Enteral Vancomycin to Eliminate MRSA Carriership of the Digestive Tract in Critically Ill Patients

Background: Carriership with methicillin resistant Staphylococcus aureus (MRSA) is a risk for the development of secondary infections in critically ill patients. Previous studies suggest that enteral vancomycin is able to eliminate enteral carriership with MRSA. Data on individual effects of this treatment are lacking. Methods: Retrospective analysis of a database containing 15 year data of consecutive patients from a mixed medical-(cardio)surgical 18 bedded intensive care unit was conducted. All consecutive critically ill patients with enteral MRSA carriership detected in throat and/or rectal samples were collected. We analyzed those with follow-up cultures to determine the success rate of enteral vancomycin. Topical application of 2% vancomycin in a sticky oral paste was performed combined with a vancomycin solution of 500 mg four times daily in the nasogastric tube. This treatment was added to a regimen of selective digestive tract decontamination (SDD) to prevent ICU acquired infection. Results: Thirteen patients were included. The mean age was 65 years and the median APACHE II score was 21. MRSA was present in the throat in 8 patients and in both throat and rectum in 5 patients. In all patients MRSA was successfully eliminated from both throat and rectum, which took 2–11 days with a median duration until decontamination of 4 days. Secondary infections with MRSA did not occur. Conclusions: Topical treatment with vancomycin in a 2% sticky oral paste four times daily in the nasogastric tube was effective in all patients in the elimination of MRSA and prevented secondary MRSA infections

3C 220.3: a radio galaxy lensing a submillimeter galaxy

Herschel Space Observatory photometry and extensive multiwavelength followup have revealed that the powerful radio galaxy 3C 220.3 at z=0.685 acts as a gravitational lens for a background submillimeter galaxy (SMG) at z=2.221. At an observed wavelength of 1mm, the SMG is lensed into three distinct images. In the observed near infrared, these images are connected by an arc of 1.8" radius forming an Einstein half-ring centered near the radio galaxy. In visible light, only the arc is apparent. 3C 220.3 is the only known instance of strong galaxy-scale lensing by a powerful radio galaxy not located in a galaxy cluster and therefore it offers the potential to probe the dark matter content of the radio galaxy host. Lens modeling rejects a single lens, but two lenses centered on the radio galaxy host A and a companion B, separated by 1.5", provide a fit consistent with all data and reveal faint candidates for the predicted fourth and fifth images. The model does not require an extended common dark matter halo, consistent with the absence of extended bright X-ray emission on our Chandra image. The projected dark matter fractions within the Einstein radii of A (1.02") and B (0.61") are about 0.4 +/- 0.3 and 0.55 +/- 0.3. The mass to i-band light ratios of A and B, M/L ~ 8 +/- 4 Msun/Lsun, appear comparable to those of radio-quiet lensing galaxies at the same redshift in the CASTLES, LSD, and SL2S samples. The lensed SMG is extremely bright with observed f(250um) = 440mJy owing to a magnification factor mu~10. The SMG spectrum shows luminous, narrow CIV 154.9nm emission, revealing that the SMG houses a hidden quasar in addition to a violent starburst. Multicolor image reconstruction of the SMG indicates a bipolar morphology of the emitted ultraviolet (UV) light suggestive of cones through which UV light escapes a dust-enshrouded nucleus.Comment: 17 pages, 14 Figures, accepted for publication in Ap

Comparing quality of dying and death perceived by family members and nurses for patients dying in US and Dutch ICUs

BACKGROUND: The Quality of Dying and Death (QODD) questionnaire is used as a selfreported measure to allow families and clinicians to assess patients' quality of dying and death. We evaluated end-of-life (EOL) experiences as measured by the QODD completed by families and nurses in the United States and the Netherlands to explore similarities and differences in these experiences and identify opportunities for improving EOL care. METHODS: Questionnaire data were gathered from family members of patients dying in the ICU and nurses caring for these patients. In The Netherlands, data were gathered in three teaching hospitals, and data was gathered from 12 sites participating in a randomized trial in the United States. The QODD consists of 25 items and has been validated in the United States. RESULTS: Data from 446 patients were analyzed (346 in the United States and 100 in the Netherlands). Dutch patients were older than those in the United States (72 + 10.2 years vs 65 + 16.0 years; P <.0025). The family-assessed overall QODD score was the same in both countries: the Netherlands = median, 9; interquartile range (IQR), 8-10 and the United States = median, 8; IQR, 5-10. US family members rated the quality of two items higher than did the Netherlands families: "time spent with loved ones" and "time spent alone." Nurseassessed QODD ratings varied: the single-item QODD summary score was significantly higher in the Netherlands (the Netherlands: median, 9; IQR, 8-10 vs the United States: median, 7; IQR, 5-8; P <.0025), whereas the QODD total score was higher in the United States (the Netherlands: median, 6.9; IQR, 5.5-7.6 vs the United States: median, 7.1; IQR, 5.88.4; P = .014), although it did not meet our criteria for statistical significance. Of the 22 nurse-assessed items, 10 were significantly different between the Netherlands and the United States, with eight having higher scores in the United States and 2 having higher scores in the Netherlands. CONCLUSIONS: The QODD was rated similarly by family members in the United States and the Netherlands but varied when assessed by nurses. These differences may be due to organizational or cultural differences between the two countries or to expectations of respondents

Relativistically rotating dust

Dust configurations play an important role in astrophysics and are the simplest models for rotating bodies. The physical properties of the general--relativistic global solution for the rigidly rotating disk of dust, which has been found recently as the solution of a boundary value problem, are discussed.Comment: 18 pages, 11 figure

SDSS J092455.87+021924.9: an Interesting Gravitationally Lensed Quasar from the Sloan Digital Sky Survey

We report the discovery of a new gravitationally lensed quasar from the Sloan Digital Sky Survey, SDSS J092455.87+021924.9 (SDSS J0924+0219). This object was selected from among known SDSS quasars by an algorithm that was designed to select another known SDSS lensed quasar (SDSS 1226-0006A,B). Five separate components, three of which are unresolved, are identified in photometric follow-up observations obtained with the Magellan Consortium's 6.5m Walter Baade telescope at Las Campanas Observatory. Two of the unresolved components (designated A and B) are confirmed to be quasars with z=1.524; the velocity difference is less than 100 km sec^{-1} according to spectra taken with the W. M. Keck Observatory's Keck II telescope on Mauna Kea. A third stellar component, designated C, has the colors of a quasar with redshift similar to components A and B. The maximum separation of the point sources is 1.78". The other two sources, designated G and D, are resolved. Component G appears to be the best candidate for the lensing galaxy. Although component D is near the expected position of the fourth lensed component in a four image lens system, its properties are not consistent with being the image of a quasar at z~1.5. Nevertheless, the identical redshifts of components A and B and the presence of component C strongly suggest that this object is a gravitational lens. Our observations support the idea that a foreground object reddens the fourth lensed component and that another unmodeled effect (such as micro- or milli-lensing) demagnificates it, but we cannot rule out the possibility that SDSS0924+0219 is an example of the relatively rare class of ``three component'' lens systems.Comment: 24 pages, 6 figures, accepted by A

Численный анализ распространения и усиления волн цунами на северо-западном шельфе Черного моря

Выполнен численный анализ распространения длинных волн в северо-западной части Черного моря. Рассмотрено 10 возможных зон сейсмической генерации цунами. Расчеты выполнены на сетке с шагом 500 м. Показано, что положение очага цунами существенно влияет на распределение высот волн вдоль побережья. Как правило, наиболее интенсивные волны формируются у ближайшего участка берега. Землетрясения в Южнобережной сейсмической зоне не могут привести к цунамиопасности в западной части моря. Только сильные землетрясения в северо-западной части способны вызывать заметные колебания уровня Черного моря. Период цунами в районе Одессы составляет около 1 ч и зависит от магнитуды землетрясения, в районе Севастополя он в 2 – 3 раза меньше. В большинстве пунктов побережья экстремальные подъемы и понижения уровня моря не превышают по абсолютной величине начального смещения поверхности моря в очаге цунами. Для отдельных участков побережья Румынии и западного побережья Крыма наблюдается некоторое усиление волн, излученных из зон генерации, расположенных в более глубоководной части исследуемого района. С ростом магнитуды землетрясения усиление волн у берега становится более значительным.Виконаний чисельний аналіз розповсюдження довгих хвиль у північно-західній частині Чорного моря. Розглянуто 10 можливих зон сейсмічної генерації цунамі. Розрахунки виконані на сітці з кроком 500 м. Показано, що положення осередку цунамі суттєво впливає на розподіл висот хвиль уздовж побережжя. Як правило, найінтенсивніші хвилі формуються близько найближчої ділянки берега. Землетруси в південнобережній сейсмічній зоні не можуть призвести до цунамонебезпеки в західній частині моря. Лише сильні землетруси в північнозахідній частині здатні викликати помітні коливання рівня Чорного моря. Період цунамі в районі Одеси складає близько 1 години і залежить від магнітуди землетрусу, в районі Севастополя він в 2 – 3 рази менший. У більшості пунктів побережжя екстремальні підйоми і пониження рівня моря не перевищують за абсолютною величиною початкового зсуву поверхні моря в осередку цунамі. Для окремих ділянок побережжя Румунії і західного побережжя Криму спостерігається деяке посилення хвиль, які випромінюють із зон генерації, розташованих в більш глибоководній частині досліджуваного району. Із зростанням магнітуди землетрусу посилення хвиль біля берега стає значнішим.Numerical analysis of long wave propagation in the Black Sea northwestern part is carried out. Ten possible zones of tsunami seismic generation are considered. The calculation are performed on the grid with a step 500 m. It is shown that location of tsunami source effects essentially the distribution of waves’ heights along the coast. As a rule, the most intensive waves are formed in the part closest to the coast. Earthquakes in the South coast seismic zone can not result in tsunami threat in the western part of the sea. Only strong earthquakes in the Black Sea northwestern part can generate noticeable sea level oscillations. Tsunami period near Odessa is about one hour and it depends on the earthquake magnitude. In the Sevastopol region it is 2 – 3 times lower. In the majority of coastal points extreme rises and falls of the sea level do not exceed the absolute value of the initial sea surface elevation in the tsunami source. Some intensification of the waves generated in deeper regions of the area under study is possible in certain parts of the Romanian coast and the Crimean western coast. The wave intensification near the coast grows with the increase of the earthquake magnitude

Математичне програмування

Викладено основи математичного програмування - науки, що займається оптимізаційними методами, які слугують кількісним обґрунтуванням оптимальних управлінських рішень в економіці. Розглянуто основні поняття і методологічні принципи математичного програмування, математичні методи оптимізації (лінійне, дробово-лінійне, цілочислове, нелінійне, динамічне програмування). Матеріал викладено на порівняно елементарному рівні, доступно- му студентам, які знайомі з курсом математики для економістів. Методи, що розглядаються в посібнику, ілюструються великою кількістю прикладів. Посібник має на меті навчити студентів застосовувати математику та обчислювальну техніку для обґрунтування оптимальних економічних рішен

A novel bispecific antibody for EGFR-directed blockade of the PD-1/PD-L1 immune checkpoint

PD-L1-blocking antibodies produce significant clinical benefit in selected cancer patients by reactivating functionally-impaired antigen-experienced anticancer T cells. However, the efficacy of current PD-L1-blocking antibodies is potentially reduced by on-target/off-tumor' binding to PD-L1 widely expressed on normal cells. This lack of tumor selectivity may induce a generalized activation of all antigen-experienced T cells which may explain the frequent occurrence of autoimmune-related adverse events during and after treatment. To address these issues, we constructed a bispecific antibody (bsAb), designated PD-L1xEGFR, to direct PD-L1-blockade to EGFR-expressing cancer cells and to more selectively reactivate anticancer T cells. Indeed, the IC50 of PD-L1xEGFR for blocking PD-L1 on EGFR(+) cancer cells was similar to 140 fold lower compared to that of the analogous PD-L1-blocking bsAb PD-L1xMock with irrelevant target antigen specificity. Importantly, activation status, IFN-gamma production, and oncolytic activity of anti-CD3xanti-EpCAM-redirected T cells was enhanced when cocultured with EGFR-expressing carcinoma cells. Similarly, the capacity of PD-L1xEGFR to promote proliferation and IFN-gamma production by CMVpp65-directed CD8(+) effector T cells was enhanced when cocultured with EGFR-expressing CMVpp65-transfected cancer cells. In contrast, the clinically-used PD-L1-blocking antibody MEDI4736 (durvalumab) promoted T cell activation indiscriminate of EGFR expression on cancer cells. Additionally, in mice xenografted with EGFR-expressing cancer cells In-111-PD-L1xEGFR showed a significantly higher tumor uptake compared to In-111-PD-L1xMock. In conclusion, PD-L1xEGFR blocks the PD-1/PD-L1 immune checkpoint in an EGFR-directed manner, thereby promoting the selective reactivation of anticancer T cells. This novel targeted approach may be useful to enhance efficacy and safety of PD-1/PD-L1 checkpoint blockade in EGFR-overexpressing malignancies

COVID-19 vaccination in patients with immune thrombocytopenia

Immune thrombocytopenia (ITP) is an acquired autoimmune disorder characterized by low platelet count and increased bleeding risk. COVID-19 vaccination has been described as risk factor for de novo ITP, but the effects of COVID-19 vaccination in patients with ITP are unknown. Our aims were to investigate the effects of COVID-19 vaccination in ITP patients on platelet count, bleeding complications and ITP exacerbation (any of: ≥50% decline in platelet count; or nadir platelet count 20% decrease from baseline; or use of rescue therapy). Platelet counts of ITP patients and healthy controls were collected immediately before, 1 and 4 weeks after first and second vaccination. Linear mixed-effects modelling was applied to analyze platelet counts over time. We included 218 ITP patients (50.9% female, mean age 55 years and median platelet count of 106x109/L) and 200 healthy controls (60.0% female, mean age 58 years and median platelet count of 256x109/L). Platelet counts decreased by 6.3% after vaccination. We observed no difference in decrease between the groups. Thirty ITP patients (13.8%, 95%CI 9.5%-19.1%) had an exacerbation and 5 (2.2%, 95%CI 0.7%-5.3%) suffered from a bleeding event. Risk factors for ITP exacerbation were platelet count <50x109/L (OR 5.3, 95%CI 2.1-13.7), ITP treatment at time of vaccination (OR 3.4, 95%CI 1.5-8.0) and age (OR 0.96 per year, 95%CI 0.94-0.99). Our study highlights safety of COVID-19 vaccination in ITP patients and importance of close monitoring platelet counts in a subgroup of ITP patients. ITP patients with exacerbation responded well on therapy

Infectious Bronchitis Virus induces acute interferon-gamma production through polyclonal stimulation of chicken leukocytes

AbstractInfectious Bronchitis Virus, a member of the Coronaviridae, is a respiratory pathogen in poultry. We found that in vitro stimulation with IBV resulted in ChIFN-γ production in splenocytes of both infected birds and uninfected birds. The non-specific stimulation did not occur when other avian viruses or other coronaviruses were used or when mammalian cells were stimulated with IBV. Inactivation of IBV reduced ChIFN-γ production, but ChIFN-γ remained elevated compared to unstimulated cells. An increase in ChIFN-γ mRNA was detected in splenocytes from IBV-infected and uninfected chickens as early as 1 h after stimulation with IBV. These results indicate that IBV acts as a polyclonal stimulus, inducing a rapid production of IFN-γ even without previous exposure to the virus