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Grazing and ruminating are the most important behaviours for ruminants, as they spend most of their daily time budget performing these. Continuous surveillance of eating behaviour is an important means for monitoring ruminant health, productivity and welfare. However, surveillance performed by human operators is prone to human variance, time-consuming and costly, especially on animals kept at pasture or free-ranging. The use of sensors to automatically acquire data, and software to classify and identify behaviours, offers significant potential in addressing such issues. In this work, data collected from sheep by means of an accelerometer/gyroscope sensor attached to the ear and collar, sampled at 16 Hz, were used to develop classifiers for grazing and ruminating behaviour using various machine learning algorithms: random forest (RF), support vector machine (SVM), k nearest neighbour (kNN) and adaptive boosting (Adaboost). Multiple features extracted from the signals were ranked on their importance for classification. Several performance indicators were considered when comparing classifiers as a function of algorithm used, sensor localisation and number of used features. Random forest yielded the highest overall accuracies: 92% for collar and 91% for ear. Gyroscope-based features were shown to have the greatest relative importance for eating behaviours. The optimum number of feature characteristics to be incorporated into the model was 39, from both ear and collar data. The findings suggest that one can successfully classify eating behaviours in sheep with very high accuracy; this could be used to develop a device for automatic monitoring of feed intake in the sheep sector to monitor health and welfare.

Our cluster analysis of the Cancer Genome Atlas for co-expression of HSP27 and CRYAB in breast cancer patients identified three patient groups based on their expression level combination (high HSP27 + low CRYAB; low HSP27 + high CRYAB; similar HSP27 + CRYAB). Our analyses also suggest that there is a statistically significant inverse relationship between HSP27 and CRYAB and known clinicopathological markers in breast cancer. Screening an unbiased 248 breast cancer patient tissue microarray (TMA) for the protein expression of HSP27 and phosphorylated HSP27 (HSP27-82pS) with CRYAB also identified three patient groups based on HSP27 and CRYAB expression levels. TMA24 also had recorded clinical-pathological parameters, such as ER and PR receptor status, patient survival, and TP53 mutation status. High HSP27 protein levels were significant with ER and PR expression. HSP27-82pS associated with the best patient survival (Log Rank test). High CRYAB expression in combination with wild-type TP53 was significant for patient survival, but a different patient outcome was observed when mutant TP53 was combined with high CRYAB expression. Our data suggest that HSP27 and CRYAB have different epichaperome influences in breast cancer, but more importantly evidence the value of a cluster analysis that considers their coexpression. Our approach can deliver convergence for archival datasets as well as those from recent treatment and patient cohorts and can align HSP27 and CRYAB expression to important clinical-pathological features of breast cancer.

The most frequent genetic alterations across multiple human cancers are mutations in TP53 and the activation of the PI3K/AKT pathway, two events crucial for cancer progression. Mutations in TP53 lead to the inhibition of the tumour and metastasis suppressor TAp63 , a p53 family member. By performing a mouse-human cross species analysis between the TAp63 metastatic mammary adenocarcinoma mouse model and models of human breast cancer progression, we identified two TAp63-regulated oncogenic lncRNAs, TROLL-2 and TROLL-3 . Further, using a pan-cancer analysis of human cancers and multiple mouse models of tumour progression, we revealed that these two lncRNAs induce the activation of AKT to promote cancer progression by regulating the nuclear to cytoplasmic translocation of their effector, WDR26, via the shuttling protein NOLC1. Our data provide preclinical rationale for the implementation of these lncRNAs and WDR26 as therapeutic targets for the treatment of human tumours dependent upon mutant TP53 and/or the PI3K/AKT pathway. Mutations in TP53 and hyperactivation of the PI3K/AKT pathway are the two most frequent drivers of cancer progression across multiple human tumour types. Here, the authors identify two TAp63 regulated long non-coding RNAs, TROLL-2 and TROLL-3 , that connect these oncogenic pathways, thus promoting tumour and metastasis formation in a wide variety of cancer types.

The realization of nanophotonic optical isolators with high optical isolation even at ultralow light levels and low optical losses is an open problem. Here, we employ the link between the local polarization of strongly confined light and its direction of propagation to realize low-loss nonreciprocal transmission through a silica nanofiber at the single-photon level. The direction of the resulting optical isolator is controlled by the spin state of cold atoms. We perform our experiment in two qualitatively different regimes, i.e., with an ensemble of cold atoms where each atom is weakly coupled to the waveguide and with a single atom strongly coupled to the waveguide mode. In both cases, we observe simultaneously high isolation and high forward transmission. The isolator concept constitutes a nanoscale quantum optical analog of microwave ferrite resonance isolators, can be implemented with all kinds of optical waveguides and emitters, and might enable novel integrated optical devices for fiber-based classical and quantum networks.

Background The importance of albuminuria as opposed to proteinuria in predicting kidney outcomes in primary immunoglobulin A nephropathy (IgAN) is not well established. Methods From 2010 to 2012, 421 patients with biopsy-proven IgAN have been enrolled into the German Chronic Kidney Disease (GCKD) cohort, a prospective observational cohort study (N = 5217). Adjudicated endpoints include a composite kidney endpoint (CKE) consisting of eGFR decline >40%, eGFR <15 ml/min/1.73 m2 and initiation of kidney replacement therapy; the individual components of the CKE; and combined major adverse cardiac events (MACE), including non-fatal myocardial infarction, non-fatal stroke and all-cause mortality. The associations between the incidence of CKE and baseline factors, including demographics, laboratory values and comorbidities were analysed using the Cox proportional hazards regression model. Results The mean age of IgAN patients at baseline was 51.6 years (± 13.6) and 67% were male. The patient-reported duration of disease at baseline was 5.9 ± 8.1 years. Baseline median urine albumin:creatinine ratio (UACR) was 0.4 g/g [interquartile range (IQR) 0.1-0.8] and mean eGFR was 52.5 ± 22.4 ml/min/1.73 m2. Over a follow-up of 6.5 years, 64 (15.2%) patients experienced a >40% eGFR decline, 3 (0.7%) reached eGFR <15 ml/min/1.73 m2, 53 (12.6%) initiated kidney replacement therapy and 28% of the patients experienced the CKE. Albuminuria, with reference to <0.1 g/g, was most associated with CKE. Hazard ratios (HRs) at UACRs of 0.1-0.6 g/g, 0.6-1.4 g/g, 1.4-2.2 g/g and >2.2 g/g were 2.03 [95% confidence interval (CI) 1.02-4.05], 3.8 (95% CI 1.92-7.5), 5.64 (95% CI 2.58-12.33) and 5.02 (95% CI 2.29-11-03), respectively. Regarding MACE, the presence of diabetes [HR 2.53 (95% CI 1.11-5.78)] was the most strongly associated factor, whereas UACR and eGFR did not show significant associations. Conclusion In the GCKD IgAN subcohort, more than every fourth patient experienced a CKE event within 6.5 years. Our findings support the use of albuminuria as a surrogate to assess the risk of poor kidney outcomes.

Background Focal segmental glomerulosclerosis (FSGS) can lead to kidney failure in adults. This study examines the progression of FSGS in the German Chronic Kidney Disease (GCKD) cohort. Methods The GCKD study (N = 5217), a prospective cohort, included 159 patients with biopsy-confirmed FSGS recruited from 2010 to 2012. Baseline was defined as the first study visit. Adjudicated endpoints included a composite kidney endpoint (CKE), including an estimated glomerular filtration rate (eGFR) decrease >40%, eGFR <15 ml/min/1.73 m2 or initiation of kidney replacement therapy and combined major adverse cardiovascular events (MACE), including non-fatal myocardial infarction or stroke and all-cause mortality. Associations between baseline demographics, laboratory data, comorbidity and CKE and MACE were analysed using the Cox proportional hazards regression model. Results The mean age at baseline was 52.1 ± 13.6 years, with a disease duration of 4.72 years (quartile 1: 1; quartile 3: 6) before joining the study. The median urinary albumin:creatinine ratio (UACR) at baseline was 0.7 g/g (IQR 0.1;1.8), while mean eGFR was 55.8 ± 23 ml/min/1.73 m2. Based on clinical and pathological features, 69 (43.4%) patients were categorized as primary FSGS, 55 (34.6%) as secondary FSGS and 35 (22%) as indeterminate. Over a follow-up of 6.5 years, 44 patients reached the composite kidney endpoint and 16 individuals had at least one MACE. UACR ≥0.7 g/g was strongly associated with both the composite kidney endpoint {hazard ratio [HR] 5.27 [95% confidence interval (CI) 2.4–11.5]} and MACE [HR 3.37 (95% CI 1.05–10.82)] compared with <0.7 g/g, whereas a higher eGFR at baseline (per 10 ml/min) was protective for both endpoints [HR 0.8 (95% CI 0.68–0.95) and HR 0.63 (95% CI 0.46–0.88), respectively]. Patients with secondary FSGS experienced a greater rate of eGFR decline than patients with primary FSGS. Conclusions Lower eGFR and higher albuminuria are key risk factors for kidney disease progression and cardiovascular events in patients with FSGS.

Chronic kidney disease (CKD) is a risk factor for development and progression of heart failure (HF). CKD and HF share common risk factors, but few data exist on the prevalence, signs and symptoms as well as correlates of HF in populations with CKD of moderate severity. We therefore aimed to examine the prevalence and correlates of HF in the German Chronic Kidney Disease (GCKD) study, a large observational prospective study. We analyzed data from 5,015 GCKD patients aged 18-74 years with an estimated glomerular filtration rate (eGFR) of <60 ml/min/1.73m² or with an eGFR ≥60 and overt proteinuria (>500 mg/d). We evaluated a definition of HF based on the Gothenburg score, a clinical HF score used in epidemiological studies (Gothenburg HF), and self-reported HF. Factors associated with HF were identified using multivariable adjusted logistic regression. The prevalence of Gothenburg HF was 43% (ranging from 24% in those with eGFR >90 to 59% in those with eGFR<30 ml/min/1.73m2). The corresponding estimate for self-reported HF was 18% (range 5%-24%). Lower eGFR was significantly and independently associated with the Gothenburg definition of HF (p-trend <0.001). Additional significantly associated correlates included older age, female gender, higher BMI, hypertension, diabetes mellitus, valvular heart disease, anemia, sleep apnea, and lower educational status. The burden of self-reported and Gothenburg HF among patients with CKD is high. The proportion of patients who meet the criteria for Gothenburg HF in a European cohort of patients with moderate CKD is more than twice as high as the prevalence of self-reported HF. However, because of the shared signs, symptoms and medications of HF and CKD, the Gothenburg score cannot be used to reliably define HF in CKD patients. Our results emphasize the need for early screening for HF in patients with CKD.

Sharing data from clinical studies can accelerate scientific progress, improve transparency, and increase the potential for innovation and collaboration. However, privacy concerns remain a barrier to data sharing. Certain concerns, such as reidentification risk, can be addressed through the application of anonymization algorithms, whereby data are altered so that it is no longer reasonably related to a person. Yet, such alterations have the potential to influence the data set's statistical properties, such that the privacy-utility trade-off must be considered. This has been studied in theory, but evidence based on real-world individual-level clinical data is rare, and anonymization has not broadly been adopted in clinical practice. The goal of this study is to contribute to a better understanding of anonymization in the real world by comprehensively evaluating the privacy-utility trade-off of differently anonymized data using data and scientific results from the German Chronic Kidney Disease (GCKD) study. The GCKD data set extracted for this study consists of 5217 records and 70 variables. A 2-step procedure was followed to determine which variables constituted reidentification risks. To capture a large portion of the risk-utility space, we decided on risk thresholds ranging from 0.02 to 1. The data were then transformed via generalization and suppression, and the anonymization process was varied using a generic and a use case-specific configuration. To assess the utility of the anonymized GCKD data, general-purpose metrics (ie, data granularity and entropy), as well as use case-specific metrics (ie, reproducibility), were applied. Reproducibility was assessed by measuring the overlap of the 95% CI lengths between anonymized and original results. Reproducibility measured by 95% CI overlap was higher than utility obtained from general-purpose metrics. For example, granularity varied between 68.2% and 87.6%, and entropy varied between 25.5% and 46.2%, whereas the average 95% CI overlap was above 90% for all risk thresholds applied. A nonoverlapping 95% CI was detected in 6 estimates across all analyses, but the overwhelming majority of estimates exhibited an overlap over 50%. The use case-specific configuration outperformed the generic one in terms of actual utility (ie, reproducibility) at the same level of privacy. Our results illustrate the challenges that anonymization faces when aiming to support multiple likely and possibly competing uses, while use case-specific anonymization can provide greater utility. This aspect should be taken into account when evaluating the associated costs of anonymized data and attempting to maintain sufficiently high levels of privacy for anonymized data. German Clinical Trials Register DRKS00003971; https://drks.de/search/en/trial/DRKS00003971. RR2-10.1093/ndt/gfr456.

Background Chronic kidney disease (CKD) is highly connected to inflammation and oxidative stress. Both favour the development of cancer in CKD patients. Serum apolipoprotein A-IV (apoA-IV) concentrations are influenced by kidney function and are an early marker of kidney impairment. Besides others, it has antioxidant and anti-inflammatory properties. Proteomic studies and small case–control studies identified low apoA-IV as a biomarker for various forms of cancer; however, prospective studies are lacking. We therefore investigated whether serum apoA-IV is associated with cancer in the German Chronic Kidney Disease (GCKD) study. Methods These analyses include 5039 Caucasian patients from the prospective GCKD cohort study followed for 6.5 years. Main inclusion criteria were an eGFR of 30–60 mL/min/1.73m 2 or an eGFR > 60 mL/min/1.73m 2 in the presence of overt proteinuria. Results Mean apoA-IV concentrations of the entire cohort were 28.9 ± 9.8 mg/dL (median 27.6 mg/dL). 615 patients had a history of cancer before the enrolment into the study. ApoA-IV concentrations above the median were associated with a lower odds for a history of cancer (OR = 0.79, p  = 0.02 when adjusted age, sex, smoking, diabetes, BMI, albuminuria, statin intake, and eGFR creatinine ). During follow-up 368 patients developed an incident cancer event and those with apoA-IV above the median had a lower risk (HR = 0.72, 95%CI 0.57–0.90, P  = 0.004). Finally, 62 patients died from such an incident cancer event and each 10 mg/dL higher apoA-IV concentrations were associated with a lower risk for fatal cancer (HR = 0.62, 95%CI 0.44–0.88, P  = 0.007). Conclusions Our data indicate an association of high apoA-IV concentrations with reduced frequencies of a history of cancer as well as incident fatal and non-fatal cancer events in a large cohort of patients with CKD. Graphical Abstract