Simple Estimation of Incident HIV Infection Rates in Notification Cohorts Based on Window Periods of Algorithms for Evaluation of Line-Immunoassay Result Patterns

Background Tests for recent infections (TRIs) are important for HIV surveillance. We have shown that a patient's antibody pattern in a confirmatory line immunoassay (Inno-Lia) also yields information on time since infection. We have published algorithms which, with a certain sensitivity and specificity, distinguish between incident (< = 12 months) and older infection. In order to use these algorithms like other TRIs, i.e., based on their windows, we now determined their window periods. Methods We classified Inno-Lia results of 527 treatment-naïve patients with HIV-1 infection < = 12 months according to incidence by 25 algorithms. The time after which all infections were ruled older, i.e. the algorithm's window, was determined by linear regression of the proportion ruled incident in dependence of time since infection. Window-based incident infection rates (IIR) were determined utilizing the relationship ‘Prevalence = Incidence x Duration’ in four annual cohorts of HIV-1 notifications. Results were compared to performance-based IIR also derived from Inno-Lia results, but utilizing the relationship ‘incident = true incident + false incident’ and also to the IIR derived from the BED incidence assay. Results Window periods varied between 45.8 and 130.1 days and correlated well with the algorithms' diagnostic sensitivity (R2 = 0.962; P<0.0001). Among the 25 algorithms, the mean window-based IIR among the 748 notifications of 2005/06 was 0.457 compared to 0.453 obtained for performance-based IIR with a model not correcting for selection bias. Evaluation of BED results using a window of 153 days yielded an IIR of 0.669. Window-based IIR and performance-based IIR increased by 22.4% and respectively 30.6% in 2008, while 2009 and 2010 showed a return to baseline for both methods. Conclusions IIR estimations by window- and performance-based evaluations of Inno-Lia algorithm results were similar and can be used together to assess IIR changes between annual HIV notification cohorts.

Socioemotional Wealth, Ambidexterity, and Family Firm Performance: An Empirical Study

While family business literature agrees that family firms are driven by both non-economic and financial motives, it is unclear how the prioritization of socioemotional wealth (SEW) over financial considerations affects family firms' financial performance. Based on a sample of 343 family firm owners from German-speaking Europe, this study reveals a significant and positive relationship between the firm owners' SEW considerations and their family businesses' financial performance. This relationship, in turn, is found to be mediated by organizational ambidexterity. A fine-grained analysis of the different SEW dimensions indicates that this pattern may be driven by two elements of socioemotional wealth only (family members' identification with the firm and emotional attachment). Our findings demonstrate that business families do not necessarily face a trade-off when prioritizing the preservation of their SEW over stabilizing or improving the financial performance of their business. The study enriches several streams of literature and opens up numerous avenues for future research.

Engaging Local Communities in Low Emissions Land-Use Planning: a Case Study from Laos

Reducing Emissions from Deforestation and Forest Degradation and enhancing forest carbon stocks (REDD+) is a performance-based payment mechanism currently being debated in international and national environmental policy and planning forums. As the mechanism is based on conditionality, payments must reflect land stewards’ level of compliance with carbon-efficient management practices. However, lack of clarity in land governance and carbon rights could undermine REDD+ implementation. Strategies are needed to avoid perverse incentives resulting from the commoditization of forest carbon stocks and, importantly, to identify and secure the rights of legitimate recipients of future REDD+ payments. We propose a landscape-level approach to address potential conflicts related to carbon tenure and REDD+ benefit sharing. We explore various land-tenure scenarios and their implications for carbon ownership in the context of a research site in northern Laos. Our case study shows that a combination of relevant scientific tools, knowledge, and participatory approaches can help avoid the marginalization of rural communities during the REDD+ process. The findings demonstrate that participatory land-use planning is an important step in ensuring that local communities are engaged in negotiating REDD+ schemes and that such negotiations are transparent. Local participation and agreements on land-use plans could provide a sound basis for developing efficient measurement, reporting, and verification systems for REDD+.

Numerical model of the human cornea based on stromal microstructure: identification of mechanical properties for two age groups

The optical quality of the human eye mainly depends on the refractive performance of the cornea. The shape of the cornea is a mechanical balance between intraocular pressure and tissue intrinsic stiffness. Several surgical procedures in ophthalmology alter the biomechanics of the cornea to provoke local or global curvature changes for vision correction. Legitimated by the large number of surgical interventions performed every day, the demand for a deeper understanding of corneal biomechanics is rising to improve the safety of procedures and medical devices. The aim of our work is to propose a numerical model of corneal biomechanics, based on the stromal microstructure. Our novel anisotropic constitutive material law features a probabilistic weighting approach to model collagen fiber distribution as observed on human cornea by Xray scattering analysis (Aghamohammadzadeh et. al., Structure, February 2004). Furthermore, collagen cross-linking was explicitly included in the strain energy function. Results showed that the proposed model is able to successfully reproduce both inflation and extensiometry experimental data (Elsheikh et. al., Curr Eye Res, 2007; Elsheikh et. al., Exp Eye Res, May 2008). In addition, the mechanical properties calculated for patients of different age groups (Group A: 65-79 years; Group B: 80-95 years) demonstrate an increased collagen cross-linking, and a decrease in collagen fiber elasticity from younger to older specimen. These findings correspond to what is known about maturing fibrous biological tissue. Since the presented model can handle different loading situations and includes the anisotropic distribution of collagen fibers, it has the potential to simulate clinical procedures involving nonsymmetrical tissue interventions. In the future, such mechanical model can be used to improve surgical planning and the design of next generation ophthalmic devices.

Light-emitting diode and laser fluorescence-based devices in detecting occlusal caries

The aim of this study was to assess the performance of two light-emitting diode (LED)- and two laser fluorescence-based devices in detecting occlusal caries in vitro. Ninety-seven permanent molars were assessed twice by two examiners using two LED- (Midwest Caries - MID and VistaProof - VP) and two laser fluorescence-based (DIAGNOdent 2095 - LF and DIAGNOdent pen 2190 - LFpen) devices. After measuring, the teeth were histologically prepared and classified according to lesion extension. At D1 the specificities were 0.76 (LF and LFpen), 0.94 (MID), and 0.70 (VP); the sensitivities were 0.70 (LF), 0.62 (LFpen), 0.31 (MID), and 0.75 (VP). At D(3) threshold the specificities were 0.88 (LF), 0.87 (LFpen), 0.90 (MID), and 0.70 (VP); the sensitivities were 0.63 (LF and LFpen), 0.70 (MID), and 0.96 (VP). Spearman's rank correlations with histology were 0.56 (LF), 0.51 (LFpen), 0.55 (MID), and 0.58 (VP). Inter- and intraexaminer ICC values were high and varied from 0.83 to 0.90. Both LF devices seemed to be useful auxiliary tools to the conventional methods, presenting good reproducibility and better accuracy at D(3) threshold. MID was not able to differentiate sound surfaces from enamel caries and VP still needs improvement on the cut-off limits for its use.

Comparison of the effect of a CIDR-Select synch versus a long-term CIDR based AI protocol on reproductive performance in multiparous dairy cows in Swiss dairy farms

Background Synchronization programs have become standard in the dairy industry in many countries. In Switzerland, these programs are not routinely used for groups of cows, but predominantly as a therapy for individual problem cows. The objective of this study was to compare the effect of a CIDR-Select Synch and a 12-d CIDR protocol on the pregnancy rate in healthy, multiparous dairy cows in Swiss dairy farms. Methods Cows (N = 508) were randomly assigned to CIDR-Select Synch (N = 262) or 12-d CIDR (N = 246) protocols. Cows in the CIDR-Select Synch group received a CIDR and 2.5 ml of buserelin i.m. on d 0. On d 7, the CIDR insert was removed and 5 ml of dinoprost was administered i.m.. Cows in the 12-d CIDR group received the CIDR on d 0 and it was removed on d 12 (the routine CIDR protocol in Swiss dairies). On d 0 a milk sample for progesterone analysis was taken. Cows were inseminated upon observed estrus. Pregnancy was determined at or more than 35 days after artificial insemination. As a first step, the two groups were compared as to indication for treatment, breed, stud book, stall, pasture, and farmer's business using chi square tests or Fisher's exact test. Furthermore, groups were compared as to age, DIM, number of AI's, number of cows per farm, and yearly milk yield per cow using nonparametric ANOVA. A multiple logistic model was used to relate the success of the protocols to all of the available factors; in particular treatment (CIDR-Select Synch/12-d CIDR), milk progesterone value, age, DIM, previous treatment of the uterus, previous gynecological treatment, and number of preceding inseminations. Results The pregnancy rate was higher in cows following the CIDR-Select Synch compared to the 12-d CIDR protocol (50.4% vs. 22.4%; P < 0.0001). Conclusion The CIDR-Select Synch protocol may be highly recommended for multiparous dairy cows. The reduced time span of the progesterone insert decreased the number of days open, improved the pregnancy rate compared to the 12-d CIDR protocol and the cows did not to have to be handled more often.

The performance of conventional and fluorescence-based methods for occlusal caries detection: an in vivo study with histologic validation

The authors conducted an in vivo study to determine clinical cutoffs for a laser fluorescence (LF) device, an LF pen and a fluorescence camera (FC), as well as to evaluate the clinical performance of these methods and conventional methods in detecting occlusal caries in permanent teeth by using the histologic gold standard for total validation of the sample.

Time-lapse microscopy and classification of 2D human mesenchymal stem cells based on cell shape picks up myogenic from osteogenic and adipogenic differentiation

Current methods to characterize mesenchymal stem cells (MSCs) are limited to CD marker expression, plastic adherence and their ability to differentiate into adipogenic, osteogenic and chondrogenic precursors. It seems evident that stem cells undergoing differentiation should differ in many aspects, such as morphology and possibly also behaviour; however, such a correlation has not yet been exploited for fate prediction of MSCs. Primary human MSCs from bone marrow were expanded and pelleted to form high-density cultures and were then randomly divided into four groups to differentiate into adipogenic, osteogenic chondrogenic and myogenic progenitor cells. The cells were expanded as heterogeneous and tracked with time-lapse microscopy to record cell shape, using phase-contrast microscopy. The cells were segmented using a custom-made image-processing pipeline. Seven morphological features were extracted for each of the segmented cells. Statistical analysis was performed on the seven-dimensional feature vectors, using a tree-like classification method. Differentiation of cells was monitored with key marker genes and histology. Cells in differentiation media were expressing the key genes for each of the three pathways after 21 days, i.e. adipogenic, osteogenic and chondrogenic, which was also confirmed by histological staining. Time-lapse microscopy data were obtained and contained new evidence that two cell shape features, eccentricity and filopodia (= 'fingers') are highly informative to classify myogenic differentiation from all others. However, no robust classifiers could be identified for the other cell differentiation paths. The results suggest that non-invasive automated time-lapse microscopy could potentially be used to predict the stem cell fate of hMSCs for clinical application, based on morphology for earlier time-points. The classification is challenged by cell density, proliferation and possible unknown donor-specific factors, which affect the performance of morphology-based approaches. Copyright © 2012 John Wiley & Sons, Ltd.

Diagnostic performance of line-immunoassay based algorithms for incident HIV-1 infection

Background Serologic testing algorithms for recent HIV seroconversion (STARHS) provide important information for HIV surveillance. We have previously demonstrated that a patient's antibody reaction pattern in a confirmatory line immunoassay (INNO-LIA™ HIV I/II Score) provides information on the duration of infection, which is unaffected by clinical, immunological and viral variables. In this report we have set out to determine the diagnostic performance of Inno-Lia algorithms for identifying incident infections in patients with known duration of infection and evaluated the algorithms in annual cohorts of HIV notifications. Methods Diagnostic sensitivity was determined in 527 treatment-naive patients infected for up to 12 months. Specificity was determined in 740 patients infected for longer than 12 months. Plasma was tested by Inno-Lia and classified as either incident (< = 12 m) or older infection by 26 different algorithms. Incident infection rates (IIR) were calculated based on diagnostic sensitivity and specificity of each algorithm and the rule that the total of incident results is the sum of true-incident and false-incident results, which can be calculated by means of the pre-determined sensitivity and specificity. Results The 10 best algorithms had a mean raw sensitivity of 59.4% and a mean specificity of 95.1%. Adjustment for overrepresentation of patients in the first quarter year of infection further reduced the sensitivity. In the preferred model, the mean adjusted sensitivity was 37.4%. Application of the 10 best algorithms to four annual cohorts of HIV-1 notifications totalling 2'595 patients yielded a mean IIR of 0.35 in 2005/6 (baseline) and of 0.45, 0.42 and 0.35 in 2008, 2009 and 2010, respectively. The increase between baseline and 2008 and the ensuing decreases were highly significant. Other adjustment models yielded different absolute IIR, although the relative changes between the cohorts were identical for all models. Conclusions The method can be used for comparing IIR in annual cohorts of HIV notifications. The use of several different algorithms in combination, each with its own sensitivity and specificity to detect incident infection, is advisable as this reduces the impact of individual imperfections stemming primarily from relatively low sensitivities and sampling bias.

Performance of a new, 3D-monitor based random-dot stereotest for children under 4 years of age

BACKGROUND: The aim of this study was to determine the performance of a new, 3D-monitor based, objective stereotest in children under the age of four. METHODS: Random-dot circles (diameter 10 cm, crossed, disparity of 0.34 degrees) randomly changing their position were presented on an 3D-monitor while eye movements were monitored by infrared photo-oculography. If > or = 3 consecutive stimuli were seen, a positive response was assumed. One hundred thirty-four normal children aged 2 months to 4 years (average 17+/-15.3 months) were examined. RESULTS: Below the age of 12 months, we were not able to obtain a response to the 3D stimulus. For older children the following rates of positive responses were found: 12-18 months 25%, 18-24 months 10%, 24-30 months 16%, 30-36 months 57%, 36-42 months 100%, and 42-48 months 91%. Multiple linear logistic regression showed a significant influence on stimulus recognition of the explanatory variables age (p<0.00001) and child cooperation (p<0.001), but not of gender (p>0.1). CONCLUSIONS: This 3D-monitor based stereotest allows an objective measurement of random-dot stereopsis in younger children. It might open new ways to screen children for visual abnormalities and to study the development of stereovision. However, the current experimental setting does not allow determining random-dot stereopsis in children younger than 12 months.