Abstract Background Ovarian cancer is mostly diagnosed in the elderly woman who is likely to have comorbid disease and to take several comedications on a regular basis. Aim of this study was to ...evaluate the influence of polypharmacy on grade III/IV toxicity, prior discontinuation of chemotherapy and survival. Patients and methods In this individual participant data meta-analysis the original data of three phase II/III studies of the North-Eastern German Society of Gynecological Oncology (NOGGO) were analyzed using multivariate logistic and Cox regression. Results Overall, 1213 patients with recurrent ovarian cancer were included in these analyses. An increasing amount of medication was associated with overall grade III/IV toxicity (p < 0.001; OR 1.120), and hematological (p < 0.001; OR 1.056) and non-hematological (p < 0.001; OR 1.134) toxicities. Prior discontinuation of chemotherapy was not influenced by an increasing amount of medication (p = 0.196). There was no association of polypharmacy with overall survival (p = 0.068). Conclusion As polypharmacy does not influence survival ovarian cancer patients taking several comedications may be included in clinical trials and should not be deprived of adequate cancer treatment. However, a thorough monitoring is mandatory due to the increased risk of toxicities.
Dietary iron and heme, likely through their effect on gut commensal bacteria and colonic barrier function, have been shown to modulate colonic inflammation in animal models of colitis. Nonetheless, ...the link between dietary total and heme iron and risk of Crohn's disease (CD) and ulcerative colitis (UC) has not been previously explored.
We conducted a prospective cohort study of 165,331 U.S. women enrolled in the Nurses' Health Study and Nurses' Health Study II. Dietary information was collected using a validated food frequency questionnaire at baseline (1984) and updated every 2 to 4 years. Self-reported CD and UC diagnoses were confirmed through medical records review. We used Cox proportional hazard models to calculate hazard ratios and 95% confidence intervals while adjusting for potential confounders. In a case-control study nested within these cohorts, we evaluated the interaction between single-nucleotide polymorphisms associated with genome-wide susceptibility to CD and UC and dietary total and heme iron intake on risk of CD and UC using logistic regression modeling.
Through 2011, over 3,038,049 person-years of follow-up, we documented 261 incident cases of CD and 321 incident cases of UC. Dietary heme iron was nonsignificantly associated with increased risk of UC (Ptrend = 0.12). This association seemed to be modified by the UC susceptibility locus, rs1801274, a coding variant in the FcγRIIA gene (Pinteraction = 7.00E-05). In contrast, there was no association between dietary heme iron and risk of CD (Ptrend = 0.67). We also did not observe an association between total dietary intake of iron and risk of CD or UC (All Ptrend > 0.35).
In 2 large prospective cohort studies, dietary total and heme iron were not associated with risk of CD or UC. Our suggestive finding that the association between dietary heme iron intake and risk of UC may be modified by a coding variant in FcγRIIA gene warrants additional investigation.
A major obstacle to using recombinant adenoviral vectors in gene therapy is the natural ability of human adenovirus to activate the classical and alternate complement pathways. These innate immune ...responses contribute to hepatic adenoviral uptake following systemic delivery and enhance the humoral immune responses associated with adenoviral infection.
A recombinant Ad5 vector was genetically modified to display a peptide sequence ("rH17d'"), a known inhibitor of the classical complement pathway. The replication-defective vectors Ad5.HVR2-rH17d' and Ad5.HVR5-rH17d' were constructed by engineering the rH17d' peptide into the hypervariable region (HVR)-2 or HVR5 of their major capsid protein hexon. Control Ad5 vectors were created by incorporation of a 6-histidine (His6)-insert in either HVR2 or HVR5 (Ad5.HVR2-His6 and Ad5.HVR5-His6, respectively). All vectors encoded CMV promoter-controlled firefly luciferase (Luc). The four vectors were evaluated in TIB76 mouse liver cells and immunocompetent mice to compare infectivity and liver sequestration, respectively.
In vitro studies demonstrated that preincubation of all the Ad5 vectors with fresh serum significantly increased their gene transfer relative to preincubation with PBS except Ad5.HVR5-rH17d', whose infectivity of liver cells showed no serum-mediated enhancement. In line with that, mice injected with Ad5.HVR2-rH17d' or Ad5.HVR5-rH17d' showed significantly lower luciferase expression levels in the liver as compared to the respective control vectors, whereas efficiency of tumor transduction by rH17d' and His6 vectors following their intratumoral injection was similar.
Displaying a complement-inhibiting peptide on the Ad5 capsid surface by genetic modification of the hexon protein could be a suitable strategy for reducing Ad5 liver tropism (Ad5 sequestration by liver), which may be applicable to other gene therapy vectors with natural liver tropism.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Background An effective cross-cultural doctor-patient communication is vital for health literacy and patient compliance. Building a good relationship with medical staff is also relevant for the ...treatment decision-making process for cancer patients. Studies about the role of a specific migrant background regarding patient preferences and expectations are lacking. We therefore conducted a multicentre prospective survey to explore the needs and preferences of patients with a migrant background (PMB) suffering from gynecological malignancies and breast cancer to evaluate the quality of doctor-patient communication and cancer management compared to non-migrants (NM). Methods This multicentre survey recruited patients with primary or recurrence of breast, ovarian, peritoneal, or fallopian tube cancer. The patients either filled out a paper form, participated via an online survey, or were interviewed by trained staff. A 58-item questionnaire was primarily developed in German and then translated into three different languages to reach non-German-speaking patients. Results A total of 606 patients were included in the study: 54.1% (328) were interviewed directly, 9.1% (55) participated via an online survey, and 36.8% (223) used the paper print version. More than one quarter, 27.4% (166) of the participants, had a migrant background. The majority of migrants and NM were highly satisfied with the communication with their doctors. First-generation migrants (FGM) and patients with breast cancer were less often informed about participation in clinical trials (p < 0.05) and 24.5% of them suggested the help of an interpreter to improve the medical consultation. Second and third-generation migrants (SGM and TGM) experienced more fatigue and nausea than expected. Conclusions Our results allow the hypothesis that training medical staff in intercultural competence and using disease-related patient information in different languages can improve best supportive care management and quality of life in cancer patients with migrant status. Keywords: Migrants, Survey, Doctor-patient relationship, Patient preference, Therapy expectations
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Remote sensing with unmanned aerial vehicles (UAVs) is a fast and cost-efficient tool for mapping and environmental monitoring. The sensors are operated at low flight altitudes, usually below 500 m ...above ground, leading to spatial resolutions up to the centimeter range. This type of data causes new challenges in atmospheric compensation and surface reflectance retrieval. Based on these specific boundary conditions, a new drone based atmospheric correction concept (DROACOR) is proposed, which is designed for currently available UAV based sensors. It is suited for multispectral visible/near infrared sensors as well as hyperspectral instruments covering the 400–1000 nm spectral region or the 400–2500 nm spectrum. The goal of the development is a fully automatic processor which dynamically adjusts to the given instrument and the atmospheric conditions. Optionally, irradiance measurements from simultaneously measured cosine receptors or from in-field reference panels can be taken into account to improve the processing quality by adjusting the irradiance parameter or by performing an in-flight vicarious calibration. Examples of DROACOR processing results are presented for a multispectral image data set and a hyperspectral data set, both acquired at variable flight altitudes. The resulting spectra show the applicability of the methods for both sensor types and an accuracy level below 2.5% reflectance units.
The fragmentation dynamics of the gas-phase, doubly charged camphor molecule, formed by Auger decay following carbon 1s ionisation, using soft X-ray synchrotron radiation, is presented in this work. ...The technique of velocity map imaging combined with a photoelectron-photoion-photoion coincidence (VMI-PEPIPICO) is used for both electron energy and ion momentum (in-sequence) measurements. The experimental study is complemented by molecular dynamics simulation, performed with an
NVT
(moles, volume, and temperature) ensemble. Velocity Verlet algorithms were used for time integration at various internal energies. These simulations validate observed dissociation pathways. From these, we successfully deduce that the internal energy of the doubly charged molecular ion has a significant contribution to the fragmentation mechanism. Notably, a prominent signature of the internal energy was observed in the experimentally determined energies of the neutral fragment in these deferred charge separation pathways, entailing a more detailed theoretical study to uncover the exact dissociation dynamics.
Investigation of the fragmentation of doubly charged camphor molecule following C 1s Auger decay experimentally by VMI-PEPIPICO, supplemented with MD simulations.
Hill's Conjecture states that the crossing number
cr
(
K
n
) of the complete graph
K
n in the plane (equivalently, the sphere) is
1
4
⌊
n
2
⌋
⌊
n
−
1
2
⌋
⌊
n
−
2
2
⌋
⌊
n
−
3
2
⌋
=
n
4
∕
64
+
O
(
n
3
...). Moon proved that the expected number of crossings in a spherical drawing in which the points are randomly distributed and joined by geodesics is precisely
n
4
∕
64
+
O
(
n
3
), thus matching asymptotically the conjectured value of
cr
(
K
n
). Let
cr
P
(
G
) denote the crossing number of a graph
G in the projective plane. Recently, Elkies proved that the expected number of crossings in a naturally defined random projective plane drawing of
K
n is
(
n
4
∕
8
π
2
)
+
O
(
n
3
). In analogy with the relation of Moon's result to Hill's conjecture, Elkies asked if
lim
n
→
∞
cr
P
(
K
n
)
∕
n
4
=
1
∕
8
π
2. We construct drawings of
K
n in the projective plane that disprove this.
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