A procedure for maximizing the coefficient of generalizability under the constraint of limited resources is presented. The procedure uses optimization techniques that offer an investigator or test constructor the possibility of employing practical constraints. The procedure is illustrated for the two-facet random-model crossed design.

A new method for determining the minimum number of observations per subject needed to achieve a specific generalizability coefficient is presented. This method, which consists of a branch-and-bound algorithm, allows for the employment of constraints specified by the investigator.

To investigate the potential application of replacing a proportion of a perennial ryegrass (PRG) silage diet with press cake on productivity and enteric methane (CH4) emissions in late lactation and non-lactating spring-calving dairy cows, a study was undertaken in which control cows (n = 21) were offered PRG silage, while treatment cows (n = 21) were offered a diet consisting of 60% PRG press cake and 40% of the same PRG silage. Although treatment cows had higher group average dry matter intakes (DMI) and produced more enteric CH4, carbon dioxide (CO2), milk solids, protein, fat- and protein-corrected milk yield (FPCM) in late lactation, the magnitude of the difference between treatment and control cows varied from week to week (P < 0.050). When enteric CH4 per kg of milk yield, milk solids and FPCM were considered, there was no significant difference between treatment and control. Absolute enteric CH4 was higher for cows fed press cake during the non-lactating period but this tended to vary from week to week. Similarly, CO2 (P < 0.001) and hydrogen (H2; P = 0.023) differed from week to week for cows offered press cake, and cows offered PRG silage in the non-lactating period. Although there was no significant effect of diet on body weight (BW) and body condition score (BCS), when enteric CH4 was expressed on a per kg BW basis, cows offered press cake tended to produce more enteric CH4 in both late lactation and during the dry period.

Reducing antimicrobial use (AMU) in livestock may be one of the keys to limit the emergence of antimicrobial resistance (AMR) in bacterial populations, including zoonotic pathogens. This study assessed the temporal association between AMU in livestock and AMR among Campylobacter isolates from human infections in the Netherlands between 2004 – 2020. Moreover, the associations between AMU and AMR in livestock and between AMR in livestock and AMR in human isolates were assessed. AMU and AMR data per antimicrobial class (tetracyclines, macrolides and fluoroquinolones) for Campylobacter jejuni and Campylobacter coli from poultry, cattle, and human patients were retrieved from national surveillance programs. Associations were assessed using logistic regression and the Spearman correlation test. Overall, there was an increasing trend in AMR among human C. jejuni/coli isolates during the study period, which contrasted with a decreasing trend in livestock AMU. In addition, stable trends in AMR in broilers were observed. No significant associations were observed between AMU and AMR in domestically produced broilers. Moderate to strong positive correlations were found between the yearly prevalence of AMR in broiler and human isolates. Reducing AMU in Dutch livestock alone may therefore not be sufficient to tackle the growing problem of AMR in Campylobacter among human cases in the Netherlands. More insight is needed regarding the population genetics and the evolutionary processes involved in resistance and fitness among Campylobacter.

Substantial progress has been made in the standardization of nomenclature for paediatric and congenital cardiac care. In 1936, Maude Abbott published her Atlas of Congenital Cardiac Disease, which was the first formal attempt to classify congenital heart disease. The International Paediatric and Congenital Cardiac Code (IPCCC) is now utilized worldwide and has most recently become the paediatric and congenital cardiac component of the Eleventh Revision of the International Classification of Diseases (ICD-11). The most recent publication of the IPCCC was in 2017. This manuscript provides an updated 2021 version of the IPCCC.

The International Society for Nomenclature of Paediatric and Congenital Heart Disease (ISNPCHD), in collaboration with the World Health Organization (WHO), developed the paediatric and congenital cardiac nomenclature that is now within the eleventh version of the International Classification of Diseases (ICD-11). This unification of IPCCC and ICD-11 is the IPCCC ICD-11 Nomenclature and is the first time that the clinical nomenclature for paediatric and congenital cardiac care and the administrative nomenclature for paediatric and congenital cardiac care are harmonized. The resultant congenital cardiac component of ICD-11 was increased from 29 congenital cardiac codes in ICD-9 and 73 congenital cardiac codes in ICD-10 to 318 codes submitted by ISNPCHD through 2018 for incorporation into ICD-11. After these 318 terms were incorporated into ICD-11 in 2018, the WHO ICD-11 team added an additional 49 terms, some of which are acceptable legacy terms from ICD-10, while others provide greater granularity than the ISNPCHD thought was originally acceptable. Thus, the total number of paediatric and congenital cardiac terms in ICD-11 is 367. In this manuscript, we describe and review the terminology, hierarchy, and definitions of the IPCCC ICD-11 Nomenclature. This article, therefore, presents a global system of nomenclature for paediatric and congenital cardiac care that unifies clinical and administrative nomenclature.

The members of ISNPCHD realize that the nomenclature published in this manuscript will continue to evolve. The version of the IPCCC that was published in 2017 has evolved and changed, and it is now replaced by this 2021 version. In the future, ISNPCHD will again publish updated versions of IPCCC, as IPCCC continues to evolve.

Within the vigilance regulation model the hyperactivity and sensation seeking observed in overtired children, ADHD and mania are interpreted as an autoregulatory attempt to stabilize vigilance (central nervous arousal) by increasing external stimulation. Correspondingly the withdrawal and sensation avoidance in major depression is interpreted as a reaction to a state of tonically high vigilance (1, 2). Using an EEG-based algorithm to classify automatically short EEG-segments into different vigilance stages as observed during the transition from active wakefulness to drowsiness and sleep onset (VIGALL), both patients with ADHD and mania show an unstable vigilance regulation with rapid drops to lower vigilance stages under quiet rest. The contrary was found in unmedicated patients with major depression (2). Studies will be presented supporting the validity of VIGALL (simulataneous EEG-fMRI and EEG/FDG-PET studies, as well as the neurophysiological, clinical and predictive validity of the vigilance regulation model of affective disorders. Among the far reaching consequences of the vigilance model is the question whether psychostimulants have similar beneficial effects in mania as observed in ADHD (3), an aspect which is presently studied in an international, randomized controlled trial (4).

Minor depression is diagnosed when a patient suffers from two to four depressive symptoms for at least two weeks. Though minor depression is a widespread phenomenon, its pathophysiology has hardly been studied. To get a first insight into the pathophysiological mechanisms underlying this disorder we assessed serum levels of biomarkers for plasticity, glial and neuronal function: brain-derived neurotrophic factor (BDNF), S100B and neuron specific enolase (NSE). Twenty-seven subjects with minor depressive episode and 82 healthy subjects over 60 years of age were selected from the database of the Leipzig population-based study of civilization diseases (LIFE). Serum levels of BDNF, S100B and NSE were compared between groups, and correlated with age, body-mass index, and degree of white matter hyperintensities (score on Fazekas scale). S100B was significantly increased in males with minor depression in comparison to healthy males, whereas other biomarkers did not differ between groups (P = 0.10–0.66). NSE correlated with Fazekas score in patients with minor depression (rs = 0.436, P = 0.048) and in the whole sample (rs = 0.252, P = 0.019). S100B correlated with body mass index (rs = 0.246, P = 0.031) and with age in healthy subjects (rs = 0.345, P = 0.002). Increased S100B in males with minor depression, without alterations in BDNF and NSE, supports the glial hypothesis of depression. Correlation between white matter hyperintensities and NSE underscores the vascular hypothesis of late life depression.

We present results on the global and local characterisation of heat transport in homogeneous bubbly flow. Experimental measurements were performed with and without the injection of ${\sim}2.5~\text{mm}$ diameter bubbles (corresponding to bubble Reynolds number $Re_{b}\approx 600$ ) in a rectangular water column heated from one side and cooled from the other. The gas volume fraction $\unicode[STIX]{x1D6FC}$ was varied in the range 0 %–5 %, and the Rayleigh number $Ra_{H}$ in the range $4.0\times 10^{9}{-}1.2\times 10^{11}$ . We find that the global heat transfer is enhanced up to 20 times due to bubble injection. Interestingly, for bubbly flow, for our lowest concentration $\unicode[STIX]{x1D6FC}=0.5\,\%$ onwards, the Nusselt number $\overline{Nu}$ is nearly independent of $Ra_{H}$ , and depends solely on the gas volume fraction $\unicode[STIX]{x1D6FC}$ . We observe the scaling $\overline{Nu}\,\propto \,\unicode[STIX]{x1D6FC}^{0.45}$ , which is suggestive of a diffusive transport mechanism, as found by Alméras et al. (J. Fluid Mech., vol. 776, 2015, pp. 458–474). Through local temperature measurements, we show that the bubbles induce a huge increase in the strength of liquid temperature fluctuations, e.g. by a factor of 200 for $\unicode[STIX]{x1D6FC}=0.9\,\%$ . Further, we compare the power spectra of the temperature fluctuations for the single- and two-phase cases. In the single-phase cases, most of the spectral power of the temperature fluctuations is concentrated in the large-scale rolls/motions. However, with the injection of bubbles, we observe intense fluctuations over a wide range of scales, extending up to very high frequencies. Thus, while in the single-phase flow the thermal boundary layers control the heat transport, once the bubbles are injected, the bubble-induced liquid agitation governs the process from a very small bubble concentration onwards. Our findings demonstrate that the mixing induced by high Reynolds number bubbles ($Re_{b}\approx 600$ ) offers a powerful mechanism for heat transport enhancement in natural convection systems.

Higher-educated people often have healthier diets, but it is unclear whether specific dietary patterns exist within educational groups. We therefore aimed to derive dietary patterns in the total population and by educational level and to investigate whether these patterns differed in their composition and associations with the incidence of fatal and non-fatal CHD and stroke. Patterns were derived using principal components analysis in 36 418 participants of the European Prospective Investigation into Cancer and Nutrition-Netherlands cohort. Self-reported educational level was used to create three educational groups. Dietary intake was estimated using a validated semi-quantitative FFQ. Hazard ratios were estimated using Cox Proportional Hazard analysis after a mean follow-up of 16 years. In the three educational groups, similar ‘Western’, ‘prudent’ and ‘traditional’ patterns were derived as in the total population. However, with higher educational level a lower population-derived score for the ‘Western’ and ‘traditional’ patterns and a higher score on the ‘prudent’ pattern were observed. These differences in distribution of the factor scores illustrate the association between education and food consumption. After adjustments, no differences in associations between population-derived dietary patterns and the incidence of CHD or stroke were found between the educational groups (Pinteraction between 0·21 and 0·98). In conclusion, although in general population and educational groups-derived dietary patterns did not differ, small differences between educational groups existed in the consumption of food groups in participants considered adherent to the population-derived patterns (Q4). This did not result in different associations with incident CHD or stroke between educational groups.

Pb-based organometal halide perovskite solar cells have passed the threshold of 20 % power conversion efficiency (PCE). However, the main issues hampering commercialization are toxic Pb contained in these cells and their instability in ambient air. Therefore, great attention is devoted to replace Pb by Sn or Bi, which are less harmful and - in the case of Bi - also expected to yield enhanced stability. In literature, the most efficient hybrid organic-inorganic methylammonium bismuth iodide (MBI) perovskite solar cells reach PCE up to 0.2 %. In this work, we present spin-coated MBI perovskite solar cells and highlight the impact of the concentration of the perovskite solution on the layer morphology and photovoltaic (PV) characteristics. The solar cells exhibit open-circuit voltages of 0.73 V, which is the highest value published for this type of solar cell. The PCE increases from 0.004 % directly after processing to 0.17 % after 48 h of storage in air. 300 h after exposure to air, the cells still yield 56 % of their peak PCE and 84 % of their maximum open-circuit voltage.

Human mesenchymal stem cells were reseeded in decellularized human bone subject to a controlled mechanical loading to create a bone-on-chip that was cultured for over 26 months. The cell morphology and their secretome were characterized using immunohistochemistry and in situ immunofluorescence under confocal microscopy. The presence of stem cell derived osteocytes was confirmed at 547 days. Different cell populations were identified. Some cells were connected by long processes and formed a network. Comparison of the MSCs in vitro reorganization and calcium response to in situ mechanical stimulation were compared to MLOY4 cells reseeded on human bone. The bone-on-chip produced an ECM of which the strength was nearly a quarter of native bone after 109 days and that contained calcium minerals at 39 days and type I collagen at 256 days. The cytoplasmic calcium concentration variations seemed to adapt to the expected in vivo mechanical load at the successive stages of cell differentiation in agreement with studies using fluid shear flow stimulation. Some degree of bone-like formation over a long period of time with the formation of a newly formed matrix was observed.

We have investigated organic light emitting diode (OLED) backside contacting for the enhancement of luminance uniformity as a superior alternative to gridlines. In this approach, the low-conductivity OLED anode is supported by a high-conductivity auxiliary electrode and vertically contacted through via holes. Electrical simulations of large-area OLEDs have predicted that this method allows comparable luminance uniformity while sacrificing significantly less active area compared to the common gridline approach.

The method for fabricating backside contacts is comprised of five steps: (1) Thin-film encapsulation of the OLED, (2) Patterning of the OLED surface with lithography (resist mask defining via hole positions), (3) Via hole formation to the bottom anode by a plasma etching process, (4) Organic residues removal and sidewall insulation. (5) Contacting of the anode with a high-conductivity auxiliary electrode.

Backside-contacted OLEDs processed by organic vapor phase deposition show high luminance uniformity. Scanning electron microscopy pictures and electrical breakthrough measurements confirm efficient sidewall insulation.

Recently, organometal halide perovskite solar cells have passed the threshold of 20 % power conversion efficiency (PCE). While such PCE values of perovskite solar cells are already competitive to those of other photovoltaic technologies, processing of large-area devices is still a challenge. Most of the devices reported in literature are prepared by small-scale solution-based processing techniques (e.g. spin-coating). Perovskite solar cells processed by vacuum thermal evaporation (VTE), which show uniform layers and achieve higher PCE and better reproducibility, have also been presented. Regarding the co-evaporation of the perovskite constituents, this technology suffers from large differences in the thermodynamic characteristics of the two species. While the organic components evaporate instantaneously at room temperature at pressures in the range of 10−6 hPa, significantly higher temperatures are needed for reasonable deposition rates of the metal halide compound. In addition, hybrid vapor phase deposition techniques have been developed employing a carrier gas to deposit the organic compound on the previously solution-processed metal halide compound. Generally, vapor phase processes have proven to be a desirable choice for industrial large-area production. In this work, we present a setup for the direct chemical vapor phase deposition (CVD) of methylammonium lead iodide (MAPbI3) employing nitrogen as carrier gas. X-ray diffraction (XRD) and scanning electron microscopy (SEM) measurements are carried out to investigate the crystal quality and structural properties of the resulting perovskite. By optimizing the deposition parameters, we have produced perovskite films with a deposition rate of 30 nm/h which are comparable to those fabricated by solution processing. Furthermore, the developed CVD process can be easily scaled up to higher deposition rates and larger substrates sizes, thus rendering this technique a promising candidate for manufacturing large-area devices. Moreover, CVD of perovskite solar cells can overcome most of the limitations of liquid processing, e.g. the need for appropriate and orthogonal solvents.

Stroke is a leading cause of morbidity and mortality in the US, with secondary damage following the initial insult contributing significantly to overall poor outcome. Prior investigations have shown that the metabolism of certain polyamines such as spermine, spermidine, and putrescine are elevated in ischemic parenchyma, resulting in an increase in their metabolite concentration. Polyamine metabolites tend to be cytotoxic, leading to neuronal injury in the penumbra following stroke and expansion of the area of infarcted tissue. Although the precise mechanism is unclear, the presence of reactive aldehydes produced through polyamine metabolism, such as 3-aminopropanal and acrolein, have been shown to correlate with the incidence of cerebral vasospasm, disruption of oxidative metabolism and mitochondrial functioning, and disturbance of cellular calcium ion channels. Regulation of the polyamine metabolic pathway, therefore, may have the potential to limit injury following cerebral ischemia. To this end, we review this pathway in detail with an emphasis on clinical applicability.