Background: Heart transplant from controlled donation after circulatory death (cDCD) is an emerging strategy that is rapidly expanding and may help increase the heart donor pool. Materials and Methods: The use of thoracoabdominal normothermic regional perfusion (TANRP) with extracorporeal membrane oxygenation device has allowed to perform cardiac transplantation after cDCD. Several experiences have been carried out in recent years, however the maximum cold ischemia time is still unknown. We present a successful case of heart transplantation using a graft from cDCD from another hospital with 201 minutes of cold ischemia time, the longest published in Europe. Discussion and conclusion: Heart transplant from cDCD could be a good alternative to brain dead donation. This experience suggests than nonlocal cardiac donation in controlled asystole could tolerate long periods of cold ischemia time and break the main barriers in cardiac donation after circulatory death.

Motivated by an important geophysical application, we analyze the nonlinear dynamics of the number of earthquakes per unit time in a given Earth’s surface area. At first, we consider a dynamical model of earthquakes describing their rhythmic behaviour with time delays. This model comprises different earthquake scenarios divided into three types (A, B, and C) accordingly to various system dynamics. We show that the deterministic system contains stable equilibria and a limit cycle whose size drastically depends on the production rate $\alpha$ of earthquakes and their time-delay effect. As this takes place, the frequency of earthquakes possesses an oscillatory behaviour dependent on $\alpha$. To study the role of $\alpha$ in more detail, we have introduced a white Gaussian noise in the governing equation. First of all, we have shown that the dynamical system is stochastically excitable, i.e. it excites larger-amplitude noise-induced fluctuations in the frequency of earthquakes. In addition, these large-amplitude stochastic fluctuations can alternate with small-amplitude fluctuations over time. In other words, the frequency of earthquakes can change its amplitude in an irregular manner under the influence of white noise. Another important effect is how close the current value of $\alpha$ is to its bifurcation point. The closer this value is, the less noise generates large-amplitude fluctuations in the earthquake frequency.

Samya Sen

Let $X$ be a finite or infinite dimensional complex Banach space. We characterize the bounded weighted composition operators between the Bloch type space and the Hardy space on the unit ball of $X$, extending several known results for finite dimensional domains.

Viral infection in cell culture and tissue is modeled with delay reaction-diffusion equations. It is shown that progression of viral infection can be characterized by the viral replication number, time-dependent viral load and the speed of infection spreading. These three characteristics are determined through the original model parameters including the rates of cell infection and of virus production in the infected cells. The clinical manifestations of viral infection, depending on tissue damage, correlate with the speed of infection spreading, while the infectivity of a respiratory infection depends on the viral load in the upper respiratory tract. Parameter determination from the experiments on Delta and Omicron variants allows the estimation of the infection spreading speed and viral load. Different variants of the SARS-CoV-2 infection are compared confirming that Omicron is more infectious and has less severe symptoms than Delta variant. Within the same variant, spreading speed (symptoms) correlates with viral load allowing prognosis of disease progression.

Objective In the Netherlands, antenatal cardiotocography (aCTG) is performed in obstetrician-led care to assess fetal well-being. An innovation project was initiated to evaluate whether aCTG is feasible in non-obstetrician-led care settings. Healthy women received aCTG in midwife-led care if indicated for specific indications. Quality assessment is essential when shifting tasks and responsibilities. Therefore, we aimed to assess the interobserver and intraobserver agreement for aCTG assessments among four professional groups regarding the overall classification and the assessment of the various components of the CTG. Design Prospective study. Sample 47 Dutch primary care midwives, hospital-based midwives, residents, and obstetricians. Methods Ten aCTG traces were assessed twice at a one month interval on baseline heart frequency, accelerations, decelerations, variability and contractions, and overall classification. We used two sets of ten aCTG traces to ensure sufficient variation. Main Outcome Measure Proportion of agreement. Results The proportions of agreement for interobserver agreement on classification of aCTG among the professional groups varied from 0.82 to 0.94, indicating excellent agreement. The proportions of agreement for primary care midwives, hospital-based midwives and obstetricians were slightly higher for intraobserver (0.86 to 0.94) than for interobserver agreement. For various CTG components, the proportions of agreement for interobserver agreement varied from 0.64 (presence of contractions) to 0.98 (baseline heart frequency), indicating good to excellent agreement. Conclusion Excellent agreement for the overall classification and good to excellent agreement for the various components were found in the assessments of aCTG in healthy women, both between and within the different professional groups.

Objectives: To determine if race/ethnicity is an independent predictor of adverse outcomes following diagnosis of primary ovarian cancer. Design: Retrospective study Setting: We utilized data from the Surveillance, Epidemiology, and End Results Program (SEER) database for this study. Population: We studied women with a primary diagnosis of Ovarian Cancer in the SEER database between January 1998 and December 2018. Method: We utilized the nearest neighbor propensity-score matching without replacement in a 1:1 ratio to compare mortality and overall survival following primary ovarian cancer diagnosis between Non-Hispanic Black (NHB) women and a control group of Non-Hispanic White (NHW) women. These women were matched for age, treatment modalities (surgery/irradiation/chemotherapy), laterality, and stage of cancer at presentation. Main Outcomes: The primary outcomes of interest were differences in mortality and survival (in months) among NHB and NHW women Results: We compared 6,801 NHB women with 27, 204 NHW women with primary ovarian cancer. Prior to propensity-score matching, NHB women had a higher mortality rate (56.7%vs.53.5%, p<0.001) and lower survival rate (40.1 vs. 48.9 months<0.001). Following propensity-score matching, there was no difference in the mortality rate between the two groups. (56.7% vs 55.7% p=0.13). However, NHB women had significantly lower survival rates (40.1vs.49.6 months, p < 0.001). Conclusion: Racial disparities in survival following treatment for ovarian cancer persist despite adjusting for age, stage of cancer, and treatment modalities. Further research is warranted to explore patient and systemic factors such as appropriate level of care and follow-up after treatment that might account for these differences.

Background Cell-free DNA, a suitable candidate biomarker forming an emerging field of non-invasive evaluation, has been detected for great clinical applications and increasingly used in obstetrics and gynecology. Objective To describe an intuitive global research trends of cfDNA related literature from a bibliometric perspective, and provide researchers with new research hotspots. Search strategy The literature form PubMed and Web of Science Core Collection (WoSCC) database related to cfDNA from January 1 2017 to December 31 2021 were extracted for co-word and VOSviewer analysis, respectively. Study criteria We selected studies where cfDNA was applied for obstetrics and gynecology, i.e., prenatal diagnosis, preimplantation diagnosis, next generation sequencing technology, mosaicism detection or adverse pregnancy outcomes. Data collection and analysis Bibliographic Item Co-Occurrence Matrix Builder, gCLUTO software and VOSviewer were used to perform bibliometrics analysis. Main results Themes in the third quadrant of strategy diagram, including cell-free nucleic acid sequence analysis for non-invasive prenatal testing and genetic testing, the application of cfDNA in the fields of neoplasms genetics and diagnosis are immature themes which are considered newly emerging themes of cfDNA. VOSviewer results showed the global research trends of cfDNA including authors, institutions, countries, journals and research hotspots. Conclusion By analyzing the research hotspots related to cfDNA, immature themes and emerging hotspots deserve more attention and can be considered as hints when launching new research projects. The five major research hotspots could provide an insight into cfDNA research and valuable information for researchers to identify potential collaborators and partner institutions.

Objectives: The aim of this study is to examine alanine aminotransferase (ALT) levels in a cohort of women diagnosed with gestational diabetes mellitus (GDM) and to investigate the association between elevated ALT and pregnancy outcomes. Design: A retrospective cross-sectional study. Setting: Cork University Maternity Hospital Population: Women attending the gestational diabetes outpatients’ department in CUMH. Methods: This is a retrospective cross-sectional study. The participants were divided into 2 groups: those with ALTs within the ALT N range and those with elevated but with no other documented diagnosis of liver disease that may be a cause for their elevated ALT level. Primary and secondary measure outcomes: a) To quantify the number of participants with an elevated ALT and to compare them to a group of participants with normal ALT, b) To investigate if there is an association between elevated ALT and BMI and c) To compare the two groups in terms premature birth, macrosomia, induction of labour, operative delivery and neonatal ICU admission. Results: 24.7% of women with GDM had elevated ALT. 23.9% of the entire group had elevated ALT and no diagnosis of liver disease. When this group was compared to the group with ALT N, there was a statistically significant association between elevated ALT and both elevated BMI and premature delivery. Conclusions: In this cohort there is an association between GDM and increased ALT. There is also an association between elevated ALT and increased BMI and premature. These groups should be treated as high risk pregnancies.

Solitary angiokeratoma is reported to be distinguishable from intracorneal hemorrhage. Dermoscopy shows a whitish veil in solitary angiokeratoma and a homogeneous or globular lesion in intracorneal hemorrhage. However, we encountered a case of solitary angiokeratoma that was indistinguishable from intracorneal hemorrhage by dermoscopy. Dermatologists need to recognize this dermoscopic pitfall.

In this paper, we give an elementary counterexample to show that the global $L^3$ Schr\“{o}dinger maximal estimate \begin{align*} \big\Vert \sup_{0<{\vert t \vert}\leq 1} \vert e^{it\Delta}f \vert \big\Vert_{L^3(\mathbb{R}^2)} \leq C \Vert f \Vert_{H^{s}(\mathbb{R}^2)},\;\;\forall \,f\in H^{s}(\mathbb{R}^2) \end{align*} fails if $s< \frac{1}{3}$. The argument also adapts to the case of 2D fractional Schr\”{o}dinger operators, and does not rely on any facts from number theory.

Background. Children with a brain tumor are at risk of developing sleep problems. It remains unclear whether these problems arise at an early or later stage, and insights can facilitate timely interventions. The aim of this study is to examine sleep problems and contributing factors shortly after diagnosis. Methods. Children 6-16 years with a newly diagnosed (≤3 months) primary brain tumor were recruited for a prospective study. Sleep was measured using actigraphy and questionnaires (PROMIS Sleep Disturbance and Sleep Related Impairment, self- and parent-reports). Prevalence of clinical sleep problems were established using PROMIS cut-off scores. Mean PROMIS scores, prevalence of sleep problems and actigraphic outcomes were compared to norms (t-test, chi-square, linear regression). Demographic and medical risk factors were explored with multivariable linear regression models. Results. Sixty-nine children (68% male, mean age 11.6±2.8 years, 53±28 days after diagnosis) participated. Parents reported more sleep disturbances (mean T=53.7, P<.01) compared to norms. Rates of self- and parent-reported severe sleep disturbances were elevated (11% versus 5% in norms, P<.04). Parents also reported higher rates of moderate sleep disturbance (31%) and sleep related impairment (42%) than norms (25%, P<.03). Actigraphic outcomes did not differ from norms. Only shorter time since diagnosis was identified as independent risk factor (self-reported sleep disturbances, B=-.11, 95%CI -0.19;-0.03). Conclusions. Sleep problems are more frequently reported by children and parents shortly after pediatric brain tumor diagnosis, compared to healthy controls. Attention for sleep around brain tumor diagnosis is important, as sleep is vital for recovery and health-related quality of life.

Understanding and predicting novel diseases has become very important owing to the huge global health burden. ‎Organiz‎ing and studying mathematical models ‎performs‎ an essential role in predicting the behavior of the ‎disease. ‎In this paper, a new stochastic Susceptible-Infected-Recovered-Death (SIRD) model for spreading epidemic disease is investigated. First, the deterministic SIRD model is considered, and then, by allowing randomness in the recovery and death rates that are not deterministic, the system of nonlinear stochastic differential equations is derived. For the suggested model, the existence and uniqueness of a positive global solution are demonstrated. The parameter estimation is done with the conditional least square estimator for deterministic models and the maximum likelihood estimator for stochastic ones. After that, we investigate a nonadditive state-space model for spreading epidemic disease by considering infected as the hidden process variable. The problem of the hidden process variable from noisy observations is filtered, predicted, and smoothed using a recursive Bayesian technique. For estimating the hidden number of infected variables, closed-form solutions are obtained. Finally, numerical simulations with both simulated and real data are performed to demonstrate the efficiency and accuracy of the current work.

The control of porcine reproductive and respiratory syndrome virus (PRRSV) hinges on monitoring and surveillance. The objective of this study was to assess PRRSV RNA detection by RT-PCR in tongue tips from dead suckling piglets compared to serum samples, processing fluids, and family oral fluids. Tongue tips and serum samples were collected from three PRRSV-positive breeding herd farms (farms A, B, and C) of three different age groups: newborns (<24h), processing (2 to 7 days of age), and weaning (18 to 22 days of age). Additionally, processing fluids and family oral fluids were collected from 2-7 days of age and weaning age respectively. In farms A and B, PRRSV RNA was detected in tongue tips from all age groups (100% and 95%, respectively). In addition, PRRSV RNA was detected in pooled serum samples (42% and 27%), processing fluids (100% and 50%), and family oral fluids (11% and 22%). Interestingly, the average Ct value from tongue tips was numerically lower than the average Ct value from serum samples in the newborn age. In farm C, PRRSV RNA was only detected in serum samples (60%) and family oral fluids (43%), both from the weaning age. Further, no PRRSV RNA was detected in tongue tips when pooled serum samples from the same age group tested PRRSV RNA-negative. Taken together, these results demonstrate the potential value of tongue tips for PRRSV monitoring and surveillance.

A coronavirus disease pandemic caused by the novel severe acute respiratory syndrome virus-2 or nCoV-2 has escalated to a global health emergency. In search of prospective therapeutics against the virus from the microbial treasure trove, three classes of cyclic lipopeptides produced by the bacterial genus Bacillus, namely Surfactins, Fengycins, and Iturins, were chosen as exploitative targets against the main viral protease, 3CLPro, in turn, responsible for the ordered transcription and replication of the virus. On performing molecular docking analysis using AutoDock Vina, all the annotated lipopeptides showed promising binding stability, ranging from -6.1 to -7.4 kcal/mol, compared with the control inhibitor Darunavir (-7.2 kcal/mol). The lowest binding energy was observed for Fengycin 35518574 whereas the highest was for Surfactin B, but due to the richness in forming effective interactions with the target, Surfactin C was adjudged the most potent among all others. Molecular dynamics simulation analysis using iMODs server strengthened our claim that the 3CLPro-Surfactin C complex was stable, based on Deformability, Bfactor, Eigenvalue, Covariance, and Elastic network modeling. All the lipopeptides were found to form multiple hydrogen-bonded and hydrophobic interactions with the enzyme, in-silico, due to the exposed polyhydroxyl moieties and prenyl groups in their peptide structures. As most of these lipopeptides are non-toxic to human cells, the results of this study emphasize the need for research using these wonder molecules and their derivatives as pharmaceuticals in combating notorious viruses like nCoV-2.  

A 59-year-old Afro-American woman presented with a gradual loss of hair and scalp pruritus for the last year. The complementary tests revealed a scalp thickness of 10,1mm and a punch biopsy confirmed the diagnosis of a lipedematous alopecia. This, together with lipedematous scalp, are uncommon clinicopathologic entities of unknow etiology.

Community dynamics are governed by two opposed processes: species sorting, which produces deterministic dynamics leading to an equilibrium state, and ecological drift, which produces stochastic dynamics. Despite a great deal of theoretical and empirical work aiming to demonstrate the predominance of one or the other of these processes, the importance of drift in structuring communities and maintaining species diversity remains contested. Here we present the results of a basic community dynamics experiment using floating aquatic plants, designed to measure the relative contributions of species sorting, ecological drift to community change over about a dozen generations. We found that species sorting became overwhelmingly dominant as the experiment progressed, and directed communities towards a stable equilibrium state maintained by negative frequency-dependent selection. The dynamics of any particular species depended on how far its initial frequency was from its equilibrium frequency, however, and consequently the balance of sorting and drift varied among species.

Humans have translocated thousands of species, either intentionally or not, from their native ranges to non-native ones, with many established (naturalized) and some now invasive. We report here a global database on the distributions of naturalized alien insects. Currently, 7,741 naturalized alien insect species have been reported from 222 regions, of which 47 species were reported over all six continents, 103 species over five continents, and 208 species over four continents. Naturalized alien insects are taxonomically diverse in all six continents, predominantly occurring in agroecosystems, as well as forests and grasslands. North America has accumulated the greatest number of naturalized alien insect species, while South America has the lowest number. Asia donated the greatest number of its native insect species to other continents, especially to North America and Europe. The global patterns of naturalized alien insects are correlated with transcontinental trade and the number of local scientists who study insect invasions. Most naturalized alien insects have been introduced to multiple continents, further facilitating the expansion of introduced populations through bridgehead effects. Understanding the global exchange and accumulation of alien insects helps the development of an early warning and monitoring system for insect invasions.

Aim: To summarise the effectiveness of organisational interventions on appropriate opioid use for non-cancer pain upon hospital discharge. Methods: A systematic search was conducted on six electronic databases by two independent reviewers. We included original research articles reporting on quantitative outcomes of organisational interventions targeting appropriate opioid use on hospital discharge. Quality assessment was performed by two independent reviewers. The protocol for this review was prospectively registered on PROSPERO (ID: CRD42020156104). Results: Out of 173 full texts assessed for eligibility, 43 were included in this review. The majority of studies had a moderate to serious risk of bias (33 out of 43). Most of the studies implemented a multifaceted organisational intervention (16 studies). Other interventions included guideline implementation, prescriber education and default opioid prescribing quantity changes in electronic medical records. Multiple studies found that the dissemination of patient-specific and procedure-specific guidelines reduced the quantity of opioids prescribed by 44-57%. Prescriber education provided with feedback was implemented in four studies and resulted in a 33-44% decrease in prescribing rates. Lowering the default quantities in the electronic medical records produced a 40% decrease in opioids prescribed in one study. Conclusion: Guideline implementation, prescriber education and default opioid prescribing quantity changes all appear effective in improving the appropriate use of opioids on hospital discharge. However, the extent of reduction of opioid prescribing upon hospital discharge after the implementation of multifaceted intervention strategies appears similar to that of simpler interventions which require fewer resources.

Growing body of evidence supporting the use ofBivalirudin as alternative anticoagulation during extracorporeal membrane oxygenation.

The MitraClip technique has been increasingly used for correction of mitral valve regurgitation in patients in whom surgical mitral repair is considered contraindicated or very risky, but off label use occurs often. Failure of the procedure, translated into moderate to severe rates of residual or recurrent mitral regurgitation, is observed in up to one-third of the patients, and surgery has been used to correct it in a number of cases, in what can be called an “operation for the inoperable”. That is precisely the subtitle of a paper published in this issue of the JOCS by Gerfen and colleagues, who analyse their institutional experience with a series of 17 patients. In this Editorial, I comment on this series and the possible reasons for failure of the MitraClip, and on the indications for reintervention and its constraints, which I hope can contribute to the discussion about “further exploration and refinement of patient selection criteria and identify predictors for MitraClip failure”, as the authors suggest.

The dominant method for generating Chinese hamster ovary (CHO) cell lines that produce high titers of biotherapeutic proteins utilizes selectable markers such as dihydrofolate reductase (Dhfr) or glutamine synthetase (Gs), alongside inhibitory compounds like methotrexate (MTX) or methionine sulfoximine (MSX), respectively. Recent work has shown the importance of asparaginase (Aspg) for growth in media lacking glutamine–the selection medium for Gs-based selection systems. We generated a Gs/Aspg double knockout CHO cell line and evaluated its utility as a novel dual selectable system via co-transfection of Gs-Enbrel and Aspg-Enbrel plasmids. Using the same selection conditions as the standard Gs system, the resulting cells from the Gs/Aspg dual selection showed substantially improved specific productivity and titer compared to the standard Gs selection method, however, with reduced growth rate and viability. Following adaptation in selection medium, the cells improved viability and growth while still achieving ~5-fold higher specific productivity and ~3-fold higher titer than Gs selection alone. We anticipate that with further optimization of culture medium and selection conditions this approach would serve as an effective addition to workflows for the industrial production of recombinant biotherapeutics.

Background Data on the postoperative outcomes for patients with infective endocarditis complicated by an aortic root abscess is sparse due to the condition’s low incidence and high mortality rates. This systematic review and meta-analysis aims to evaluate existing data on the impact of aortic root abscesses (ARA) on the postoperative outcomes of surgically managed infective endocarditis (IE) and to inform optimal surgical approach. Methods The online databases MEDLINE, EMBASE and Cochrane library were searched from 1990 to 2022 for studies comparing ARA with NARA (no ARA) in infective endocarditis. Data was extracted by two independent investigators and aggregated in a random-effects model (Review Manager version 5.3). Risk of bias was assessed using an adapted version of the Newcastle-Ottawa scale. Results Six clinical studies were included in the meta-analysis (n = 1982). The ARA group was associated with an increased risk of in-hospital mortality (OR = 1.74 96% CI 1.18-2.56) and late mortality (HR = 1.27 95% CI 1.03-1.58). The reoperation meta-analysis was complicated by high rates of heterogeneity (I 2 = 59%) and found no significant differences in reoperation between group ARA and NARA (no ARA) (HR = 1.48; 95% CI 0.92-2.40). Post-hoc scatter graph showed a strong linear relationship (r=0.998), suggesting hospitals with higher rates of aortic root replacement (ARR) achieve lower rates of reoperation for ARA patients compared with PR. Conclusions The presence of an ARA in aortic valve endocarditis is associated with elevated early and late mortality despite modern standards of care. Additionally, ARR should be considered to have a favourable postoperative profile for use in this context.

Objective: To evaluate the functional capacity, pulmonary function and quality of life of children and adolescents with sickle cell anemia (SCA) and to test the reproducibility of functional capacity tests in this population. Method: Cross-sectional study with  volunteers with SCA genotype Hb-SS (SCAG), aged 6 to 18 years matched in age and  gender to the control group (CG). Spirometry, 5-repetition sit-to-stand test (5STS-test),  modified shuttle walk test (MSWT), and Pediatric Quality of Life Questionnaire (PedsQL) were performed. The reproducibility of 5STS-test and MSWT was evaluated:   Results: 48 volunteers of SCAG and 48 of CG were evaluated. Pulmonary function of SCAG (FVC: 92 ± 15% pred.; FEV 1 /FVC: 84 ± 8% pred.) was worse than the CG (104 ± 15% pred.; FEV 1 /FVC: 90 ± 6% pred.) p < 0.05. SCAG had worse functional capacity registered by distance walked: 576m (515-672m) and 5STS-test: 8 seconds (7.4-8.9seconds) compared to the CG who showed distance walked: 1010m (887- 1219m) and 5STS-test: 7 seconds (7.0-8.1seconds), p < 0.001. SCAG had worse quality compared to CG, p < 0.05. The reproducibility was good of MSWT (ICC 0.99 (0.98-0.99 IC-95%)) and 5STS-test (ICC 0.80 (0.69 – 0.88), p < 0.001 . Conclusion: Children and adolescents with sickle cell anemia showed worse capacity to walk or run, and to perform sit-to-stand test. Additionally, they have poor quality of life when compared with their control peers. The MSWT and 5STS-test showed reproducible to be applied in pediatric individual with SCA.