Substitutions due to antiretroviral toxicity or contraindication in the first 3 years of antiretroviral therapy in a large South African cohort

INTRODUCTION: The patterns and reasons for antiretroviral therapy (ART) drug substitutions are poorly described in resource-limited settings. METHODS: Time to and reason for drug substitution were recorded in treatment-naive adults receiving ART in two primary care treatment programmes in Cape Town. The cumulative proportion of patients having therapy changed because of toxicity was described for each drug, and associations with these changes were explored in multivariate models. RESULTS: Analysis included 2,679 individuals followed for a median of 11 months. Median CD4+ T-cell count at baseline was 85 cells/microl. Mean weight was 59 kg, mean age was 32 years and 71% were women. All started non-nucleoside reverse transcriptase inhibitor-based ART (60% on efavrienz) and 75% started on stavudine (d4T). After 3 years, 75% remained in care on-site, of whom 72% remained on their initial regimen. Substitutions due to toxicity of nevirapine (8% by 3 years), efavirenz (2%) and zidovudine (8%) occurred early. Substitutions on d4T occurred in 21% of patients by 3 years, due to symptomatic hyperlactataemia (5%), lipodystrophy (9%) or peripheral neuropathy (6%), and continued to accumulate over time. Those at greatest risk of hyperlactataemia or lipodystrophy were women on ART > or =6 months, weighing > or =75 kg at baseline. DISCUSSION: A high proportion of adult patients are able to tolerate their initial ART regimen for up to 3 years. In most instances treatment-limiting toxicities occur early, but continue to accumulate over time in patients on d4T. Whilst awaiting other treatment options, the risks of known toxicities could be minimized through early identification of patients at the highest risk.

Maxillary sinus grafting with Bio-Oss or Straumann Bone Ceramic: histomorphometric results from a randomized controlled multicenter clinical trial

INTRODUCTION: This investigation was designed to compare the histomorphometric results from sinus floor augmentation with anorganic bovine bone (ABB) and a new biphasic calcium phosphate, Straumann Bone Ceramic (BCP). MATERIALS AND METHODS: Forty-eight maxillary sinuses were treated in 37 patients. Residual bone width was > or =6 mm and height was > or =3 mm and <8 mm. Lateral sinus augmentation was used, with grafting using either ABB (control group; 23 sinuses) or BCP (test group; 25 sinuses); sites were randomly assigned to the control or test groups. After 180-240 days of healing, implant sites were created and biopsies taken for histological and histomorphometric analyses. The parameters assessed were (1) area fraction of new bone, soft tissue, and graft substitute material in the grafted region; (2) area fraction of bone and soft tissue components in the residual alveolar ridge compartment; and (3) the percentage of surface contact between the graft substitute material and new bone. RESULTS: Measurable biopsies were available from 56% of the test and 81.8% of the control sites. Histology showed close contact between new bone and graft particles for both groups, with no significant differences in the amount of mineralized bone (21.6+/-10.0% for BCP vs. 19.8+/-7.9% for ABB; P=0.53) in the biopsy treatment compartment of test and control site. The bone-to-graft contact was found to be significantly greater for ABB (48.2+/-12.9% vs. 34.0+/-14.0% for BCP). Significantly less remaining percentage of graft substitute material was found in the BCP group (26.6+/-5.2% vs. 37.7+/-8.5% for ABB; P=0.001), with more soft tissue components (46.4+/-7.7% vs. 40.4+/-7.3% for ABB; P=0.07). However, the amount of soft tissue components for both groups was found not to be greater than in the residual alveolar ridge. DISCUSSION: Both ABB and BCP produced similar amounts of newly formed bone, with similar histologic appearance, indicating that both materials are suitable for sinus augmentation for the placement of dental implants. The potential clinical relevance of more soft tissue components and different resorption characteristics of BCP requires further investigation.

Dissemination of methicillin-resistant Staphylococcus aureus USA300 sequence type 8 lineage in Latin America.

BACKGROUND: Methicillin-resistant Staphylococus aureus (MRSA) is an important nosocomial and community-associated (CA) pathogen. Recently, a variant of the MRSA USA300 clone emerged and disseminated in South America, causing important clinical problems. METHODS: S. aureus isolates were prospectively collected (2006-2008) from 32 tertiary hospitals in Colombia, Ecuador, Peru, and Venezuela. MRSA isolates were subjected to antimicrobial susceptibility testing and pulsed-field gel electrophoresis and were categorized as health care-associated (HA)-like or CA-like clones on the basis of genotypic characteristics and detection of genes encoding Panton-Valentine leukocidin and staphylococcal cassette chromosome (SCC) mec IV. In addition, multilocus sequence typing of representative isolates of each major CA-MRSA pulsotype was performed, and the presence of USA300-associated toxins and the arcA gene was investigated for all isolates categorized as CA-MRSA. RESULTS: A total of 1570 S. aureus were included; 651 were MRSA (41%)--with the highest rate of MRSA isolation in Peru (62%) and the lowest in Venezuela (26%)--and 71%, 27%, and 2% were classified as HA-like, CA-like, and non-CA/HA-like clones, respectively. Only 9 MRSA isolates were confirmed to have reduced susceptibility to glycopeptides (glycopeptide-intermediate S. aureus phenotype). The most common pulsotype (designated ComA) among the CA-like MRSA strains was found in 96% of isolates, with the majority (81%) having a < or =6-band difference with the USA300-0114 strain. Representative isolates of this clone were sequence type 8; however, unlike the USA300-0114 strain, they harbored a different SCCmec IV subtype and lacked arcA (an indicator of the arginine catabolic mobile element). CONCLUSION: A variant CA-MRSA USA300 clone has become established in South America and, in some countries, is endemic in hospital settings.

Cancer risk and use of protease inhibitor or nonnucleoside reverse transcriptase inhibitor-based combination antiretroviral therapy: the d: a: d study.

BACKGROUND The association between combination antiretroviral therapy (cART) and cancer risk, especially regimens containing protease inhibitors (PIs) or nonnucleoside reverse transcriptase inhibitors (NNRTIs), is unclear. METHODS Participants were followed from the latest of D:A:D study entry or January 1, 2004, until the earliest of a first cancer diagnosis, February 1, 2012, death, or 6 months after the last visit. Multivariable Poisson regression models assessed associations between cumulative (per year) use of either any cART or PI/NNRTI, and the incidence of any cancer, non-AIDS-defining cancers (NADC), AIDS-defining cancers (ADC), and the most frequently occurring ADC (Kaposi sarcoma, non-Hodgkin lymphoma) and NADC (lung, invasive anal, head/neck cancers, and Hodgkin lymphoma). RESULTS A total of 41,762 persons contributed 241,556 person-years (PY). A total of 1832 cancers were diagnosed [incidence rate: 0.76/100 PY (95% confidence interval: 0.72 to 0.79)], 718 ADC [0.30/100 PY (0.28-0.32)], and 1114 NADC [0.46/100 PY (0.43-0.49)]. Longer exposure to cART was associated with a lower ADC risk [adjusted rate ratio: 0.88/year (0.85-0.92)] but a higher NADC risk [1.02/year (1.00-1.03)]. Both PI and NNRTI use were associated with a lower ADC risk [PI: 0.96/year (0.92-1.00); NNRTI: 0.86/year (0.81-0.91)]. PI use was associated with a higher NADC risk [1.03/year (1.01-1.05)]. Although this was largely driven by an association with anal cancer [1.08/year (1.04-1.13)], the association remained after excluding anal cancers from the end point [1.02/year (1.01-1.04)]. No association was seen between NNRTI use and NADC [1.00/year (0.98-1.02)]. CONCLUSIONS Cumulative use of PIs may be associated with a higher risk of anal cancer and possibly other NADC. Further investigation of biological mechanisms is warranted.

PEDro or Cochrane to Assess the Quality of Clinical Trials? A Meta-Epidemiological Study.

OBJECTIVE There is debate on how the methodological quality of clinical trials should be assessed. We compared trials of physical therapy (PT) judged to be of adequate quality based on summary scores from the Physiotherapy Evidence Database (PEDro) scale with trials judged to be of adequate quality by Cochrane Risk of Bias criteria. DESIGN Meta-epidemiological study within Cochrane Database of Systematic Reviews. METHODS Meta-analyses of PT trials were identified in the Cochrane Database of Systematic Reviews. For each trial PeDro and Cochrane assessments were extracted from the PeDro and Cochrane databases. Adequate quality was defined as adequate generation of random sequence, concealment of allocation, and blinding of outcome assessors (Cochrane criteria) or as trials with a PEDro summary score ≥5 or ≥6 points. We combined trials of adequate quality using random-effects meta-analysis. RESULTS Forty-one Cochrane reviews and 353 PT trials were included. All meta-analyses included trials with PEDro scores ≥5, 37 (90.2%) included trials with PEDro scores ≥6 and only 22 (53.7%) meta-analyses included trials of adequate quality according to the Cochrane criteria. Agreement between PeDro and Cochrane was poor for PeDro scores of ≥5 points (kappa = 0.12; 95% CI 0.07 to 0.16) and slight for ≥6 points (kappa 0.24; 95% CI 0.16-0.32). When combining effect sizes of trials deemed to be of adequate quality according to PEDro or Cochrane criteria, we found that a substantial difference in the combined effect size (≥0.15) was evident in 9 (22%) out of the 41 meta-analyses for PEDro cutoff ≥5 and 10 (24%) for cutoff ≥6. CONCLUSIONS The PeDro and Cochrane approaches lead to different sets of trials of adequate quality, and different combined treatment estimates from meta-analyses of these trials. A consistent approach to assessing RoB in trials of physical therapy should be adopted.

Geochemical analyses of chert nodules and beds from deep-sea sediments (Table 1)

Concentrations of Fe, Mg, Ca, Sr, Mn, Zn, and other heavy metals were analyzed by atomic absorption spectrometry in 27 chert samples from the Pacific deep sea, 17 chert samples from land, and 4 associated sediments from the Pacific Ocean. Among the elements, Fe and Mg concentrations are highly correlatable as are the relationships between Ca and Sr, or between Ca and CO2. The correlation between Fe and Mg is particularly high for Pacific deep-sea flints and cherts, and for cherts of deep-sea origin from outcrops on land. Enrichments in heavy metals were recognized in some deep-sea cherts; volcanogenic cherts are enriched in Fe, a chert nodule containing basaltic fragments is enriched in Zn and Cr, and biogenically enclosed carbonates in flint nodules are enriched in Mn. The correlation of Fe and Mg and their constant ratio [Mg(%)/Fe(%)] of around 0.33 might be characteristic features in the pelagic clays contained in deep-sea flints and cherts, and the concentrations of heavy metals in them would be controlled by the concentrations of Fe-Mg correlated clays. Although the mineralogical nature of the Fe-Mg clay in deep-sea cherts was not clarified by dissolution experiments on opaline minerals in chert, the high concentrations of Fe-montmorillonite and fine-grained olivine or other ferromagnesian silicate minerals in the clay may result in the high correlations between Fe and Mg.

Calcareous nannofossil during the Paleocene Eocene Thermal Maximum in sediments of Walvish Ridge

Compositions and abundances of calcareous nannofossil taxa have been determined in a ca 170 kyrs long time interval across the Paleocene/Eocene boundary at 1-cm to 10-cm resolution from two ODP Sites (1262, 1263) drilled along the flank of the Walvis Ridge in the South Atlantic. The results are compared to published data from ODP Site 690 in the Weddell Sea. The assemblages underwent rapid evolution over a 74 kyrs period, indicating stressed, unstable and/or extreme photic zone environments during the PETM hyperthermal. This rapid evolution, which created 5 distinct stratigraphic horizons, is consistent with the restricted brief occurrences of malformed and/or weakly calcified morphotypes. The production of these aberrant morphotypes is possibly caused by major global scale changes in carbon cycling in the ocean-atmosphere system, affecting also photic zone environments. No marked paleoecologically induced changes are observed in abundances of the genera Discoaster, Fasciculithus and Sphenolithus at the Walvis Ridge sites. Surprisingly, there is no significant correlation in abundance between these three genera, presumed to have had a similar paleoecological preference for warm and oligotrophic conditions.

Middle Miocene stable carbon and oxygen isotope record of foraminifera of ODP Hole 120-747A

Paleoceanographic variability at southern high latitude Ocean Drilling Program (ODP) Site 747 was investigated in this study through the interval which spans the Middle Miocene Climate Transition (MMCT). Between 15.0 and 12.2 million years ago (Ma), foraminiferal d18O records derived from both benthic (Cibicidoides spp.) and planktonic taxa (Globorotalia praescitula and Globigerina bulloides) reveal a history of changes in water column thermal and salinity structure and a strong imprint of seasonality. Prior to the MMCT, in the interval between 14.35 and 13.9 Ma, G. bulloides displays relatively high d18O values similar to those of G. praescitula, interpreted to indicate weakening of the thermocline and/or increased seasonality with cooler early-spring and/or late-fall temperatures. Following this interval, G. bulloidesd18O values diverge significantly from benthic and G. praescitula values, with G. bulloides values remaining relatively low for at least 600 kyr following the benthic foraminiferal d18O shift during the MMCT at ~13.9 Ma. This divergence in d18O records occurs in direct association with the Mi3 cooling and glaciation event and may suggest: (1) a strengthening of the vertical temperature gradient, with greater cooling of deep waters than surface waters, (2) changes in the depth habitat of G. bulloides, (3) changes in the dominant season of G. bulloides calcification, (4) modification of surface-water d18O values in association with enhanced sea-ice formation, (5) increased surface-water carbonate ion concentration, and/or (6) a significant decrease in surface-water salinity across the MMCT. The first of these possible scenarios is not likely, particularly in light of recent Mg/Ca evidence for significant surface-water cooling in the Southern Ocean associated with the MMCT. Of the remaining possibilities, we favor a change in surface salinity to explain the observed trends in d18O values and hypothesize that surface salinity may have decreased by up to 2 salinity units at ~13.9 Ma. In this scenario, the development of a lower-salinity Antarctic surface layer coincided with regional cooling of both surface and deep waters of the Southern Ocean during the Mi3 glaciation of East Antarctica, and contributed into the dominance of Neogloboquadrina spp. between 13.8 and 13.2 Ma. Additionally, the distinct patterns observed in planktonic foraminiferal d18O records spanning the MMCT correspond with changes in the vertical d13C gradient between planktonic and benthic foraminiferal records and major changes in planktonic foraminiferal assemblages at Site 747, providing further evidence of the environmental significance of this climatic transition.

Chemical and Sr isotopic compositions of pore fluids and marine carbonates from ODP Hole 130-807A

The 87Sr/86Sr ratios and Sr concentrations in sediment and pore fluids are used to evaluate the rates of calcite recrystallization at ODP Site 807A on the Ontong Java Plateau, an 800-meter thick section of carbonate ooze and chalk. A numerical model is used to evaluate the pore fluid chemistry and Sr isotopes in an accumulating section. The deduced calcite recrystallization rate is 2% per million years (%/Myr) near the top of the section and decreases systematically in older parts of the section such that the rate is close to 0.1/age (in years). The deduced recrystallization rates have important implications for the interpretation of Ca and Mg concentration profiles in the pore fluids. The effect of calcite recrystallization on pore fluid chemistry is described by the reaction length, L, which varies by element, and depends on the concentration in pore fluid and solid. When L is small compared to the thickness of the sedimentary section, the pore fluid concentration is controlled by equilibrium or steady-state exchange with the solid phase, except within a distance L of the sediment-water interface. When L is large relative to the thickness of sediment, the pore fluid concentration is mostly controlled by the boundary conditions and diffusion. The values of L for Ca, Sr, and Mg are of order 15, 150, and 1500 meters, respectively. L_Sr is derived from isotopic data and modeling, and allows us to infer the values of L_Ca and L_Mg. The small value for L_Ca indicates that pore fluid Ca concentrations, which gradually increase down section, must be equilibrium values that are maintained by solution-precipitation exchange with calcite and do not reflect Ca sources within or below the sediment column. The pore fluid Ca measurements and measured alkalinity allow us to calculate the in situ pH in the pore fluids, which decreases from 7.6 near the sediment-water interface to 7.1+/-0.1 at 400-800 mbsf. While the calculated pH values are in agreement with some of the values measured during ODP Leg 130, most of the measurements are artifacts. The large value for L_Mg indicates that the pore fluid Mg concentrations at 807A are not controlled by calcite-fluid equilibrium but instead are determined by the changing Mg concentration of seawater during deposition, modified by aqueous diffusion in the pore fluids. We use the pore fluid Mg concentration profile at Site 807A to retrieve a global record for seawater Mg over the past 35 Myr, which shows that seawater Mg has increased rapidly over the past 10 Myr, rather than gradually over the past 60 Myr. This observation suggests that the Cenozoic rise in seawater Mg is controlled by continental weathering inputs rather than by exchange with oceanic crust. The relationship determined between reaction rate and age in silicates and carbonates is strikingly similar, which suggests that reaction affinity is not the primary determinant of silicate dissolution rates in nature.

Sediments in arctic sea ice - entrainment, characterization and quantification

Sediments in Arctic sea ice are important for erosion and redistribution and consequently a factor for the sediment budget of the Arctic Ocean. The processes leading to the incorporation of sediments into the ice are not understood in detail yet. In the present study, experiments on the incorporation of sediments were therefore conducted in ice tanks of The Hamburg Ship Model Basin (HSVA) in winter 1996/1997, These experiments showed that on average 75 % of the artificial sea-ice sediments were located in the brine-channel system. The sediments were scavenged from the water column by frazil ice. Sediments functioning as a nucleus for the formation of frazil ice were less important for the incorporation. Filtration in grease ice during relatively calm hydrodynamic conditions was probably an effective process to enrich sediments in the ice. Wave fields did not play an important role for the incorporation of sediments into the artificial sea ice. During the expedition TRANSDRIFT III (TDIII, October 1995), different types of natural, newly-formed sea ice (grease ice, nilas and young ice) were sampled in the inner Laptev Sea at the time of freeze-up. The incorporation of sediments took place during calm meteorological conditions then. The characteristics of the clay mineral assemblages of these sedirnents served as references for sea-ice sediments which were sampled from first-year drift ice in the outer Laptev Sea and the adjacent Arctic Ocean during the POLARSTERN expedition ARK-XI/1 (July-September 1995). Based on the clay mineral assemblages, probable incorporation areas for the sedirnents in first-year drift ice could be statistically reconstructed in the inner Laptev Sea (eastern, central, and Western Laptev Sea) as well as in adjacent regions. Comparing the amounts of particulate organic carbon (POC) in sea-ice sediments and in surface sediments from the shelves of potential incorporation areas often reveals higher values in sea-ice sediments (TDIII: 3.6 %DM; ARK-XI/1: 2.3 %DM). This enrichment of POC is probably due to the incorporation process into the sea ice, as could be deducted from maceral analysis and Rock-Eval pyrolysis. Both methods were applied in the present study to particulate organic material (POM) from sea-ice sediments for the first time. It was shown that the POM of the sea-ice sediments from the Laptev Sea and the adjacent Arctic Ocean was dominated by reworked, strongly fragmented, allochthonous (terrigenous) material. This terrigenous component accounted for more than 75 % of all counted macerals. The autochthonous (marine) component was also strongly fragmented, and higher in the sediments from newly-formed sea ice (24 % of all counted macerals) as compared to first-year drift ice (17 % of all counted macerals). Average hydroge indices confirmed this pattern and were in the transition zone between kerogen types II and III (TDIII: 275 mg KW/g POC; ARK-XI/1: 200 mg KW/g POC). The sediment loads quantified in natural sea ice (TDIII: 33.6 mg/l, ARK-XI/1: 49.0 mg/l) indicated that sea-ice sediments are an important factor for the sediment budget in the Laptev Sea. In particular during the incorporation phase in autumn and early winter, about 12 % of the sediment load imported annually by rivers into the Laptev Sea can be incorporated into sea ice and redistributed during calm meteorological conditions. Single entrainment events can incorporate about 35 % of the river input into the sea ice (ca. 9 x 10**6 t) and export it via the Transpolar Drift from the Eurasian shelf to the Fram Strait.

Sharḥ al-Nukhbah fī uṣūl ʻilm al-ḥadīth / lil-ʻAllāmah Ibn Ḥajar : manuscript, 1725 or 1726

Title from f. 1r.

The wonders of nature and art; or, A concise account of whatever is most curious and remarkable in the world; whether relating to its animal, vegetable and mineral productions, or to the manufactures, buildings and inventions of its inhabitants, compiled from historical and geographical works of established celebrity, and illustrated with the discoveries of modern travellers.

Mode of access: Internet.

Naẓm al-Jamīʻ al-ṣaghīr, [late 15th century?].

Fine copy of Abū Naṣr al-Farāḥī's (d.1242) versification of al-Jamīʻ al-ṣaghīr fī al-furūʻ, the well-known legal treatise by Muḥammad ibn al-Ḥasan al-Shaybānī (d.804). Excerpts from Kashf al-ẓunūn addressing these two works appear on leaf affixed to 'title page' (p.5).

Hādhā Kitāb al-baḥr al-mawrūd fī al-mawāthīq wa-al-ʻuhūd /

Mode of access: Internet.

Kitāb al-minaḥ al-fikrīyah ʻalá matn al-Jazarīyah /

Mode of access: Internet.