Using case specific experiments to evaluate fingermarks on knives given activity level propositions.

Bayesian networks have shown to be a useful tool for the evaluation of forensic findings given activity level propositions. In this paper, we demonstrate how case specific experiments can be used to assign probabilities to the states of the nodes of a Bayesian network for the evaluation of fingermarks given activity level propositions. The transfer, persistence and recovery of fingermarks on knives is studied in experiments where a knife is either used to stab a victim or to cut food, representing the activities that were disputed in the case of the murder of Meredith Kercher.

A study into evaluating the location of fingermarks on letters given activity level propositions.

A previous paper published in this journal proposed a model for evaluating the location of fingermarks on two-dimensional items (de Ronde, van Aken, de Puit and de Poot (2019)). In this paper, we apply the proposed model to a dataset consisting of letters to test whether the activity of writing a letter can be distinguished from the alternative activity of reading a letter based on the location of the fingermarks on the letters. An experiment was conducted in which participants were asked to read a letter and write a letter as separate activities on A4- and A5-sized papers.

The evaluation of fingermarks given activity level propositions.

Fingermarks are highly relevant in criminal investigations for individualization purposes. In some cases, the question in court changes from 'Who is the source of the fingermarks?' to 'How did the fingermark end up on the surface?'. In this paper, we explore the evaluation of fingermarks given activity level propositions by using Bayesian networks.

A study into fingermarks at activity level on pillowcases.

In this paper, we describe a promising method to evaluate the location of fingermarks on two-dimensional objects, which provides valuable information for the evaluation of fingermarks at activity level. For this purpose, an experiment with pillowcases was conducted at the Dutch music festival Lowlands, to test whether the activity 'smothering' can be distinguished from an alternative activity like 'changing a pillowcase' based on the touch traces on pillowcases left by the activities. Participants performed two activities with paint on their hands: smothering a victim with the use of a pillow and changing a pillowcase of a pillow.

A Novel Virus Causes Scale Drop Disease in Lates calcarifer.

From 1992 onwards, outbreaks of a previously unknown illness have been reported in Asian seabass (Lates calcarifer) kept in maricultures in Southeast Asia. The most striking symptom of this emerging disease is the loss of scales. It was referred to as scale drop syndrome, but the etiology remained enigmatic.

HIV-1 autologous antibody neutralization associates with mother to child transmission.

The HIV-1 characteristics associated with mother to child transmission (MTCT) are still poorly understood and if known would indicate where intervention strategies should be targeted. In contrast to horizontally infected individuals, exposed infants possess inherited antibodies (Abs) from their mother with the potential to protect against infection. We investigated the HIV-1 gp160 envelope proteins from seven transmitting mothers (TM) whose children were infected either during gestation or soon after delivery and from four non-transmitting mothers (NTM) with similar viral loads and CD4 counts.

HIV type 1 mother-to-child transmission facilitated by distinctive glycosylation sites in the gp120 envelope glycoprotein.

The human immunodeficiency virus type 1 (HIV-1) characteristics associated with mother-to-child transmission (MTCT) are still poorly understood. We studied a cohort of 30 mothers from Rwanda infected with HIV-1 subtype A or C viruses of whom seven infected their children either during gestation or soon after birth. CD4 counts and viral load did not significantly differ between nontransmitting mother (NTM) versus transmitting mother (TM) groups.

Mitochondrial DNA decline in T cells of HIV-1 seroconverters may be dependent on immune activation.

Background: Earlier reports have indicated that human immunodeficiency virus type 1 (HIV-1) infection itself might cause mitochondrial DNA (mtDNA) decline in peripheral blood mononuclear cells (PBMCs). However, the mtDNA dynamics within this heterogeneous cell population during HIV-1 infection are not fully understood.

Methods: mtDNA content was assessed longitudinally in PBMCs and in isolated CD4(+) and CD8(+) T cells from 16 documented HIV-1 seroconverters who were naive to antiretroviral therapy.

Adaptation of HIV-1 depends on the host-cell environment.

Many viruses have the ability to rapidly develop resistance against antiviral drugs and escape from the host immune system. To which extent the host environment affects this adaptive potential of viruses is largely unknown. Here we show that for HIV-1, the host-cell environment is key to the adaptive potential of the virus.

Identification of alternative amino acid substitutions in drug-resistant variants of the HIV-1 reverse transcriptase.

Objective/design: To identify new drug-resistance-associated mutations in the HIV-1 reverse transcriptase (RT) protein, we screened the RT sequence database of our hospital for alternative amino acid substitutions at known RT drug-resistance positions.

Method: The genotypic database used for this analysis contained 1322 RT sequences from 1015 patients. We analysed this RT database with a focus on alternative mutations at RT positions known to be involved in drug resistance.

Evolution of transmitted HIV-1 with drug-resistance mutations in the absence of therapy: effects on CD4+ T-cell count and HIV-1 RNA load.

Sequence analysis of HIV-1 from 440 therapy-naive individuals included within the CASCADE study, who seroconverted within 18 months of the last negative test, identified 65 persons infected with a strain carrying resistance-associated mutations. Population-based sequencing was performed for 20 of these individuals during the therapy-free follow-up period. The median time of follow-up was 15 months (interquartile range from 10 to 23 months).

Real-time nucleic acid sequence-based amplification assay to quantify changes in mitochondrial DNA concentrations in cell cultures and blood cells from HIV-infected patients receiving antiviral therapy.

Background: To study the clinical relevance of changes in mitochondrial DNA (mtDNA) in peripheral blood mononuclear cells (PBMCs) attributable to HIV infection and/or combination antiretroviral therapy (cART), a high-throughput molecular assay to quantify mtDNA is required.

Methods: We developed a quantitative real-time duplex nucleic acid sequence-based amplification assay in which both mtDNA and nuclear DNA are simultaneously amplified in 1 tube. The assay could accurately quantify mtDNA in a range of 15-1500 copies of mtDNA per 2 genomic copies with an intrarun variation of 11% and an interrun variation of 16%.

Infection with HIV-1 induces a decrease in mtDNA.

Cross-sectional studies have suggested that infection with human immunodeficiency virus (HIV) type 1 could reduce the mitochondrial DNA (mtDNA) content of blood cells. We investigated mtDNA content in peripheral blood mononuclear cells (PBMCs) obtained from 36 antiretroviral therapy-naive documented HIV-1 seroconverters, before and after seroconversion. mtDNA content statistically significantly decreased 1 year after seroconversion and showed a nonsignificant decrease during the subsequent 4 years.

Aggressive HIV-1?

New York City health officials announced on February 11, 2005 that a patient rapidly developed full-blown AIDS shortly after being diagnosed with a rare, drug-resistant strain of HIV-1. The New York City Department of Health issued an alert to all hospitals and doctors and a press conference was held to announce the emergence of an aggressive HIV-1 strain that may be difficult to treat and that appears to trigger rapid progression to AIDS. Is the panic justified?

Increased multinucleoside drug resistance and decreased replicative capacity of a human immunodeficiency virus type 1 variant with an 8-amino-Acid insert in the reverse transcriptase.

Resistance to antiretroviral drugs is generally conferred by specific amino acid substitutions, rather than insertions or deletions, in reverse transcriptase (RT) of human immunodeficiency virus type 1 (HIV-1). The exception to these findings is the amino acid insertions found in the beta3-beta4 loop of the RT enzyme in response to treatment with nucleoside reverse transcriptase inhibitors. This insert consists most commonly of two amino acids, but we describe in detail the evolution of a variant with an 8-amino-acid (aa) insert in a patient treated with zidovudine (ZDV) and 2'-3'-dideoxycytidine (ddC).

Prevalence of lipoatrophy and mitochondrial DNA content of blood and subcutaneous fat in HIV-1-infected patients randomly allocated to zidovudine- or stavudine-based therapy.

Introduction: Mitochondrial toxicity resulting from mitochondrial DNA (mtDNA) depletion is suggested to be involved in the pathogenesis of lipodystrophy.

Methods: We cross-sectionally assessed lipodystrophy both clinically and radiographically in patients who, 4 years before, had been enrolled in a randomized comparative trial of stavudine- or zidovudine-based therapy. mtDNA content was measured in peripheral blood mononuclear cells (PBMCs) and subcutaneous adipose tissue from the thigh and back.

Changes in mitochondrial DNA copy number in blood cells from HIV-infected patients undergoing antiretroviral therapy.

Mitochondrial DNA (mtDNA) copy number was measured in peripheral blood mononuclear cells (PBMCs) from 69 individuals using a real-time NASBA quantitative assay. Patients with HIV infection harbored significantly lower mtDNA copy number in PBMC than HIV-negative controls. Besides, subjects on stavudine-containing regimens showed significantly lower median mtDNA amounts than HIV-positive patients receiving other antiretroviral drugs, and this was associated with higher lactate levels.

Greater and more rapid depletion of mitochondrial DNA in blood of patients treated with dual (zidovudine+didanosine or zidovudine+zalcitabine) vs. single (zidovudine) nucleoside reverse transcriptase inhibitors.

Background: Most toxicities associated with nucleoside analogue reverse transcriptase inhibitors (NRTIs) are thought to result from mitochondrial toxicity. These toxicities include peripheral neuropathy, pancreatitis, lactic acidosis, and peripheral lipoatrophy. Unfortunately, there are no validated laboratory markers for clinically assessing, let alone predicting, the onset of mitochondrial toxicity associated with NRTI therapy.

Assessment of precision and concordance of quantitative mitochondrial DNA assays: a collaborative international quality assurance study.

Background: A number of international research groups have developed DNA quantitation assays in order to investigate the role of mitochondrial DNA depletion in anti-retroviral therapy-induced toxicities.

Objectives: A collaborative study was undertaken to evaluate intra-assay precision and between laboratory concordance of measurements of mitochondrial DNA quantity, as a component of a comprehensive quality assurance project.

Study Design: Four laboratories were asked to measure and report mitochondrial DNA and nuclear DNA genome copy number, as well as mitochondrial DNA copy number/cell, for 17 coded aliquots of DNA derived from serial dilutions of pooled DNA from a lymphoblastoid cell line.

Efficient human immunodeficiency virus replication requires a fine-tuned level of transcription.

Transcription represents a crucial step in the life cycle of human immunodeficiency virus (HIV) and is highly regulated. Here we show that the strength of the viral long terminal repeat (LTR) promoter is optimized for efficient replication. Artificially increasing the rate of LTR-driven transcription was strongly detrimental for viral fitness, and HIV was able to regain replication capacity by selecting for variants with a weaker LTR.

Carrier rate of zidovudine-resistant HIV-1: the impact of failing therapy on transmission of resistant strains.

Objective: Because maintenance of treatment success in HIV-1 infection requires viruses to remain therapy sensitive in drug-naive seropositive persons, we looked at the primary infections caused by drug-resistant HIV-1 over time. Furthermore, to study the coverage rate of therapy and therapy failure in relation to the transmission of resistant viruses a mathematical model was developed.

Design: The reverse transcriptase and protease genes of viruses were analysed in newly infected people in the period 1990-1998 in the Amsterdam Cohort Study on HIV infection and AIDS in homosexual men.

Potent antiretroviral therapy initiates normalization of hypergammaglobulinemia and a decline in HIV type 1-specific antibody responses.

Next to a profound T cell immunodeficiency, HIV-1 infection induces activation and dysfunction of B cells, resulting in hypergammaglobulinemia. Whereas T cell immune reconstitution with potent antiretroviral therapy has been extensively documented, limited data are available on B cell immune reconstitution. We studied the effect of potent antiretroviral therapy on antibody titers to the viral proteins gp120 and p24 and on total IgG concentrations.

Single rapid real-time monitored isothermal RNA amplification assay for quantification of human immunodeficiency virus type 1 isolates from groups M, N, and O.

Because human immunodeficiency virus type 1 (HIV-1) subtypes and circulating recombinant forms (CRFs) are spreading rapidly worldwide and are becoming less confined to a geographical area, RNA assays that can detect and quantify all HIV-1 isolates reliably are in demand. We have developed a fast, real-time monitored RNA assay based on an isothermal nucleic acid sequence-based amplification technology that amplifies a part of the long terminal repeat region of the HIV-1 genome. Real-time detection was possible due to the addition of molecular beacons to the amplification reaction that was monitored in a fluorimeter with a thermostat.

Establishment of new transmissible and drug-sensitive human immunodeficiency virus type 1 wild types due to transmission of nucleoside analogue-resistant virus.

Sequence analysis of human immunodeficiency virus type 1 (HIV-1) from 74 persons with acute infections identified eight strains with mutations in the reverse transcriptase (RT) gene at positions 41, 67, 68, 70, 215, and 219 associated with resistance to the nucleoside analogue zidovudine (AZT). Follow-up of the fate of these resistant HIV-1 strains in four newly infected individuals revealed that they were readily replaced by sensitive strains. The RT of the resistant viruses changed at amino acid 215 from tyrosine (Y) to aspartic acid (D) or serine (S), with asparagine (N) as a transient intermediate, indicating the establishment of new wild types.