424 research outputs found

    Diagonalization of multicomponent wave equations with a Born-Oppenheimer example

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    A general method to decouple multicomponent linear wave equations is presented. First, the Weyl calculus is used to transform operator relations into relations between c-number valued matrices. Then it is shown that the symbol representing the wave operator can be diagonalized systematically up to arbitrary order in an appropriate expansion parameter. After transforming the symbols back to operators, the original problem is reduced to solving a set of linear uncoupled scalar wave equations. The procedure is exemplified for a particle with a Born-Oppenheimer-type Hamiltonian valid through second order in h. The resulting effective scalar Hamiltonians are seen to contain an additional velocity-dependent potential. This contribution has not been reported in recent studies investigating the adiabatic motion of a neutral particle moving in an inhomogeneous magnetic field. Finally, the relation of the general method to standard quantum-mechanical perturbation theory is discussed

    Atypical chemokine receptor 4 shapes activated B cell fate

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    Activated B cells can initially differentiate into three functionally distinct fates-early plasmablasts (PBs), germinal center (GC) B cells, or early memory B cells-by mechanisms that remain poorly understood. Here, we identify atypical chemokine receptor 4 (ACKR4), a decoy receptor that binds and degrades CCR7 ligands CCL19/CCL21, as a regulator of early activated B cell differentiation. By restricting initial access to splenic interfollicular zones (IFZs), ACKR4 limits the early proliferation of activated B cells, reducing the numbers available for subsequent differentiation. Consequently, ACKR4 deficiency enhanced early PB and GC B cell responses in a CCL19/CCL21-dependent and B cell-intrinsic manner. Conversely, aberrant localization of ACKR4-deficient activated B cells to the IFZ was associated with their preferential commitment to the early PB linage. Our results reveal a regulatory mechanism of B cell trafficking via an atypical chemokine receptor that shapes activated B cell fate

    Adiabatic motion of a neutral spinning particle in an inhomogeneous magnetic field

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    The motion of a neutral particle with a magnetic moment in an inhomogeneous magnetic field is considered. This situation, occurring, for example, in a Stern-Gerlach experiment, is investigated from classical and semiclassical points of view. It is assumed that the magnetic field is strong or slowly varying in space, i.e., that adiabatic conditions hold. To the classical model, a systematic Lie-transform perturbation technique is applied up to second order in the adiabatic-expansion parameter. The averaged classical Hamiltonian contains not only terms representing fictitious electric and magnetic fields but also an additional velocity-dependent potential. The Hamiltonian of the quantum-mechanical system is diagonalized by means of a systematic WKB analysis for coupled wave equations up to second order in the adiabaticity parameter, which is coupled to Planck’s constant. An exact term-by-term correspondence with the averaged classical Hamiltonian is established, thus confirming the relevance of the additional velocity-dependent second-order contribution

    Epidemiology of Kaposi’s sarcoma in sub-Saharan Africa

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    Kaposi’s sarcoma (KS) has become a common AIDS-defining cancer in sub-Saharan Africa. Kaposi’s sarcoma-associated human herpesvirus strongly modulated by HIV-related immune suppression are the principal causes of this cancer. No other risk factors have been identified as playing a strong role. HIV prevention programs and good coverage of antiretroviral therapy (ART) in developed countries resulted in a remarkable decline in HIV-KS incidence and better KS prognosis. By contrast, in sub-Saharan Africa, population ART rollout has lagged, but clinical studies have shown positive results in reduction of KS incidence and better KS prognosis. However, the effect of ART rollout in relation to population KS incidence is unclear. We describe the incidence of KS in sub-Saharan Africa, in four time-periods, (1) before 1980 (before HIV/AIDS era); (2) 1981–2000 (early HIV/AIDS era, limited or no ART coverage); (3) 2001–2010 (early ART coverage period); and (4) 2011–2016 (fair to good ART coverage period). We used KS incidence data available from WHO-International Agency for Research on Cancer (IARC) publications and the Africa Cancer Registry Network. National HIV prevalence and ART coverage data were derived from UNAIDS/WHO. A rapid increase in KS incidence was observed throughout sub-Saharan Africa as the HIV epidemic progressed, reaching peak incidences in Period 2 (pre-ART rollout) of 50.8 in males and 20.3 per 100 000 in females (Zimbabwe, Harare). The overall unweighted average decline in KS incidence between 2000 and 2010 and 2011–2016 was 27%, but this decline was not statistically significant across the region. ART rollout coincides with a decline in KS incidence across several regions in sub-Saharan Africa. The importance of other risk factors such as reductions in HIV incidence could not be ascertained

    Lifestyle factors associated with sex differences in Kaposi sarcoma incidence among adult black South Africans : A case-control study

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    Kaposi Sarcoma (KS) is endemic in several countries in Southern and Eastern Africa, relatively rare worldwide but a leading cancer among people living with HIV. KS has always been more common in adult males than females. We assessed the prevalence of known cancer modifying factors (parity, hormonal contraceptive use in females, sex-partners, smoking and alcohol consumption in both sexes), and their relationship to KS, and whether any of these could account for the unequal KS sex ratios. We calculated logistic regression case-control adjusted odds ratios (ORadj), and 95% confidence intervals (95%CI), between KS and each of the modifying factors, using appropriate comparison controls. Controls were cancer types that had no known relationship to exposures of interest (infection or alcohol or smoking or contraceptive use). The majority of the 1275 KS cases were HIV positive (97%), vs. 15.7% in 10,309 controls. The risk of KS among those with HIV was high in males (ORadj=116.70;95%CI=71.35-190.88) and females (ORadj=93.91;95%CI=54.22-162.40). Among controls, the prevalence of smoking and alcohol consumption was five and three times higher in males vs. females. We found a positive association between KS and heavy vs. non-drinking (ORadj=1.31;95%CI=1.03-1.67), and in current heavy vs. never smokers (ORadj=1.82;95%CI=1.07-3.10). These associations remained positive for alcohol consumption (but with wider CIs) after stratification by sex, and restriction to HIV positive participants. We found no evidence of interactions of smoking and alcohol by sex. Smoking and alcohol consumption may provide a possible explanation for the KS sex differences, given both exposures are more common in men, but confounding and bias cannot be fully ruled out. The role smoking and alcohol play in relation to viral loads of HIV/KSHV, differences in immunological responses or other genetic differences between males and females warrant further studies

    Kaposi sarcoma-associated herpesvirus, HIV-1 and Kaposi sarcoma risk in black South Africans diagnosed with cancer during antiretroviral treatment rollout

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    Abstract Kaposi sarcoma-associated herpesvirus (KSHV) causes Kaposi sarcoma (KS). The risk of KS is amplified in HIV-immunosuppressed individuals and antiretroviral therapy (ART) reduces KS incidence. Reliable data on the relationship between these factors are lacking in Africa. We used questionnaires and serum from 7886 black South Africans (18-74 years) with incident cancer, recruited between 1995 and 2016. ART rollout started in 2004. We measured associations between KS, HIV-1 and KSHV before and after ART rollout. We measured seropositivity to HIV-1, KSHV latency-associated nuclear antigen (LANA) and glycoprotein (K8.1) and calculated case-control-adjusted odds ratios (ORadj) and 95CI) in relation to KS and KSHV infection, before (1995-2004), early (2005-2009) and late (2010-2016) ART rollout periods. KSHV seropositivity among 1237 KS cases was 98649 controls, KSHV seropositivity was higher in males (ORadj = 1.4 [95.23-1.52]), in persons with HIV, (ORadj = 4.2 [95.74-4.73]) and lower in high school leavers (ORadj = 0.7 [95.59-0.83]). KSHV seropositivity declined over the three ART rollout periods (37 288 Ptren

    Ranking lifestyle risk factors for cervical cancer among black women : A case-control study from Johannesburg, South Africa

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    BACKGROUND: Aside from human papillomavirus (HPV), the role of other risk factors in cervical cancer such as age, education, parity, sexual partners, smoking and human immunodeficiency virus (HIV) have been described but never ranked in order of priority. We evaluated the contribution of several known lifestyle co-risk factors for cervical cancer among black South African women. METHODS: We used participant data from the Johannesburg Cancer Study, a case-control study of women recruited mainly at Charlotte Maxeke Johannesburg Academic Hospital between 1995 and 2016. A total of 3,450 women in the study had invasive cervical cancers, 95% of which were squamous cell carcinoma. Controls were 5,709 women with cancers unrelated to exposures of interest. Unconditional logistic regression models were used to calculate adjusted odds ratios (ORadj) and 95% confidence intervals (CI). We ranked these risk factors by their population attributable fractions (PAF), which take the local prevalence of exposure among the cases and risk into account. RESULTS: Cervical cancer in decreasing order of priority was associated with (1) being HIV positive (ORadj = 2.83, 95% CI = 2.53-3.14, PAF = 17.6%), (2) lower educational attainment (ORadj = 1.60, 95% CI = 1.44-1.77, PAF = 16.2%), (3) higher parity (3+ children vs 2-1 children (ORadj = 1.25, 95% CI = 1.07-1.46, PAF = 12.6%), (4) hormonal contraceptive use (ORadj = 1.48, 95% CI = 1.24-1.77, PAF = 8.9%), (5) heavy alcohol consumption (ORadj = 1.44, 95% CI = 1.15-1.81, PAF = 5.6%), (6) current smoking (ORadj = 1.64, 95% CI = 1.41-1.91, PAF = 5.1%), and (7) rural residence (ORadj = 1.60, 95% CI = 1.44-1.77, PAF = 4.4%). CONCLUNSION: This rank order of risks could be used to target educational messaging and appropriate interventions for cervical cancer prevention in South African women
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