for metastases • PET/CT may modify the N and M stage in multiple patients • PET/CT may impact treatment planning in breast cancer patients.

[Value of galactography for the diagnostic work-up of pathological nipple discharge in multimodal breast diagnostics. Part 2: a systematic review of the literature]. / Stellenwert der Galaktographie zur Abklärung pathologischer Sekretion in der komplementären Mammadiagnostik. Teil 2: Eine systematische Literaturanalyse.

BACKGROUND: The survey results of a previous study showed that galactography is now rarely used in Germany and newer methods are applied. The evidential value of galactography should be established and opposed to the evidential value of ultrasound (US) and magnetic resonance mammography (MRM). MATERIALS AND METHODS: A search was carried out in PubMed and Cochrane involving studies written in English or German. The level of evidence was measured according to the Oxford Centre for Evidence-based Medicine. RESULTS: A total of 19 studies were included, 14 with results on galactography, 10 on US and 5 on MRM. Almost all studies were retrospective with an evidence assigned to level 3b or lower. The results on the diagnostic values showed a very wide range. Because of very variable numbers of cases and consideration of various pathologies, the studies are only comparable to a limited extent. CONCLUSION: Galactography, US and MRM all show a weak level of evidence and no superiority of a particular method can be derived. Therefore, galactography can no longer be considered as a mandatory standard in modern multimodal imaging of the breast. Recommendations for the diagnostic work-up of pathological nipple discharge have to be included in current guidelines and must consider these facts.

[Value of galactography for the diagnostic work-up of pathological nipple discharge in multimodal breast diagnostics : Part 1: An online survey among German breast care centers.] / Stellenwert der Galaktographie zur Abklärung pathologischer Sekretion in der komplementären Mammadiagnostik : Teil 1: Eine Onlineumfrage an den deutschen Brustzentren.

PURPOSE: Galactography has been used in cases of pathological discharge for decades. Meanwhile other methods, such as high-resolution ultrasound (US) and magnetic resonance mammography (MRM) have been established for modern multimodal breast imaging. A survey among certified German breast care centers aimed to investigate to what extent galactography is currently used and whether newer techniques in multimodal imaging are preferred. MATERIALS AND METHODS: An anonymous online survey was carried out nationwide and open to 342 radiology units in certified German breast care centers. RESULTS: A total of 177 units (52 %) participated in the survey of which 13 % generally do not provide galactography, 33 % conduct a maximum of 5 galactographies per year, 24 % conduct 6-10, 18 % 11-20, 8 % 21-50 and 5 % 51-100. Of the participants 53 % give first priority to US and prefer galactography to MRM in stepwise diagnosis and 32 % prefer MRM to galactography. Only 4 % use galactography initially. CONCLUSION: Currently galactography is no longer a mandatory standard and newer methods are preferred. The evidential value of galactography in comparison to other techniques should be established on the basis of the literature. The second part of this paper will deal with this question.

Improved two-year outcomes after drug-eluting versus bare-metal stent implantation in women and men with large coronary arteries: importance of vessel size.

OBJECTIVES: To investigate the importance of vessel size on outcome differences by comparing the effects of drug-eluting stents (DES) versus bare-metal stents (BMS) in women and men with large coronary vessels. METHODS: All 2314 BASKET-PROVE patients randomized to DES versus BMS were followed for 2 years with a primary endpoint of major adverse cardiac events (MACE: cardiac death, non-fatal myocardial infarction, target-vessel revascularization). Cox proportional hazard models were used to evaluate the relative risk for women and men, respectively. All comparisons were adjusted for vessel size. RESULTS: Age, risk factors and complexity of coronary artery disease differed between women and men. DES reduced MACE rates at 2 years compared to BMS--in women: 4% vs. 15%, p<0.0001 with a hazard ratio (HR) of 0.27 (0.15-0.51), and men: 6% vs. 10%, p=0.003 (HR=0.60 (0.43-0.84)), respectively. The association persisted in both women (HR=0.25 (0.13-0.46)) and men (HR=0.60 (0.42-0.84)) following multivariable adjustments. A significant gender-treatment interaction was present (p=0.02). The reduced risk of MACE following DES vs. BMS implantation was present until 6 months in both women (HR=0.15 (0.06-0.36)) and men (HR=0.32 (0.17-0.59)) and remained significant until 2 years in women (HR=0.36 (0.15-0.87)), but not in men (HR=0.87 (0.49-1.55)). CONCLUSIONS: In women and men with similarly sized large coronary arteries, DES reduced 2-year MACE rates compared to BMS, but the significant gender-treatment interaction indicated a greater benefit of DES in women. Thus, factors other than vessel size seem to determine this gender difference.

Axillary lymph node characterization in breast cancer patients using magnetic resonance mammography: a prospective comparative study with FDG PET-CT and healthy women.

OBJECTIVE: The aim of this study was to evaluate the capability of dynamic contrast enhanced MR-mammography (MRM) for the interpretation of axillary lymph nodes (LNs) in patients with breast cancer. MATERIAL AND METHODS: 25 patients with breast cancer preoperatively underwent both FDG positron emission computed tomography (PET-CT) and dynamic contrast enhanced MRM. The maximum signal increase (SImax) and curve shape (types I-III) of contrast enhanced LNs ≥ 0.5 cm (short-axis) were analyzed in MRM and correlated to the maximum standard uptake value (SUVmax) of FDG PET-CT. 29 healthy women with MRM served as control group. Enhancement kinetics of all malignant LNs were compared to LN findings of the healthy control group. RESULTS: Overall 33 contrast enhanced LNs on preoperative MRM had a corresponding FDG uptake on PET-CT. 30 of the PET positive LNs were classified as surely malignant (mean SUVmax 7.3 (± 5.4)). The mean SImax of these LNs was not significantly different to the control group (222% vs 197%), but malignant LNs had a significantly higher rate of type III curves with rapid washout (93% vs 66%, p = 0.008). CONCLUSION: The maximum signal increase is not capable of differentiating malignant from benign axillary LNs. However, since malignant LNs showed a higher frequency of rapid washout curves (type III curves) on corresponding MRM future studies should concentrate on the analysis of this parameter. In clinical routine the curve shape still should be taken with care as there is a high overlap with benign LNs.

Performance evaluation of a new fourth-generation HIV combination antigen-antibody assay.

Education and diagnostic tests capable of early detection represent our most effective means of preventing transmission of human immunodeficiency virus (HIV). The importance of early detection is underlined by studies demonstrating increased life expectancy following early initiation of antiviral treatment. The Elecsys(®) HIV combi PT assay is a fourth-generation antigen-antibody combination assay developed to allow earlier detection of seroconversion, and to have increased sensitivity and improved specificity. We aimed to determine how early the assay could detect infection compared with existing assays; whether all HIV variants could be detected; and the assay's specificity using samples from blood donors, routine specimens, and patients with potential cross-reacting factors. Samples were identified as positive by the Elecsys(®) assay 4.9 days after a positive polymerase chain reaction result (as determined by the panel supplier), which was earlier than the 5.3-7.1 days observed with comparators. The analytical sensitivity of the Elecsys(®) HIV combi PT assay for the HIV-1 p24 antigen was 1.05 IU/mL, which compares favorably with the comparator assays. In addition, the Elecsys(®) assay identified all screened HIV subtypes and displayed greater sensitivity to HIV-2 homologous antigen and antibodies to HIV-1 E and O and HIV-2 than the other assays. Overall, the specificity of the Elecsys(®) assay was 99.88 % using samples from blood donors and 99.81 % when analyzing unselected samples. Potential cross-reacting factors did not interfere with assay performance. The Elecsys(®) HIV combi PT assay is a sensitive and specific assay that has been granted the CE mark according to Directive 2009/886/EC.