Segmental approach to the problems of venous thromboembolism

Many problems in the management of venous thromboembolism remain unsolved because there has been a failure to undertake adequate study of the correlation of clinical and pathological events, and to determine the natural history and prognosis of the disease against which the results of treatment may be measured.This thesis is based on study of a large series of cases of venous thromboembolism in which the pattern of venous involvement was determined by venography and /or surgical exploration. From the results of this study it is concluded that a segmental concept of venous thromboembolism is fundamental to the understanding of the clinical manifestations and to a rational approach to the many problems that are encountered.The study demonstrates the arrangements of the collateral circulation which determine the varying clinical picture with venous occlusion at different levels in the deep venous system. The collateral circulation to the femoro- popliteal segment is always adequate and venous insufficiency does not result. In the iliofemoral segment, the collateral arrangements are inadequate and venous insufficiency results.Contrary to popular belief thrombosis in the iliofemoral venous segment is frequently primary not secondary to propagation from the lower leg. Thrombosis of the upper segment is not only the most important type of thrombosis in regard to leg morbidity but is the common source of major pulmonary embolism. On the basis of the results of these studies a rational approach to treatment is proposed, emphasis being placed on the importance of venography in diagnosis and management

Photooxidation of 2-methyl-3-buten-2-ol (MBO) as a potential source of secondary organic aerosol

2-Methyl-3-buten-2-ol (MBO) is an important biogenic hydrocarbon emitted in large quantities by pine forests. Atmospheric photooxidation of MBO is known to lead to oxygenated compounds, such as glycolaldehyde, which is the precursor to glyoxal. Recent studies have shown that the reactive uptake of glyoxal onto aqueous particles can lead to formation of secondary organic aerosol (SOA). In this work, MBO photooxidation under high- and low-NO_x conditions was performed in dual laboratory chambers to quantify the yield of glyoxal and investigate the potential for SOA formation. The yields of glycolaldehyde and 2-hydroxy-2-methylpropanal (HMPR), fragmentation products of MBO photooxidation, were observed to be lower at lower NO_x concentrations. Overall, the glyoxal yield from MBO photooxidation was 25% under high-NO_x and 4% under low-NO_x conditions. In the presence of wet ammonium sulfate seed and under high-NO_x conditions, glyoxal uptake and SOA formation were not observed conclusively, due to relatively low (<30 ppb) glyoxal concentrations. Slight aerosol formation was observed under low-NO_x and dry conditions, with aerosol mass yields on the order of 0.1%. The small amount of SOA was not related to glyoxal uptake, but is likely a result of reactions similar to those that generate isoprene SOA under low-NO_x conditions. The difference in aerosol yields between MBO and isoprene photooxidation under low-NO_x conditions is consistent with the difference in vapor pressures between triols (from MBO) and tetrols (from isoprene). Despite its structural similarity to isoprene, photooxidation of MBO is not expected to make a significant contribution to SOA formation

A Diet Enriched in Docosahexanoic Acid Exacerbates Brain Parenchymal Extravasation of Apo B Lipoproteins Induced by Chronic Ingestion of Saturated Fats

Chronic ingestion of saturated fatty acids (SFAs) was previously shown to compromise blood-brain barrier integrity, leading to brain parenchymal extravasation of apolipoprotein B (apo B) lipoproteins enriched in amyloid beta. In contrast, diets enriched in mono- or polyunsaturated (PUFA) oils had no detrimental effect. Rather, n3 and n6 oils generally confer protection via suppression of inflammation. This study investigated in wild-type mice if a PUFA diet enriched in docosahexanoic acid (DHA) restored blood-brain barrier integrity and attenuated parenchymal apo B abundance induced by chronic ingestion of SFA. Cerebrovascular leakage of apo B was quantitated utilising immunofluorescent staining. The plasma concentration of brain-derived S100β was measured as a marker of cerebrovascular inflammation. In mice fed SFA for 3 months, provision thereafter of a DHA-enriched diet exacerbated parenchymal apo B retention, concomitant with a significant increase in plasma cholesterol. In contrast, provision of a low-fat diet following chronic SFA feeding had no effect on SFA-induced parenchymal apo B. The findings suggest that in a heightened state of cerebrovascular inflammation, the provision of unsaturated fatty acids may be detrimental, possibly as a consequence of a greater susceptibility for oxidation

The AdS/CFT/Unparticle Correspondence

We examine the correspondence between the anti-de Sitter (AdS) description of conformal field theories (CFTs) and the unparticle description of CFTs. We show how unparticle actions are equivalent to holographic boundary actions for fields in AdS, and how massive unparticles provide a new type of infrared cutoff that can be simply implemented in AdS by a soft breaking of conformal symmetry. We also show that processes involving scalar unparticles with dimensions d_s<2 or fermion unparticles with dimensions d_f<5/2 are insensitive to ultraviolet cutoff effects. Finally we show that gauge interactions for unparticles can be described by bulk gauge interactions in AdS and that they correspond to minimal gauging of the non-local effective action, and we compute the fermion unparticle production cross-section.Comment: 26 pages, 1 figur

Comparison of the estimated incidence of acute leptospirosis in the Kilimanjaro Region of Tanzania between 2007-08 and 2012-14

Background: The sole report of annual leptospirosis incidence in continental Africa of 75–102 cases per 100,000 population is from a study performed in August 2007 through September 2008 in the Kilimanjaro Region of Tanzania. To evaluate the stability of this estimate over time, we estimated the incidence of acute leptospirosis in Kilimanjaro Region, northern Tanzania for the time period 2012–2014. Methodology and Principal Findings: Leptospirosis cases were identified among febrile patients at two sentinel hospitals in the Kilimanjaro Region. Leptospirosis was diagnosed by serum microscopic agglutination testing using a panel of 20 Leptospira serovars belonging to 17 separate serogroups. Serum was taken at enrolment and patients were asked to return 4–6 weeks later to provide convalescent serum. Confirmed cases required a 4-fold rise in titre and probable cases required a single titre of ≥800. Findings from a healthcare utilisation survey were used to estimate multipliers to adjust for cases not seen at sentinel hospitals. We identified 19 (1.7%) confirmed or probable cases among 1,115 patients who presented with a febrile illness. Of cases, the predominant reactive serogroups were Australis 8 (42.1%), Sejroe 3 (15.8%), Grippotyphosa 2 (10.5%), Icterohaemorrhagiae 2 (10.5%), Pyrogenes 2 (10.5%), Djasiman 1 (5.3%), Tarassovi 1 (5.3%). We estimated that the annual incidence of leptospirosis was 11–18 cases per 100,000 population. This was a significantly lower incidence than 2007–08 (p&lt;0.001). Conclusions: We estimated a much lower incidence of acute leptospirosis than previously, with a notable absence of cases due to the previously predominant serogroup Mini. Our findings indicate a dynamic epidemiology of leptospirosis in this area and highlight the value of multi-year surveillance to understand leptospirosis epidemiology

Communications and Related Projects

Contains reports on four research projects

Risk factors for human acute leptospirosis in northern Tanzania

Introduction: Leptospirosis is a major cause of febrile illness in Africa but little is known about risk factors for human infection. We conducted a cross-sectional study to investigate risk factors for acute leptospirosis and Leptospira seropositivity among patients with fever attending referral hospitals in northern Tanzania. Methods: We enrolled patients with fever from two referral hospitals in Moshi, Tanzania, 2012–2014, and performed Leptospira microscopic agglutination testing on acute and convalescent serum. Cases of acute leptospirosis were participants with a four-fold rise in antibody titers, or a single reciprocal titer ≥800. Seropositive participants required a single titer ≥100, and controls had titers &#60;100 in both acute and convalescent samples. We administered a questionnaire to assess risk behaviors over the preceding 30 days. We created cumulative scales of exposure to livestock urine, rodents, and surface water, and calculated odds ratios (OR) for individual behaviors and for cumulative exposure variables. Results: We identified 24 acute cases, 252 seropositive participants, and 592 controls. Rice farming (OR 14.6), cleaning cattle waste (OR 4.3), feeding cattle (OR 3.9), farm work (OR 3.3), and an increasing cattle urine exposure score (OR 1.2 per point) were associated with acute leptospirosis. Conclusions: In our population, exposure to cattle and rice farming were risk factors for acute leptospirosis. Although further data is needed, these results suggest that cattle may be an important source of human leptospirosis. Further investigation is needed to explore the potential for control of livestock Leptospira infection to reduce human disease

Comprehensive Analysis of HLA-A, HLA-B, HLA-C, HLA-DRB1, and HLA-DQB1 Loci and Squamous Cell Cervical Cancer Risk

Variation in human major histocompatibility genes may influence the risk of squamous cell cervical cancer (SCC) by altering the efficiency of the T-cell–mediated immune response to human papillomavirus (HPV) antigens. We used high-resolution methods to genotype human leukocyte antigen (HLA) class I (A, B, and Cw) and class II (DRB1 and DQB1) loci in 544 women with SCC and 542 controls. Recognizing that HLA molecules are codominantly expressed, we focused on co-occurring alleles. Among 137 allele combinations present at >5% in the case or control groups, 36 were significantly associated with SCC risk. All but one of the 30 combinations that increased risk included DQB1*0301, and 23 included subsets of A*0201-B*4402-Cw*0501-DRB1*0401-DQB1*0301. Another combination, B*4402-DRB1*1101-DQB1*0301, conferred a strong risk of SCC (odds ratio, 10.0; 95% confidence interval, 3.0–33.3). Among the six combinations that conferred a decreased risk of SCC, four included Cw*0701 or DQB1*02. Most multilocus results were similar for SCC that contained HPV16; a notable exception was A*0101-B*0801-Cw*0701-DRB1*0301-DQB1*0201 and its subsets, which were associated with HPV16-positive SCC (odds ratio, 0.5; 95% confidence interval, 0.3–0.9). The main multilocus associations were replicated in studies of cervical adenocarcinoma and vulvar cancer. These data confirm that T helper and cytotoxic T-cell responses are both important cofactors with HPV in cervical cancer etiology and indicate that co-occurring HLA alleles across loci seem to be more important than individual alleles. Thus, certain co-occurring alleles may be markers of disease risk that have clinical value as biomarkers for targeted screening or development of new therapies

The effect of the systemic inflammatory response on plasma vitamin 25 (OH) D concentrations adjusted for albumin

&lt;b&gt;Aim&lt;/b&gt;&lt;p&gt;&lt;/p&gt; To examine the relationship between plasma 25(OH)D, CRP and albumin concentrations in two patient cohorts.&lt;p&gt;&lt;/p&gt; &lt;b&gt;Methods&lt;/b&gt;&lt;p&gt;&lt;/p&gt; 5327 patients referred for nutritional assessment and 117 patients with critical illness were examined. Plasma 25 (OH) D concentrations were measured using standard methods. Intra and between assay imprecision was &#60;10%.&lt;p&gt;&lt;/p&gt; &lt;b&gt;Result&lt;/b&gt;&lt;p&gt;&lt;/p&gt; In the large cohort, plasma 25 (OH) D was significantly associated with CRP (rs = −0.113, p&#60;0.001) and albumin (rs = 0.192, p&#60;0.001). 3711 patients had CRP concentrations ≤10 mg/L; with decreasing albumin concentrations ≥35, 25–34 and &#60;25 g/l, median concentrations of 25 (OH) D were significantly lower from 35 to 28 to 14 nmol/l (p&#60;0.001). This decrease was significant when albumin concentrations were reduced between 25–34 g/L (p&#60;0.001) and when albumin &#60;25 g/L (p&#60;0.001). 1271 patients had CRP concentrations between 11–80 mg/L; with decreasing albumin concentrations ≥35, 25–34 and &#60;25 g/l, median concentrations of 25 (OH) D were significantly lower from 31 to 24 to 19 nmol/l (p&#60;0.001). This decrease was significant when albumin concentration were 25–34 g/L (p&#60;0.001) and when albumin &#60;25 g/L (p&#60;0.001). 345 patients had CRP concentrations &#62;80 mg/L; with decreasing albumin concentrations ≥35, 25–34 and &#60;25 g/l, median concentrations of 25 (OH) D were not significantly altered varying from 19 to 23 to 23 nmol/l. Similar relationships were also obtained in the cohort of patients with critical illness.&lt;p&gt;&lt;/p&gt; &lt;b&gt;Conclusion&lt;/b&gt;&lt;p&gt;&lt;/p&gt; Plasma concentrations of 25(OH) D were independently associated with both CRP and albumin and consistent with the systemic inflammatory response as a major confounding factor in determining vitamin D status.&lt;p&gt;&lt;/p&gt