Structure and chronology of a star dune at Erg Chebbi, Morocco, reveals why star dunes are rarely recognised in the rock record.

Star dunes are the tallest dunes on Earth and are amongst the larger and more spectacular aeolian landforms. Although they are widespread in modern sandy deserts, star dunes are rarely recognised in the rock record probably due to a lack of suitable sedimentary models. This paper presents a new sedimentary model for the structure of a star dune at Erg Chebbi in Morocco (Sahara Desert) on the basis of ground-penetrating radar (GPR) surveys. Individual sedimentary structures in star dunes are similar to those in linear or barchanoid dunes, likely leading to misidentification in the rock record. However, the suite of features described in this paper will permit identification of star dunes in future studies of the rock record. Optically stimulated luminescence (OSL) dating shows that accumulation of the Erg Chebbi star dune post-dates the end of the African Humid Period (AHP). At the base of the dune, there is an ~ 8000-year hiatus in the record. Since then, the dune has grown rapidly to create a 100 m high dune within the past 1000 years and is migrating towards the west. Changes in the cross-strata support the idea that star dune construction was accompanied by a change in the wind directions.

Oral and vaginal HIV pre-exposure prophylaxis product attribute preferences among female sex workers in the Mexico-US border region.

To assess the potential uptake of HIV pre-exposure prophylaxis (PrEP) products among female sex workers (FSWs) vulnerable to HIV infection, we examined the influence of product attributes on willingness to use products among 271 HIV-negative FSWs in Tijuana and Ciudad Juarez, Mexico (2016-2017). Via five-point Likert scale ratings, participants indicated their willingness to use hypothetical products with six attributes: formulation (pill, gel, liquid, or ring), frequency of use (daily, on-demand, or monthly), cost per use (10 or 200 pesos), effectiveness (40% or 80%), side effects (none or mild), and access point (healthcare clinic or non-governmental organization). Conjoint analysis was used to determine the impact of attributes on product ratings and identify preferred product attributes. Multinomial logistic regression was used to identify factors associated with formulation preferences. In both cities, formulation and frequency of use had the greatest impact on ratings. Participants in Ciudad Juarez indicated a strong preference for oral pills, whereas participants in Tijuana indicated roughly equal preferences for oral pills and vaginal gels. Monthly product use was preferred in both cities. Compared to preferring oral pills (38%), preferring vaginal gels (28%) was associated with practicing vaginal lubrication (adjusted odds ratio = 2.08; 95% confidence interval: 1.07-4.04). Oral PrEP may be acceptable to many FSWs in Tijuana and Ciudad Juarez; however, continued development of behaviorally-congruent vaginal PrEP products may also facilitate uptake and ensure sufficient coverage.

Laboratory Evaluation of a Point-of-Care Downward-Flow Assay for Simultaneous Detection of Antibodies to Treponema pallidum and Human Immunodeficiency Virus.

Combining the detection of syphilis and HIV antibodies into one point-of-care test integrates syphilis screening into already existing HIV screening programs, which may be particularly beneficial in settings such as antenatal care. Using the INSTI Multiplex downward-flow immunoassay, we tested 200 stored serum samples from high-risk patients enrolled in a longitudinal study on HIV infection and syphilis in Peruvian men who have sex with men and transgender women. This rapid assay detected HIV and Treponema pallidum serum antibodies with sensitivities of 100% (95% confidence interval [CI], 95.9% to 100%) and 87.4% (95% CI, 81.4% to 92.0%), respectively, and specificities of 95.5% (95% CI, 89.9% to 98.5%) and 97.0% (95% CI, 84.2% to 99.9%), respectively (n = 200). The sensitivity for syphilis antibody detection was higher in patients with a rapid plasma reagin titer of ≥1:8 (97.3%) than in those with a titer of ≤1:4 (90%) or a nonreactive titer (66.7%).

The other side of surveillance: Monitoring, application, and integration of tuberculosis data to guide and evaluate programme activities in South Africa.

BACKGROUND: The importance of using surveillance data to monitor and evaluate programme activities has been emphasised in international policies for tuberculosis (TB) control. OBJECTIVES: A survey was conducted to assess the use of TB surveillance data to monitor and guide TB programme activities in South Africa (SA). METHODS: As part of an evaluation of the SA national TB surveillance system, semi-structured interviews were conducted among TB staff at health facilities and offices in three provinces. At each site, all persons involved with TB care, management and surveillance were invited to participate. RESULTS: At least one person (range 1 - 4) was interviewed at 47/54 health facilities (87.0%), 11/13 subdistrict and district TB offices (84.6%), 2/3 provincial TB offices (66.7%), and at the national level (1/1, 100.0%). Of 119 TB staff, 64.7% recognised the purpose of TB surveillance as guiding programme planning, implementation and evaluation. However, only 16.0% reported using data to measure disease burden, 8.4% to monitor trends, and 9.2% to inform resource allocation. The majority reported using TB management tools provided by the national programme, but 44.5% also described using additional tools. Personnel mentioned the need for dedicated surveillance staff, training on recording and reporting, improved computer access, and methods to apply information from surveillance data to the programme. CONCLUSIONS: The majority of TB staff understood the purpose of surveillance but did not routinely use data to guide programme planning, implementation and evaluation. Training and supporting TB staff to utilise surveillance data will help improve the TB surveillance system.

Validation of sputum smear results in the Electronic TB Register for the management of tuberculosis, South Africa.

BACKGROUND: The accuracy of tuberculosis (TB) surveillance systems is paramount in TB control. In South Africa, information from the laboratory is not directly linked to the Electronic TB Register (ETR). OBJECTIVE: To validate smear results recorded in the ETR with those recorded in the laboratory. METHODS: A retrospective evaluation was conducted among all sputum smear-positive TB patients recorded in the ETR during the fourth quarter of 2009 in KwaZulu-Natal Province. RESULTS: Of 1036 smear-positive patients recorded in the ETR, 683 (65.9%) had positive results recorded in the laboratory register. Only 364 (53.2%) had their smear results recorded in the ETR at the end of the intensive phase of treatment; of 326 (89.6%) recorded as converted to smear-negative, 224 (61.5%) were confirmed as smear-negative in the laboratory. Of 331 patients with end-of-treatment results in the ETR, 302 (91.2%) were recorded as cured, but only 105 (34.8%) were confirmed in the laboratory. CONCLUSIONS: Over a third of TB patients registered as smear-positive in the ETR could not be confirmed based on laboratory results. Many patients did not have a laboratory record, lending to uncertainty as to the validity of the smear results and treatment outcomes recorded in the ETR.

Scale-up of isoniazid preventive therapy in PEPFAR-assisted clinical sites in South Africa.

We reviewed the implementation of isoniazid preventive therapy (IPT) in South Africa from January 2010 to March 2011. The South African National Department of Health distributed revised IPT guidelines in May 2010 to increase IPT use in eligible human immunodeficiency virus (HIV) infected patients. We found a dramatic increase in the absolute numbers of patients reported to have been initiated on IPT (from 3309 in January-March 2010 to 49 130 in January-March 2011), representing an increase in the proportion (1.0-10.5%) of potentially eligible HIV-infected patients started on IPT.

Description and evaluation of a serious game intervention to engage low secure service users with serious mental illness in the design and refurbishment of their environment.

Service user involvement in all levels of healthcare provision is the expectation of UK government policy. Involvement should not only include participation in the planning and delivery of health care but also the exercise of choice and opinions about that care. In practice, however, service user engagement is most often tokenistic, involving post hoc consultation over plans already committed to by services. This paper explores an Occupational Therapy-led initiative to use the Serious Game format to engage low secure service users with serious mental illness in the design, layout and refurbishment of their unit. Among other things how medication was to be dispensed on the new unit was explored by this game and led to significant replanning in response to service user involvement. The game format was found to be a useful tool in facilitating communication between professionals and a traditionally marginalized and powerless client group. It enabled service users to have a voice, it provided a format for that voice to be heard and made possible service-led change in the planning process.

Systems-level questions in Drosophila oogenesis.

This paper describes computational and experimental work on pattern formation in Drosophila egg development (oogenesis), an established experimental model for studying cell fate diversification in developing tissues. Epidermal growth factor receptor (EGFR) is a key regulator of pattern formation and morphogenesis in Drosophila oogenesis. EGFR signalling in oogenesis can be genetically manipulated and monitored at many levels, leading to large sets of heterogeneous data that enable the formulation of increasingly quantitative models of pattern formation in these systems.

Slow human immunodeficiency virus (HIV) infectivity correlated with low HIV coreceptor levels.

The absolute number of CD4+ lymphocytes in blood is prognostic for disease progression, yet the cell surface density of CD4 receptors or chemokine receptors on a single cell has not previously been found to be predictive of human immunodeficiency virus (HIV) infectivity outcome. It has recently been shown that human leukocyte elastase (HLE) and its ligand alpha(1) proteinase inhibitor (alpha(1)PI; alpha(1)antitrypsin) act as HIV fusion cofactors. The present study shows that decreased HIV infectivity is significantly correlated with decreased cell surface density of HLE but not with decreased CD4 nor chemokine receptors. In vitro HIV infectivity outcome in this study was predicted by the surface density of HLE on mononuclear phagocytes but not on lymphocytes. The set point HLE surface density was in part determined by alpha(1)PI. Decreased circulating alpha(1)PI was correlated with increased cell surface HLE and with increased HIV infectivity. The correlation of HIV infectivity outcome with surface HLE and circulating alpha(1)PI supports the utility of these HIV cofactors in diagnostic analysis and therapeutic intervention.

Self antigen prognostic for human immunodeficiency virus disease progression.

We have recently found that an extracellular protein, alpha(1) proteinase inhibitor (alpha(1)PI; alpha(1) antitrypsin), is required for in vitro human immunodeficiency virus (HIV) infectivity outcome. We show here in a study of HIV-seropositive patients that decreased viral load is significantly correlated with decreased circulating alpha(1)PI. In the asymptomatic category of HIV disease, 100% of patients manifest deficient levels of active alpha(1)PI, a condition known to lead to degenerative lung diseases and a dramatically reduced life span. Further, HIV-associated alpha(1)PI deficiency is correlated with circulating anti-alpha(1)PI immunoglobulin G. These results suggest that preventing HIV-associated alpha(1)PI deficiency may provide a strategic target for preventing HIV-associated pathophysiology.

Specific activity of alpha1proteinase inhibitor and alpha2macroglobulin in human serum: application to insulin-dependent diabetes mellitus.

The shifting balance between proteinases and proteinase inhibitors in blood, a function of their relative affinities and concentrations, has long been hypothesized to influence immune competency. The identification of proteinase-activated receptor responses in cells of the mononuclear phagocyte system suggests a potential explanation. The major serum proteinase inhibitor, alpha1proteinase inhibitor (alpha1PI, alpha1-antitrypsin), has been reported to increase in concentration during inflammation. Quantitative determination of serum alpha1PI has traditionally been performed nephelometrically; however, antigenically quantitated levels may not be representative of functional capacity. It has previously been observed that alpha1PI in serum exhibits bimodal behavior as the result of various concentrations of proteinase inhibitors, specifically alpha2macroglobulin (alpha2M) and inter-alpha-trypsin inhibitor, which compete in binding to a panel of serine proteinases. Consequently, it has not previously been possible to assign a numerical value for the specific activity of these competing proteinase inhibitors in serum. By applying known constants representing the association of proteinase inhibitors with porcine pancreatic elastase (PPE), the theoretical relationship between the functional and antigenic values for alpha1PI and alpha2M has been empirically derived allowing, for the first time, the calculation of their specific activities in serum. As predicted, the serum concentration of alpha1PI was found to be highly correlated with residual uninhibited PPE catalytic activity in healthy individuals, but not in individuals exhibiting fragmented or complexed alpha1PI. Using these techniques, both the antigenic and functional levels of alpha1PI were determined in sera from subjects with insulin-dependent diabetes mellitus (IDDM) who had been clinically diagnosed as having either periodontal disease or gingival health. Determination of quantitative levels by antigen-capture suggests that the IDDM subjects with periodontitis manifest dramatically increased levels of fragmented serum alpha1PI compared with their orally healthy counterparts or normal controls. In contrast, functional analysis of serum alpha1PI revealed no differences between the three subject populations. The elevated levels of antigenically determined serum alpha1PI reflect the inflammatory status of periodontal disease. These results support the importance of and provide methodology for determining the functionally active levels of alpha1PI allowing reexamination of changes detected during the acute phase of inflammation, replacement therapy, and longitudinal studies in relevant disease processes including malignancy and diabetes.

Alpha 1-antitrypsin deficiency and pregnancy.

Alpha1-antitrypsin deficiency is an inherited pulmonary disorder which results from a deficiency of a major plasma protease inhibitor. The onset and severity of symptoms vary widely and depend on the genotype and whether the patient smokes cigarettes. Alpha1-antitrypsin in pregnancy has only been previously reported twice. Our patient had a functional serum alpha1-antitrypsin level which was 15% of normal but was clinically asymptomatic and she did not smoke. Her genotype revealed a non-ZZ pattern. Her obstetric history was complicated by preterm labor in each of her five ongoing pregnancies. Alpha1-antitrypsin deficiency is inherited via two codominant autosomal genes. Although there is great variability in severity of disease, seriously affected patients may have emphysema and hepatic abnormalities. Patients with non-ZZ genotypes or who are heterozygotes may have favorable pregnancy outcomes.

Inhibition of HIV-1 by modification of a host membrane protease.

While it is clear that CD4 is the receptor for the gp120 envelope protein of HIV-1, substantial evidence suggests that other host cell proteins are required for successful membrane fusion. Studies were initiated to examine the potential for a protein receptor which has an elastase-like character to participate in fusion of HIV-1 with permissive host cells. A synthetic elastase inhibitor was shown to significantly reduce HIV-1 infectivity when present during, but not after, the initial contact between virus and cells. A human T cell elastase-like membrane component was purified and shown to be lipid-associated. By competitive inhibition, the purified protein was shown to bind gp160 within the HIV-1 fusion domain. The binding parameters of whole T cell membrane extract, with a hydrophobic pentapeptide representative of the fusion domain, suggested an elastase-like protein is the single, secondary T cell receptor for HIV-1 (K = 1 x 10(3) M-1). The pentapeptide interacted with porcine and human (epithelial and polymorphonuclear leukocyte), but not murine, elastase isoforms, suggesting its participation in the permissiveness of host cells to infection.

Nucleotide sequence of a 55 kbp region from the right end of the genome of a pathogenic African swine fever virus isolate (Malawi LIL20/1).

The nucleotide sequence of a 55098 bp region from the right end of the genome of a virulent African swine fever virus (ASFV) isolate (Malawi LIL20/1) has been determined. Translation of the sequence identified 67 major open reading frames (ORFs) which are closely spaced and read from both DNA strands. At six positions intergenic tandem repeat arrays are found. Comparison of the predicted amino acid sequences of encoded proteins with protein sequence databases identified a number of homologies. These include three subunits of RNA polymerase, a protein with homology to transcription factor SII (TFSII), a DNA ligase, two subunits of mRNA capping enzyme, a DNA topoisomerase type II, a dUTPase, a protein kinase, three helicases, a ubiquitin-conjugating enzyme, a protein with homology to the nif S and nif S-like proteins identified in some bacteria and Saccharomyces cerevisiae, a protein with homology to both a myeloid differentiation primary response antigen (MyD116) and to a herpes simplex virus-encoded neurovirulence-associated protein (ICP34.5), a protein with homology to the ASFV-encoded structural protein p22, two proteins with homology to copies of the ASFV-encoded multigene family 360 and one protein with homology to the ASFV-encoded multigene family 110. Four genes encode proteins which have homology to each other and constitute a new multigene family (MGF100). Nine ORFs encode proteins which contain predicted transmembrane domains. The possible functions of these predicted ASFV-encoded proteins are discussed and the evolutionary relationship of ASFV to other viruses are considered. Despite the similarities in genome structure and replication strategy of ASFV with poxviruses, sequence similarity between them is low and the organization of ASFV-encoded genes is not colinear with that of the orthopoxviruses.

Duplicated genes within the variable right end of the genome of a pathogenic isolate of African swine fever virus.

The right variable region of the genome of a pathogenic strain of African swine fever virus (ASFV), Malawi LIL20/1, has been sequenced and 15 open reading frames (ORFs) identified by computer analysis. Eight of these ORFs were found to be similar to previously described ASFV ORFs and three of these belong to two previously described multiple gene families (MGF), 360 and 110. Four of the remaining five ORFs belong to a novel MGF, designated MGF 100, and the last ORF encodes a protein that is similar to the virus structural protein, p22. Copies of MGF 110 and the gene coding for p22 have previously been characterized only at the left end of the ASFV genome. The organization of these genes suggests evolution by duplications, deletions and sequence transposition from one end of the genome to the other. Sequence comparisons of members of MGF 360 suggest that the Malawi LIL20/1 genome has undergone separate DNA rearrangements compared to the Ba71V genome. Lastly, one ORF was found to be similar to the myeloid differentiation primary response protein, MyD116 and to the herpes simplex virus neurovirulence-associated factor ICP34.5.

T cell antigen receptor immune complexes demonstrating biologic and proteolytic activity.

An elastase-like protease, recently recognized as a specific product of murine T cells, may functionally associate with the classical TCR. T cell elastase, found in combination with the natural elastase inhibitor alpha 1-antitrypsin (alpha 1-protease inhibitor, alpha 1-PI), is produced by both CD4+ and CD8+ T lymphocytes. T cell elastase and alpha 1-PI are found chemically associated with the TCR in an antigen-specific complex reminiscent of the Ig-complement 'immune complexes'.

African swine fever virus genome content and variability.

A 55 kilobase pair (kb) region from the right end of the virulent African swine fever virus isolate, Malawi LIL20/1, has been sequenced. The 68 major open reading frames (ORFs) encoded are generally closely spaced and read from both DNA strands across the complete sequence. Comparison of the amino acid sequences of predicted ORFs with sequence databases identified 15 ORFs which encode proteins that are similar to proteins of known function. Two ORFs are homologous to copies of multigene family 360 (MGF360) and one ORF is homologous to copies of multigene family 110 (MGF110). Both of these multigene families have been described previously.