Non‐alcoholic steatohepatitis has emerged as a major public health problem, and the burden of non‐alcoholic steatohepatitis cirrhosis is projected to increase by 64%‐156% by 2030. The threat is aggravated by the fact that are currently no approved drugs for the treatment of non‐alcoholic steatohepatitis. In this paper, we review the main challenges to drug development in patients with non‐alcoholic steatohepatitis cirrhosis, and describe the opportunities brought by the advances in the understanding of the clinical and pathophysiological nuances of cirrhosis. The design of therapeutic regimens for non‐alcoholic steatohepatitis cirrhosis will vary according to the specific cirrhosis substage (compensated vs decompensated), and the specific mechanistic basis of therapy, targeted either at improving aetiology‐specific pathways and/or at more general aetiology‐agnostic processes. The understanding of the probabilistic expectations for the whole range of potential outcomes, rooted at different mechanistic drivers at each specific substage, will be essential in order to choose adequate estimands and therapeutic strategies for clinical trials and individual patients with non‐alcoholic steatohepatitis cirrhosis. Finally, we provide a summary of the main pitfalls and uncertainties in the design of clinical trials for non‐alcoholic steatohepatitis cirrhosis and discuss potential biomarkers for use in trials and practice for these patients. ACLFacute‐on‐chronic liver failureCCcryptogenic cirrhosisCDclinical decompensationCSPHclinically significant portal hypertensionCVDcardiovascular diseaseELFenhanced liver fibrosisFDAFood and Drug AdministrationHCChepatocellular carcinomaHEhepatic encephalopathyHVPGhepatic venous pressure gradientHyperdynamic circ. Sd.hyperdynamic circulatory syndromeIHVRintrahepatic vascular resistanceMELDmodel for end‐stage liver diseaseNAFLDnon‐alcoholic fatty liver diseaseNASHnon‐alcoholic steatohepatitisOLTorthotopic liver transplantationPBFportal blood flowPHportal hypertensionPROpatient reported outcomeRCTsrandomized controlled trialsT2DMtype 2 diabetes mellitusNon‐alcoholic steatohepatitis (NASH) represents a major public health problem, with the burden of NASH cirrhosis projected to increase 64%‐156% by 2030.There are no Food and Drug Administration‐approved drugs for NASH cirrhosis, and clinical outcomes are the only recommended endpoints for market approval.Therapeutic regimens will vary according to cirrhosis stage (compensated vs decompensated) and the mechanistic basis of therapy (aetiology specific vs symptomatic).A clear definition of NASH cirrhosis, understanding of liver disease biology and detailed patient risk stratification are required for future clinical trials.Non‐invasive tests, eg enhanced liver fibrosis and liver stiffness, are promising biomarkers.1Non‐alcoholic fatty liver disease (NAFLD) has emerged as a major public health threat, and the burden of end‐stage liver disease due to NAFLD is projected to increase from 64% to 156% by 2030.By 2030, cirrhosis and end‐stage liver disease related to NASH are projected to increase worldwide.As shown in Table One recent study in Wales2There are currently no Food and Drug Administration (FDA)‐approved drugs for compensated NASH cirrhosis. Patients with cirrhosis are the most likely to develop hard outcomes . Current trials in patients with cirrhosis capture outcomes related to cirrhosis, such as hepatic encephalopathy, ascites and variceal haemorrhage, as well as the laboratory components of the Child–Pugh score. Improvement in histological fibrosis stage or hepatic collagen content have been also used as primary endpoints of outcome events in trials focused on NASH cirrhosis. However, the reversal of cirrhosis to lesser degrees of fibrosis is an ambitious goal, and the relationship between histological changes in cirrhosis and clinical outcomes has not been characterised. Improvements in fibrosis stage may reflect either true regression or sampling bias.Complication of ascites including any of the following: spontaneous bacterial peritonitis, diuretic‐resistant ascites (refractory ascites), hepato‐pleural effusion.Variceal haemorrhage.Hepatic encephalopathy.Worsening model for end‐stage liver disease (MELD) score to greater than or equal to 15 (this endpoint approximates listing for liver transplant).Liver transplantation.Death from any cause.Currently, the only endpoints recommended by the FDA to support marketing approval in compensated NASH cirrhosis are clinical outcomes.3The structure and focus of therapeutic regimens for NASH cirrhosis will vary according to 2 main factors: (i) the specific substage of cirrhosis at which the therapeutic strategy is directed, and (ii) the specific mechanistic basis of therapy–either targeted at improving aetiology‐specific pathways  or at more general aetiology‐agnostic processes .The classical concept of cirrhosis is histological in nature, and has been traditionally regarded as a static, non‐reversible last stage for all forms of progressive liver diseases.From a clinical standpoint, the occurrence of a first clinical decompensation (CD) indicates a dramatic worsening of prognosis in patients with cirrhosis and enables division into 2 main stages: compensated and decompensated cirrhosis.The compensated stage is the longest phase and can go undiagnosed given its asymptomatic nature. Nonetheless, early identification of patients at this stage would be of paramount importance, since this is precisely the phases at which therapies might be still able to prevent the transition to the decompensated stage, or even lead to a regression to pre‐cirrhotic stages. Within the compensated stage, the presence and degree of portal hypertension is a key predictor of outcome. By integrating haemodynamic data, further distinction of prognostic relevance can be made into an early compensated stage and a late compensated stage.The distinction between the early compensated stage and CSPH is not merely prognostic but also carries pathophysiological and therapeutic implications. In the early compensated stage, the main drivers of progression and outcomes are aetiology‐specific.Once the critical CSPH threshold is reached, the risk of CD increases considerably,Finally, the occurrence of CD signals that intrahepatic and extrahepatic structural and functional adaptations are insufficient and therefore that the patient has progressed to NASH cirrhosis.Considering the poor prognosis in the decompensated stage, transplant‐free survival is recommended as the primary endpoint for Phase III trials.In summary, the understanding of the probabilistic expectations for the whole range of potential outcomes, rooted at different mechanistic drivers at each specific substage of NASH cirrhosis, is essential in order to choose adequate estimands and therapeutic strategies for clinical trials, and tailor therapy to individual patients with NASH cirrhosis.44.1An accurate case definition of NASH cirrhosis is critical for enrolling appropriate patients into clinical trials, but currently there are no published criteria for defining NASH cirrhosis. NASH is a histological diagnosis, but in clinical practice, the term NASH cirrhosis has been increasingly used by physicians to address the forms of end‐stage liver diseases in the presence of known risk factors for metabolic derangement, mainly obesity and type 2 diabetes mellitus. However, the progression of NASH is associated with a loss of intrahepatic fat and diminished inflammatory activity.The presence of a suggestive medical history and/or hallmarks of metabolic syndrome may help to characterise patients with true NASH cirrhosis, with respect to those with unexplained (‘cryptogenic’) cirrhosis (CC).The recent proposal to substitute the term NASH by Metabolic (dysfunction) Associated Fatty Liver Disease (MAFLD)Nonetheless, adoption of the new term is still a matter of debate, and proof of it is that the whole MAFLD concept has not been applied in clinical trials yet, where precise and well‐characterised criteria are still needed to avoid bias and confounders and for regulatory reassurance. In this regard, the Liver Forum recently developed a consensus case definition of NASH‐related cirrhosis for inclusion in clinical trials that may be qualitatively categorised according to the degree of certainty of NASH as the cause of cirrhosis: definitive, probable and possible.BOX 1Abbreviations: NASH: non‐alcoholic steatohepatitis; T2DM: type 2 diabetes mellitus.4.2The drugs currently in development for NASH can be divided into 3 broad categories: metabolic, anti‐inflammatory and antifibrotic. Favourable metabolic effects from a drug are desirable in patients with NASH, but to what extent the partial correction of these metabolic abnormalities leads to a more favourable outcome in cirrhosis is unknown. The biology of clinical decompensation in patients with previously compensated cirrhosis is not fully understood. For example, diabetes arising in liver cirrhosis  has a profound impact on the pathology and natural history of the liver disease.4.3As described above, cirrhosis represents a broader spectrum of disease compared with its usual histological classification (F4), and the main challenge is the stratification of NASH patients with compensated cirrhosis to identify strata for decompensation that represent a clinically meaningful outcome. The expected risk of each outcome changes markedly from stage to stage, and sample size and follow‐up times should vary accordingly. This nuanced view of the different stages of cirrhosis is often overlooked in the design of large clinical trials in NASH cirrhosis. From an operational point of view, stratification by direct or indirect evidence of CSPH  and/or a decreased liver function (Child‐Pugh score ≥6 points) could be used to fine‐tune the assumptions around expected event rates informing sample size, trial duration, etc A more granular and detailed sub‐stratification of patients with NASH cirrhosis and the corresponding choice of outcomes is needed to stimulate therapeutic development in this population.4.4Placebo response represents a major challenge in NASH clinical trials. Patients allocated to placebo arms in therapeutic trials show significant histologic, radiologic and biochemical responses55.1As discussed above, the HVPG remains the most robust and accurate surrogate predictor of outcomes in patients with compensated and early decompensated cirrhosis of different aetiologies, including NASH.5.2In an attempt to mitigate the inter and intra‐observer variability in NASH histology readings discussed in the first section, improved machine‐driven methods to quantify basal amount of fibrosis and changes in time are being increasingly explored in the last few years. A recent paper evaluating a machine‐learning (ML) based‐approach with paired biopsies from 3 large NASH RCTs including patients with advanced fibrosis 5.3A major challenge in drug development is to identify and validate surrogate markers that predict a reduction in progression to hard outcomes. Different exploratory efficacy endpoints have been studied in clinical trials in patients with NASH cirrhosis, including changes in liver biochemistry tests; non‐invasive tests ; markers of apoptosis and necrosis and other histological measures including hepatic collagen and fat content and α‐SMA expression.Functional testing is a novel approach to assess the severity of liver disease and changes in actual liver function in the context of treatment trials, especially in patients with cirrhosis. The HepQuant test simultaneously measure clearance from portal and systemic circulation as well as portal‐systemic shunting.6NASH cirrhosis has emerged as a major healthcare problem and finding effective therapies for patients with NASH has become one of the main unmet clinical needs in hepatology. Drug development in this field will face important challenges, due to the time needed to gather hard outcomes and the unreliable nature of fibrosis as an endpoint. A deeper understanding of the clinical nuances of NASH cirrhosis, and the mechanistic processes driving disease progression at each substage, will hopefully guide therapeutic efforts and appropriate patient selection, informative biomarkers and clinically meaningful endpoints.Jesús Rivera‐Esteban reports no conflicts of interest. Angelo Armandi reports no conflicts of interest. Salvador Augustin is now an employee of Boehringer Ingelheim but was not when the manuscript was written. Elisabetta Bugianesi reports advisory board activity for Boehringer Ingelheim, Bristol Myers Squibb, Gilead, Innova, Intercept, Novo Nordisk.Not applicable.


Evidence suggests children from minority ethnic groups have lower rates of referrals from primary care to CAMHS, are more likely to be referred via involuntary or compulsory routes and less likely to have access to therapies than children from white backgrounds. In order to understand how ethnicity influences individuals and ensure service innovation meet these needs data collected have to be accurate. The Mental Health Services Data Set outlines all children and families receiving NHS care should have ethnicity included as a mandatory data submission and services are performance managed on this.The aim of this audit to review the documentation of ethnicity for service users in CAMHS. We agreed that 100% of patients within York and North Yorkshire (Y&NY) CAMHS should have their ethnicity documented.Integrated Information Centre (IIC) was used to collect data on the documentation of ethnicity for patients under Y&NY CAMHS on 27th August 2020.The total caseload was 4109 patients.823 (20%) had their ethnicity documented as ‘unknown’ (the clinician had entered ‘unknown’ or the patient has ‘declined to disclose’).49 (1.2%) patients had no entry regarding ethnicity (missing).We recommend further exploration to consider why 1 in 5 patients have ‘unknown ethnicity’ documented. We recommend: conducting a refined search considering the percentage of ‘declined to disclose’ and ‘not stated’ within the ‘unknown ethnicity’ section emailing care coordinators for patients with ‘unknown ethnicity’ or ‘missing ethnicity’ conducting a questionnaire to gather the opinions and experiences of clinicians, patients and families when talking about ethnicityreviewing the process for documenting ethnicity to improve accuracy developing staff training, to promote a culture of confidence and curiosity when discussing ethnicity Following this intervention we will aim to re-audit and consider if this has improved the rates of documentation of ethnicity.


Applying purely data‐driven analysis methods, we show that medial orbitofrontal cortex  and the posterior cingulate sulcus (likely area 23c of the posterior cingulate cortex), two sub‐regions of the DMN, modulate the valence of thought‐contents during mind‐wandering. In addition, across two independent experiments, we observed that the posterior cingulate sulcus, a region involved in pain, shows valence‐specific functional connectivity with core regions of the brain's putative pain network. Our results suggest that two DMN regions (mOFC and posterior cingulate sulcus) support the formation of negative spontaneous, nonintentional thoughts, and that the interplay between these structures with regions of the putative pain network forms a neural mechanism by which thoughts can become painful.Many individuals spend a significant amount of their time “mind‐wandering”. Mind‐wandering often includes spontaneous, nonintentional thought, and a neural correlate of this kind of thought is the default mode network (DMN). Thoughts during mind‐wandering can have positive or negative valence, but only little is known about the neural correlates of positive or negative thoughts. We used resting‐state functional magnetic resonance imaging (fMRI) and music to evoke mind‐wandering in  We used resting‐state functional magnetic resonance imaging (fMRI) and music to evoke mind‐wandering, with positive‐sounding music eliciting thoughts with more positive valence and negative‐sounding music eliciting thoughts with more negative valence. We observed that medial orbitofrontal cortex (mOFC) and the posterior cingulate sulcus, two sub‐regions of the default mode network (DMN), modulate the valence of thought‐contents during mind‐wandering, and that the posterior cingulate sulcus, a region involved in pain, shows valence‐specific functional connectivity with core regions of the brain's putative pain network. Results indicate that mOFC and the posterior cingulate sulcus support the formation of negative mind‐wandering thoughts, and that the interplay between these structures with regions of the putative pain network forms a neural mechanism by which thoughts can become painful. The aim, thus, was to modulate the valence of thought contents while controlling for the tempo of the music (and thus for the strength of mind‐wandering), in order to identify differences in DMN activity between positive and negative thought. Moreover, we included rest‐blocks without music, to compare data of blocks with positive or negative music to a neutral baseline condition. Based on our previous studies  were included in the fMRI data analysis. Exclusion criteria were hearing impairment (as assessed with a standard pure‐tone audiometry), musical anhedonia . Likewise, peaceful and sad stimuli had the same average BPM. Thus, positive  and negative  music stimuli had on average the same musical tempo, such that physiological arousal due to beat induction would not differ between positive and negative stimuli.Stimuli were carefully pre‐selected based on pilot‐data to induce four target emotions: “joy”, “sad”, “peaceful”, and “nervous” . Thus, across all participants, 270 valid trials were gathered for each emotion. Participants listened to the music stimuli with the instruction to close their eyes and relax. After each stimulus, thought probes were collected, consisting of 10 questions. These questions were identical to a previous study . No other effects nor any interactions were observed for these variables, nor for any of the other collected items. Thus, our selected stimulus material had a strong effect on the valence and arousal of thoughts.To characterize stimuli with regard to their potential to elicit mind‐wandering and influence the quality of thoughts, stimuli were evaluated in an internet experiment with 2.4In the fMRI experiment, music stimuli were concatenated (separately for each emotion condition) and presented in blocks, resulting in four music blocks . In addition, the experimental paradigm included two rest blocks. Each block had a duration of 5 min. Ordering of the six blocks was pseudo‐randomized (such that the second rest block would never follow directly the first rest block) and counterbalanced across participants. The task for the participants was to relax (in both the rest and the music blocks), and to listen to the music (in the music blocks). At the beginning of each block, participants were asked to keep their eyes closed until the end of the block, when a beep tone signaled to open the eyes and commence the rating procedure. Then, 10 questions were presented visually, and participants responded to each question on a six‐point scale via two fMRI‐compatible response buttons (one in each hand), using their index fingers. The direction of the scales was counterbalanced across trials, to exclude potential motor preparation during the music blocks and thus potential response bias. The wording of the questions was identical to a previous study  at the radiology department of the Haukeland University Hospital in Bergen, Norway. A 32‐channel phased‐array head coil was used. A three‐dimensional T1‐weighted, high‐resolution anatomical image was acquired for each participant using a magnetization‐prepared rapid acquisition gradient echo (MP‐RAGE) sequence . A gradient echo, echo‐planar pulse sequence  sensitive to BOLD contrast was used to acquire functional data. Additionally, the acquisition window was tilted by a 30° angle to the intercommissural plane (AC‐PC); this procedure is helpful in reducing the susceptibility to artifacts in areas such as the orbitofrontal cortex and temporal lobe . Only data from 29 participants of the fMRI were analyzed because of data loss due to technical reasons.2.7Datasets were preprocessed using standard methods implemented in SPM12  and the MIT connectivity toolbox , consisting of slice‐time correction, realignment and reslicing of functional volumes, artifact detection , denoising via regression of average white matter timeseries, average CSF timeseries, 24 Volterra expansion movement parameters and scan‐nulling regressors . The Monte Carlo simulations accounted for anatomical priors through hemispheric symmetry and generated thresholds for cluster sizes and peak z‐values based on the initial threshold and the specific geometrical properties of the images  to control for false positives and obtain the final activation maps corrected for multiple comparisons at the p = .05 level of significance , ECM images from all subjects were entered into a second‐level general linear model and a paired‐samples 2.8r to z transformation, with each gray matter voxel across the whole brain for each subject, for each condition (positive and negative) separately. On the second level, contrasts of positive and negative functional connectivity maps were computed via a paired‐samples t‐test, to obtain the valence‐specific  functional connectivity of the seed cluster. Clusters with significant differences between positive and negative stimuli, in relation to the seed cluster, were identified following correction for multiple comparisons, performed identically as for the ECM analysis, with the exception of setting the corrected level of significance at p = .001 .The ECM results indicated a cluster in the posterior cingulate sulcus at the group level for the contrast negative versus positive music  with the item “How much were you thinking about the experiment versus something else?” on a scale from 1 to 6) on average as moderate . During the music blocks, participants also reported moderate mind‐wandering . Although mind‐wandering was nominally strongest during peaceful music, this difference (compared to the other music conditions) was not significant (corrected for multiple comparisons). Compared with rest, mind‐wandering was weaker during joy, sad, and nervous music , but not during peaceful music (p > .05). Importantly, replicating the results of our preparatory internet experiment  than negative  music , and tended to be more negative during negative music . The arousal of thought contents was higher during fast  than slow  music , but importantly (and contrary to the pilot experiment) there was no significant difference in the arousal of thought contents between positive and negative music (p = .07). Compared to rest, the arousal of thought contents was higher during fast music . No other main effects or interactions were observed for any of the other items. In summary, mind‐wandering emerged during all experimental blocks, the valence of thoughts was more positive during positive music, and the arousal of thought contents was higher during fast music (but did not differ between positive and negative music).During the rest blocks, participants rated their 3.2Given that mind‐wandering emerged during all music conditions, we first investigated whether a similar eigenvector centrality pattern emerged during music and rest. We observed that the eigenvector centrality maps (ECMs) of the rest blocks showed a striking similarity with the ECMs of each of the music blocks : The ECM clusters strongly overlapped in all conditions Figure , with peNotably, this resting‐state network, as assessed using ECM, is reminiscent of the Default Mode Network (DMN), as typically assessed using independent component analysis (ICA): Regions with high eigenvector centrality overlap with the “midline core” of the DMN  music were indicated in the upper bank of the posterior cingulate sulcus, extending medially into the paracentral lobule  and negative (nervous & sad) music . Regions in which eigenvector centrality differed between positive and negative music are shown in Figure z = 2.87), and did not differ between rest and positive music. Thus, negative music increased the functional centrality of neurons in the posterior cingulate sulcus compared to both rest and positive music. Higher eigenvector centrality values during positive (compared to negative) music were indicated in the dorso‐lateral premotor cortex bilaterally (area 6). Contrary to our previous study  explored the functional significance of area 23c using meta‐analytic data, then (second) investigated the functional connectivity of this region, also using meta‐analytic data, and finally (third) computed the functional connectivity of area 23c using the fMRI data of the present study, comparing the functional connectivity of area 23c between positive and negative music in order to specify whether the functional connectivity of area 23c is modulated by emotions. These three steps are described in more detail in the following.The ECM contrast analysis revealed that the centrality of the posterior cingulate sulcus (area 23c of the PCC), varies depending on the valence of music‐evoked thoughts. To aid the interpretation of this finding, we , followed by the label “pain” (posterior z = 5.14). This indicates a role of area 23c in pain.First, we identified the meta‐analytic activation pattern associated with the peak coordinate of the ECM cluster observed in area 23c . That map is shown in Figure Third, based on these observations, we compared the functional connectivity of area 23c with these regions  between the two conditions (positive vs negative) of the present experiment, hypothesizing that area 23c would show stronger functional connectivity with these regions during negative, compared with positive, music. Results of this valence‐specific functional connectivity analysis are shown in Figure 3.4.1z = −3.30, MNI coordinate: −42, −18, 21) and right  parietal operculum (with the cluster in the right POP extending into the posterior insula), as well as in the mOFC . In all of these structures, functional connectivity was stronger during negative than positive music  than during negative‐sounding music (nervous & sad). This observation replicates results of two previous studies  appears to play a role in pain and pain regulation, as suggested by our Neurosynth meta‐analysis of the functional significance of this region. This notion is supported, for example, by an fMRI study using multivariate pattern analysis , including medial orbitofrontal cortex (mOFC), was higher in our previous study during sad‐ than joyful‐sounding music  and mOFC (part of the vmPFC) are subregions of anterior and posterior midline “hubs” of the DMN. The present results shed new light on these DMN regions: Our results indicate that neurons in the posterior cingulate sulcus become more influential during thoughts with negative valence, as reflected by increased eigenvector centrality and increased functional connectivity with SII, insula, and the mOFC. We suggest that the increased functional connectivity of the posterior cingulate sulcus with SII and insula is associated with the function of these areas for pain, and that the increased connectivity with mOFC is associated with the function of the mOFC for the generation of spontaneous thoughts with emotional valence. This interpretation of our results is consistent with findings showing that increased activity in vmPFC and the posterior cingulate sulcus during physical pain tracks depressive symptoms in fibromyalgia , and thus reduce activity in the brain's putative pain system associated with negative thoughts. This assumption is also based on previous data showing that the effects of music on pain are mediated by the valence (pleasant / unpleasant) of the emotions induced  indicated several cortical hubs of other resting‐state networks (RSNs), located in visual, lateral parietal, temporal, and mid‐cingulate cortex. Note that the DMN is one of several RSNs that typically appear in an independent‐component analysis (ICA) of resting‐state fMRI data , and that music has the capacity to modulate the emotional valence of spontaneous, nonintentional thoughts during mind‐wandering. The fMRI results show that several hubs of the Default Mode Network (DMN) have high centrality not only during rest, but also during music listening. According to our findings, area 23c of the posterior cingulate sulcus (a subregion of the DMN) becomes more influential during thoughts with negative valence, as indexed by an increase in eigenvector centrality. Moreover, during negative thoughts, we observed an increase of the functional connectivity of area 23c with secondary somatosensory cortex and insula (two core regions of the brain's putative pain network), as well as with the medial orbitofrontal cortex / ventromedial prefrontal cortex . This reveals that mOFC/vmPFC and the posterior cingulate sulcus (area 23c) comprise the neural basis of negative spontaneous, nonintentional thoughts, and that the interplay between these structures with core areas of the putative pain network form a neural mechanism that can make negatively valenced thoughts painful. Our findings have clinical relevance for the use of positive‐sounding music to reduce rumination and influence the valence of thoughts, thus reducing activity in the brain's pain system associated with negative thoughts.The authors declare no conflict of interest.DATA S1: Supporting InformationClick here for additional data file.


Transition metal hydroxides (M‐OH) and their heterostructures  have recently emerged as highly active electrocatalysts for hydrogen evolution reaction (HER) of alkaline water electrolysis. Lattice hydroxide anions in metal hydroxides are primarily responsible for observing such an enhanced HER activity in alkali that facilitate water dissociation and assist the first step, the hydrogen adsorption. Unfortunately, their poor electronic conductivity had been an issue of concern that significantly lowered its activity. Interesting advancements were made when heterostructured hydroxide materials with a metallic and or a semiconducting phase were found to overcome this pitfall. However, in the midst of recently evolving metal chalcogenide and phosphide based HER catalysts, significant developments made in the field of metal hydroxides and their heterostructures catalysed alkaline HER and their superiority have unfortunately been given negligible attention. This review, unlike others, begins with the question of why alkaline HER is difficult and will take the reader through evaluation perspectives, trends in metals hydroxides and their heterostructures catalysed HER, an understanding of how alkaline HER works on different interfaces, what must be the research directions of this field in near future, and eventually summarizes why metal hydroxides and their heterostructures are inevitable for energy‐efficient alkaline HER. This review brings out the key advancements made in the field of alkaline HER with metal hydroxides and their heterostructures and also provides a detailed and critical analysis of strategies and perspectives used with highlights on future prospects at the end. In such a highly acidic solution, regardless of the nature of the surface  that catalyse HER under applied potential, HER can proceed via two different paths namely Volmer–Heyrovský mechanism and Volmer–Tafel mechanism. In both paths, Volmer step is inevitable. Each step involved in acidic HER is given below Eqs. , 2, 3.[5ads) would be facile in a solution of extremely low pH. The following step could either be Tafel or Volmer depending on the work function, density of states, and the local crystallographic geometry of the catalytic sites.[ads in closer proximities tend to evolve hydrogen following Tafel path and this is the most efficient path for HER that require minimum work .ads is larger than the sum of Van der Waals radii of two S−Hads bonds  tend to follow the Heyrovský step instead.−1 are said to follow Volmer–Tafel mechanisms and others with Tafel slopes higher than 45 mV dec−1 are said to preferably follow the Volmer‐Heyrovský mechanism. The selectivity between these two mechanisms shifts towards Volmer‐Heyrovský mechanism with the increasing Tafel slope until 120 mV dec−1. In acidic conditions, it is very rare to see a HER electrocatalyst that could have an abnormal Tafel slope (>120 mV dec−1) as the solution is rich in protons and the Volmer step is not hindered/dependent by any other reaction that must occur along. Nonetheless, it is also to be emphasized here that the Tafel analysis of HER in acidic conditions can be deceiving as proton discharge and the delivery of H2 molecule are very fast in proton‐rich solutions. Therefore, the measured Tafel slopes often reflect the mass transport limitations rather than reflecting the mechanism by which HER is being catalysed.As can be witnessed, proton adsorption and discharge that forms adsorbed H atoms (Hads/H2(g). Here, the three steps of HER in alkali are listed below [Eqs. In alkaline conditions where the probability of finding a free proton in solution is nearly zero and the Volmer step (proton adsorption and discharge) has to rely always on a water dissociation reaction which is thought to be accompanied by the Volmer reaction and occurs separately prior to the Volmer reaction in the vicinity of electrode surface according to the beliefs of another part of researchers.[low Eqs. , 5, 6.(4j0) of HER/hydrogen oxidation reaction (HOR), Tafel slopes, and enthalpy changes (ΔH) of activation for a Pt(111) surface reported by Markovic and co‐workers.[From the Volmer and Heyrovský steps of alkaline HER, it can be noted that the interface is given an extra burden to carry which is the water dissociation step providing the required free proton for the reaction to proceed. This implies that HER in alkali is indeed harder than acidic HER. In addition, it could also be noted that a hydroxide anion is produced locally at the surface of the electrode with the expense of a water molecule, which further makes things complicated as it will lower the concentration of water molecules and pushes the equilibrium of water dissociation back. These insights from the mechanism suggest that alkaline HER is an energy intensive process than acidic HER and even the state‐of‐the‐art Pt struggles to perform efficient alkaline HER.−1 implies that Pt(111) surface was following Volmer–Heyrovský mechanism in acid whereas an abnormal Tafel slope of 150 mV dec−1 imply that the Volmer step of HER is dependent on another reaction (water dissociation in this case) for it to proceed via proton adsorption and discharge. In alkaline conditions, it is very common to witness such high and abnormal Tafel slope values (>120 mV dec−1) that primarily indicate that the reaction is controlled by the water dissociation step and the rate determining step (RDS) is the first electron transfer reaction . Hence, any HER electrocatalyst that could have a Tafel slope value lesser than 120 mV dec−1 is considered to be better in alkali and the catalysts that could follow the Volmer‐Tafel mechanism in alkali are rare which often contain Ru or Pt with metal hydroxide or heterostructured metal hydroxide phases.[As one can clearly see from Figure 3E0) under ideal conditions. However, in real cases, there are other phenomena  that add further workload and makes the electrode to demand a certain quantity of additional energy  to begin the reaction of interest. Beyond this onset overpotential, for every increase required in terms of current density will also increase the overpotential. Hence, it is desired to have a catalyst that could have lesser onset potential. An important characteristic of this onset overpotential is that it is intrinsic to the catalyst's surface properties and does not vary with the varying loading/specific surface area (SSA) of an electrocatalyst. This characteristic of onset overpotential places it among other important activity markers of a HER electrocatalyst. Nonetheless, there are several examples of electrocatalysts which were shown to have relatively higher onset overpotentials yet deliver better activity at higher overpotentials (current densities) due to various reasons among which increased SSA ) as a result of nanostructuring and increased loading are being the primary contributors to the overall enhancement witnessed.[2 nanowires electrocatalysed HER in acid and alkali  devices evaluation.[−2 are also often reported along with onset overpotential and the overpotential at 10 mA cm−2. However, the recent comprehension is that any catalyst that is capable of delivering 1 mA cm−2 at lower overpotentials are considered better and they can be scaled up to improve their activity extrinsically depending on the requisites. Though onset overpotential and overpotential at any fixed current density (in cathodic direction) are primarily controlled and dictated by the hydrogen overpotential deposition (Hopd), hydrogen underpotential deposition (Hupd) was earlier thought to play crucial roles in determining the HER/HOR activity of electrocatalysts in water electrolysers and fuel cells. Hydrogen binding energy (HBE) of Hupd is highly pH dependent and it shifts toward more negative values  with increasing pH as reported by Yan and co‐workers for Pt surfaces  is inversely related to the HER activity of Pt surfaces they studied. Laying the foundation on this finding, Zheng and co‐workersj0, the current density measured for HER at reversible overpotential) against Hupd desorption peak  are highly active for HER. As indicated earlier, the hydrogen desorption/adsorption potential was found to shift anodically with increasing pH which justifies poor HER activity of electrocatalysts in highly alkaline solutions. Despite being an accurate activity marker, this relationship between j0 and Hupd desorption potential cannot be made for all electrocatalysts especially for semiconducting surfaces that hardly show such Hupd characteristics. This made this activity marker inapplicable for most of the recently evolved HER electrocatalysts. Besides, the HBE proposed by these studies is in fact inaccurate in alkaline solutions. This is because HER is pH dependent like Hupd but not Nernstian in nature like Hupd. As a result, the guesses that could be made  only from HBE may not be as impeccable as it was once expected to be in predicting the activity trends for alkaline HER. For example, the HBE was calculated to become highly negative for Pt with the increasing pH. However, the loss of HER activity by 2 to 3 folds in alkaline solutions was not justified.GOH*) at the potential 0.0 V vs. RHE along with HBE for a catalyst to have a facile water dissociation step in alkaline HER. In this study, metals such as Mo, Re, Ru, Rh, and Ag were decorated on a Pt(553) single crystal electrode and their HER activity in alkali was screened. When the rate of HER was plotted against the ΔGOH*, it led to a classical Volcano relationship  can act better in water dissociation step which is the bottleneck of efficient HER in alkali , F denotes the Faraday constant, and Γ indicates the number of active sites. Hence, the calculated TOF is expressed as the amount of hydrogen produced per second.All those overpotentials mentioned above are thermodynamic parameters. On the other hand, activity is also controlled by the kinetic parameters. Two other main kinetic parameters that researchers use in HER electrocatalysis are Tafel slope and turnover frequency (TOF) in which the former one qualitatively suggests how faster the HER is occurring on the interface with certain values that are often closer to 30, 60, 90, and 120 mV decThus TOF simply tells us how quick an interface can be in catalysing HER under applied potential and serves as an important activity marker.−1 and the number cycles may vary from a few hundred to thousands.[upd desorption potential , and a lower Tafel slope. Similarly, exchange current density (j0), TOF, and coulombic efficiency should be higher. Meanwhile, the effects of substrate electrode's dimension and conductivity and the ways in which the catalyst is supported  should not be left aside. Depending on the conductivity and geometry of the substrate electrode, the observed activity of the same electrocatalyst can vary significantly. Such variations are highly pronounced particularly when the use of different substrate electrodes causes uncertainties in the catalyst's loading. Also, foam and fiber type 3D substrate electrodes often get access to the electrolyte beyond what is actually exposed via the capillary action. An elaborate discussion on the mesoscopic effects of substrate electrode geometry can be found in our earlier perspective,Selectivity and stability are two other important perspectives of HER electrocatalyst evaluation that determines the fate of the electrocatalyst under study in promoting it to large‐scale water electrolysers. Selectivity is defined as the percentage efficiency of an electrocatalyst in using the applied energy  selectively for the desired reaction (HER in this case) which is commonly termed as Faradaic efficiency/coulombic efficiency.[4−2, and TOF are benchmarked while also indicating loading of catalysts which play crucial roles in altering overpotential at 10 mA cm−2 and TOF at the end.As stated earlier, metal hydroxides have recently been found to present at least on the surface of every non‐noble metals‐based HER electrocatalysts in alkali as a consequence of displacing action of highly electronegative, nucleophilic, and a relatively strong field ligand hydroxide.[5hcp arrangement, and multi‐metallic LDHs which is also called layered triple hydroxides (LTHs) when there are three different metals. However, LTHs vary in no crystallographic aspects when compared to LDHs. Nickel and cobalt hydroxides have also been shown to have appreciable HER activity in the alkali of which Ni(OH)2 always outperforms Co(OH)2 with a significantly higher margin in overpotentials. A very first and a detailed account on the HER  activity of Ni(OH)2 was reported by Corrigan and Bendert in the late 80s.2 on HER activity . These pristine metal hydroxides can have different crystallographic structures such as layered double hydroxides (LDHs), β‐hydroxides with a y Figure –c. Their2 Figure .2 which is justified by its strong affinity towards forming the structurally rigid trivalent hydroxide. Chemistry of Pb and Ag are almost similar, they both have a similar density of states, both get precipitated with hydrogen sulphide, both form black oxides upon exposure to atmospheric oxygen in the presence of moisture. In contrast, none of the other metal ions studied along with these two have such similarities in their chemistry. Since then, advancements made with pristine hydroxide materials based HER electrocatalysts for alkaline electrolytes remained underdeveloped until the transfiguring nanostructuring of multimetallic hydroxide came into play. At the beginning of this decade, there was a renewed interest in re‐examining first‐row transition metal hydroxide for alkaline HER electrocatalysis. Hall and co‐workers2 for a longer time period gradually increased the HER activity which proved once again that a hydroxide phase of Ni is better active in alkaline HER than the fresh metallic surface of the same.Interestingly, coprecipitated Cr had poisoned the HER activity of Ni(OH)2+/Ni3+ redox couple was shifted cathodically with the increasing Co content and the same had also lowered the HER overpotential. Unexpectedly, only Co(OH)2 delivered better activity than both pure Ni(OH)2 and all other combinations of Ni and Co in the binary hydroxide they prepared. Despite the fact that a binary metal hydroxide with an optimal composition must show better HER performance than their monometallic counterparts, this observation stood out of the order. A careful observation on mass loading that they determined from TGA analysis showed clearly that Co was higher in loading (by weight percentage) than all other catalysts. This could be the reason for observing such a standout result. However, their study showed that Ni‐Co hydroxides of ratio 1:1 and 1:0.4 provided a better compromise between activity and stability. Following this study, Bai and co‐workers−2 at just 77 mV from the reversible potential of hydrogen evolution. However, such an improved performance was obviously due to the 3D topology and huge mass loading of the catalyst which in turn was reflected by the huge double layer capacitance that they observed when compared to other catalytic interfaces taken along. A similar Ni‐Co LDH fabricated on Ni foam with a relatively lesser loading by Liu and co‐workers−2. These two contradicting reports testify that besides intrinsic activity changes, mass loading, specific/ECSA, and mesoscopic effects play vital roles in determining the HER performances of these binary metal hydroxides. Zhao and co‐workers2 improves the HER performance by increasing the electron density at Ni centres via pushing the electrons that introduced Co had away from it when polarized cathodically. This pushing effect eased the Volmer step of HER and led to improved performance. On the other hand, when they added 10 % of Fe which longs for electron under applied potentials decreased the activity.Later, hydroxides that had two or more metals were found to perform better than these monometallic hydroxides as they offer a variety of active sites with different but favourable hydroxide/water adsorption energies. This helped these catalysts to lower the threshold of Volmer step in alkaline HER.2, the HER performance was even worsened. These observations showed that a binary phase with a suitable metal with an appropriate electron donating ability is essential to observe a significant HER enhancement. Their observations on HER overpotential, Tafel slope, and double layer‐capacitance of Ni(OH)2 with different proportions of Co and Fe have indicated that Ni0.9Co0.1 hydroxide was the optimal system  than the one reported by Rajeshkhanna and co‐workers2 and observed better activity. Nonetheless, the performance what they witnessed was still poorer than the ones attained with NiCo and CoFe LDH catalysts. Among the NiFe LDH based HER reports, Guo and co‐workers0.9Co0.1 LDH. However, given that Fe in 3+ state in NiFe LDH is more electronegative than that of Ni in 2+ state in NiCo LDH, the observed difference in HER performance between these two is justified. This fact was actually later supported by the in situ Raman study reported by Qiu and co‐workers.3+ cation was diminished and led to gradually increasing HER performance as such reduction of Fe3+ progressed. They also revealed that alkaline HER with NiFe LDH begins with the adsorption of water at Fe3+ site as it is more electron deficient and proceeded further to form Ni‐H intermediate via a coupled proton‐electron transfer (CPET) mechanism. This Ni‐H intermediate then could be able to evolve hydrogen either via the Heyrovsky mechanism or Tafel mechanism  rather than the intrinsic catalytic activity changes provided that Cr3+ does neither donate nor withdraw electrons easily as it is already having a half‐filled 2gt level  which is more stable than electron donating Co2+ and electron withdrawing Fe3+ in NiCo and NiFe LDHs, respectively. An unusual way of improving the HER activity of Ni(OH)2 was reported recently by Zhang and Hu−2). However, the stability test performed for 12 h showed a significant increase in overpotential which is attributed to the leaching of F in alkaline medium just like any other halide ion does. Hence, this approach did not attract much attention lately to improve the HER activity of other similar HER electrocatalysts. Having a synergistic support with a HER electrocatalyst had always been shown to play benefitting roles.Interestingly when both Co and Fe were added (20 % cumulatively) to Ni(OH)m Figure –f. Thougm Figure . Other t2 in alkali can be improved significantly by making a composite of Co(OH)2 electronically conducting polyaniline (PANI) fibres. This flexible electrode demanded less than 100 mV as overpotential to deliver 10 mA cm−2 for HER. Later, Jia and co‐workers−2 with lower overpotential. However, as there was no information on the loading of the catalyst, no justifiable comment or correlation can be made with the activity trend being discussed here. Similarly, Bhowmik and co‐workers2 is the best HER electrocatalyst and NiCo LDH takes that spot in the category of binary metal hydroxides‐based HER electrocatalysts because of the optimal electronic configuration of Co2+ ion that promotes the Volmer step.Conductive and nanostructured carbons  with and without heteroatoms  are such proven synergistic supports in electrocatalysis research.2.5Co0.5Fe) for the same system that performed relatively better albeit the differences were very small when compared with NiFe and Ni2CoFe systems. Later, Babar and co‐workers3+). This is yet another trivalent cation with a stable 2gt level (empty) in an octahedral field of a LDH phase just like Cr3+ which also had a stable 2gt level  in an octahedral field of a LDH phase. Hence, it did not impose any notable activity change when compared to the activity of NiFe LDH systems discussed above  heterostructures in 0.1 M KOH 2 were actually enhancing the HER activity of Pt(111) surfaces whereas a significant loss of activity is witnessed with Mn(OH)2 and Fe(OH)2. This is justifiable given that Fe2+ in the low‐spin state has completely filled 2gt level and Mn2+ high spin state has half‐filled 2gt and ge levels in an octahedral field making them both stable. In other words, because of these stable electronic configurations, Mn2+ and Fe2+ ions tend not to donate or withdraw electrons which are necessary for drawing water molecules near hydrogen evolving metal sites. On the other hand, Ni2+ and Co2+ have unpaired electrons in their ge orbitals which are essential in deprotonating water molecules by donating them which in turn populate the nearby metal (Pt) site with necessary protons to evolve hydrogen efficiently. Between Ni2+ and Co2+, the former is better for enhancing HER as it does have two unpaired ge electrons. This also explains the exemplary HER activity of NiCo LDH materials among all other binary metal hydroxides. However, this does not mean that the electronic properties of the metal cations in the metal hydroxide phase alone contribute to alkaline HER enhancement. This was first shown by the work of Subbaraman and co‐workers.+ cations into Ni(OH)2 layers that acted as a strong Lewis acid, they were able to achieve a further weakening of the H−OH bond in water. Such an additional H−OH bond weakening promoted the water dissociation step by Ni(OH)2 phase and subsequently enhanced its alkaline HER activity when interphased with Pt(111). Specifically, a 65 fold HER activity enhancement was witnessed with Pt(111)/Ni(OH)2 heterostructure when 0.001 M of Li+ cations were added to 0.1 M KOH.2 with various other metals such as Ru, Ir, Cu, Ag, Au, V, Ti, and Ni and including Pt earlier was Danilovic and co‐workers 2 system more intensively than others by changing various structural properties of both Pt and Ni(OH)2 counterparts. Yu and co‐workers2 that exist in alkali in the potential window of HER study. They found that the layered alpha phase was poorer than the rock‐salt structure having a beta phase as the latter one improves the kinetics of the Volmer step via a facile water dissociation mechanism. Since it is established that improved electrochemical access to a maximum of Ni(OH)2 in the Pt/Ni(OH)2 heterostructure is a key to improve the HER activity further, Yuan and co‐workers2 decorated with Pt can deliver better HER activity as amorphous materials have always been benefitting water splitting electrocatalysis with improved ECSA. An interesting work of fabricating undercoordinated PtMn alloy and defect rich Ni(OH)2 heterostructure was made by Wang and co‐workers2. Yu and co‐workers2 and when the PtNi:Ni(OH)2 ratio was 1:0.2, the best HER performance was achieved. Beyond just alloying, Pt was structured into different shapes at the nanoscale level as nanoparticles and nanowires and then heterostructured with Ni(OH)2 by Yin and co‐workers2 heterostructure. It was Ledezma‐Yanez and co‐workers2 catalysed HER in alkali using which Sarabia and co‐workers2 heterostructure interface by varying the proportion of Ni(OH)2. They found that the increasing Ni(OH)2 proportion increased the HER activity here in this case too. Such enhancement was even highly pronounced when the flow‐cell was used which enabled relatively more access to interfacial water. However, McCrum and Koper2 were only shown to be beneficial in alkaline HER, some of us recently discovered that a similar enhancement in HER can even be obtained with NiFe LDH by decorating Pt NPs. When the concentration of Pt precursor used to prepare Pt@NiFe LDH heterostructures was increased, the HER activity was also improved 2, and as well to CoNi LDH and observed a similar HER enhancement. Other than Pt, Ru, and Cu, metals that were shown to bring out such HER enhancements were Mn with cobalt carbonate hydroxide, Ni with Ni(OH)2, Pd with NiCo LDH, Au with CoNi LDH, and W modulated Co(OH)2.[2 was the only interface that delivered better HER activity than Pt/C.−2 with different loadings and hence, we solicit the vigilance of the readers to not to take this order exactly as their actual HER activity trend.Yu and co‐workers72/CoOOH) was interfaced with an oxide phase of a dissimilar metal (PtO2 of Pt) was reported by Wang and co‐workers.x heterophase with NiFe LDH could enhance its HER just by the way in which Co2+ acted by pushing the electron away from it to lower the energy of water dissociation as Ce in CeOx existed in both 3+ and 4+ states. However, the magnitude of HER overpotential lowering is very low when compared to the overpotential lowering brought up by Co2+ in other systems. Another example of a metal oxide‐metal hydroxide heterostructure with partially different metal centres was reported by Wang and co‐workers2O4 on Ni foam over which NiFe LDH was grown by using a hydrothermal reaction. The exact intension of this work is still elusive as neither NiFe LDH is a better HER electrocatalyst nor Co3+ ions in the spinel NiCo2O4 is capable of lowering water dissociation energy by donating electrons. However, the observed enhancement in HER activity was significantly higher and we believe that such enhancement could have possibly been brought by the in situ formation of Co2+ species under the applied reductive overpotentials. Nonetheless, no efforts were made in this work to find out any such in situ presence of HER enhancing Co2+ species.In this series of metal hydroxide heterostructures with metal oxides, mostly LDHs were studied with an oxide heterophase of the same metal ions or with different ones. The only study where a monometallic hydroxide/oxyhydroxide (Co(OH)2O4 with an inverse spinel NiFe2O4 and interfaced it with NiFe LDH which had electron donating Fe2+ ions in the tetrahedral field. As a result, a significant improvement in HER performance was witnessed. However, the lowering in overpotential was still higher with NiFe LDH‐NiCo2O4 catalyst reported by Wang and co‐workers.2O4‐NiCo LDH. These studies have shown that not only a second metal of an appropriate electronic configuration or a metal heterophase but also an oxide heterophase of similar or dissimilar metals that could regulate the Volmer step can bring out notable enhancement in HER activities and imply the importance of having such heterostructures. Figure However, Wu and co‐workers2 on carbon fiber paper (CFP) followed by hydrothermally sandwiching the same with the best binary hydroxide (NiCo LDH) HER electrocatalysts. Activity enhancement brought up here were mainly due to intrinsic catalytic activity enhancement rather than a consequence of ECSA which was indicated by a large lowering HER onset overpotential and a marginal increase in double layer capacitance 2  delivered the best performance .Beyond metal oxides, chalcogenides of Co, Ni, Fe, Mo, and W were also interfaced with monometallic hydroxides and LDHs to realize efficient enhancement HER activity in alkali. Hu and co‐workerse Figure . Zhu ande Figure . Yang an0.85Se2 heterophase rapidly. This method has additionally benefitted the HER activity improvement by increasing ECSA as a result of surface amorphization. As a result of collective benefit from both heterostructuring and amorphization, more than 100 mV of overpotential lowering was witnessed in alkaline HER at 100 mA cm−2. This method provides a facile path for heterostructuring other non‐oxide/hydroxide materials that can perform better in alkaline HER.However, when either Co2 over Ni2P thereby forming a heterostructure witnessed a significant HER activity enhancement. They also revealed that the time of hydrothermal treatment and the associated thickness of Ni(OH)2 layer could influence the activity to a greater extent. Their results showed that a 10 h hydrothermal treatment was optimal in attaining the best HER enhancement out of this system. Zhang and co‐workers2P was prone to surface hydroxylation even under reductive potentials that degraded the activity. However, Su and co‐workers−2 could form undercoordinated Co(OH)x species over CoP that helped them to realize a better HER activity. Like the metal chalcogenide interfaced metal hydroxide systems, metal hydroxides interfaced with metal phosphides  do also follow the same mechanism of HER where the hydroxide phase facilitates the water dissociation step and metallic metal phosphide perform HER by forming hydridic intermediates. All these catalysts are benchmarked taking the overpotentials that they demanded at 10 mA cm−2 in Table Metal phosphides interfaced metal hydroxide heterostructures are also reported to be a class of highly active HER electrocatalysts next to metal oxides and metal chalcogenides interfaced metal hydroxide heterostructures. Zhou and co‐workers−2. This geometrical area normalized current density is highly dependent on the loaded mass of the catalyst.All the above benchmarking tables Table –3 displa−1, any electrocatalyst that is having a Tafel slope ≤50 mV dec−1 can be considered a better active electrocatalytic interface. We have also shown in one of our recent studies that loading tends to affect Tafel slopes too but not as extensively as it does to the geometrical area normalized current densities and the corresponding overpotentials determined from it.This implies that the overpotential based benchmarking could be potentially wrong and misleading. Hence, to have an alternative view on the activity trends among all these catalysts, we portrayed all these catalysts discussed in each category according to their Tafel slopes Figure  which pr8−1 and even higher. Metal hydroxide surfaces, on the other hand, are capable of facilitating the tedious water dissociation step because of their ability to coordinate reversibly with water and hydroxide ligands as both of them occupy closer places in the spectrochemical series. As a result, water molecules that coordinate with a metal cation site in a metal hydroxide surface can easily break the O−H bond of water when compared to the noble metal surfaces. This facileness of water dissociation with metal hydroxide surface enriches it with short living protons which can immediately undergo discharge to form the hydridic bond with a nearby catalytic site.It is now certain that the efficiency of alkaline HER is greatly dependent on the efficiency of water dissociation into proton and hydroxide at the cathode which concurrently forms the hydridic intermediate with the catalytic site. This is the typical Volmer step of alkaline HER. This step of the reaction is so difficult as it produces more hydroxide at the interface which is already populated densely with it. Hence, the existence of a high concentration of hydroxide ions on the cathode surface pushes the water dissociation equilibrium backwards. From our ongoing discussions on the HER activity trends observed with metal hydroxides and their heterostructures, a graphical sketch Scheme  is drawn2 is shown to be the better one as it dissociates water and concurrently forms hydridic bond by donating ge electron(s). In binary metal hydroxides, NiCo LDH is the best as they both have unpaired eg electrons that facilitate both water dissociation and hydridic bond formation by “pushing” mechanism according to Zhao and co‐workers.2 heterostructured with Pt and Ru is the best as Ni(OH)2 splits O−H bond in water and the metallic counterpart (Pt or Ru) forms the hydridic intermediate concurrently which in turn facilitate HER. LDHs and other multi‐metallic hydroxides are also shown to exhibit similar activity trends when they are interfaced with Pt and Ru. However, Cu‐interfaced metal hydroxide and LDH heterostructures get benefitted from the better electronic conductivity of Cu. Hence, they impart better enhancement when they are sandwiched or wrapped around with a suitable metal hydroxide or LDH co‐catalyst. This is because metallic Cu tends to form Cu+ and Cu2+ species at potentials that are closer to HER and HOR when exposed directly to the electrolytes which cannot catalyse the Heyrovský and Tafel reactions efficiently. Besides, oxygen containing Cu+ and Cu2+ are well‐known for their poor HER activity which is one of several reasons why they are attractive for CO2 reduction.2 in alkali) is ascertained once again to be controlling alkaline HER efficiency. This was revealed from the relationship between water dissociation overpotentials and the point of zero charges (pzc) of various water dissociating catalysts placed on the locally alkaline side of a bipolar membrane (BPM) , metal chalcogenides , and metal phosphides  that are interfaced with them. Among pristine metal hydroxides, Co(OH)) Figure . Catalysx on CoP surfaces. Hence, it is concluded here that having a metal hydroxide heterophase with metal ions of appropriate electronic configurations (preferably with unpaired ge electrons) with known metal/metal chalcogenide/metal phosphide catalyst is the key to achieve better efficiency in alkaline HER.It is recently comprehended that all non‐oxide/hydroxide HER electrocatalysts that were previously reported to be active in the alkaline media were actually forming a layer of hydroxide on their surface which in turn contributed significantly to the overall catalytic process.[9operando spectroelectrochemical studies of alkaline HER with all the above‐discussed metal hydroxide catalysts and their heterostructures may even lead us to achieve fascinating results and could improve our understanding. Meanwhile, they could also prove our current understanding of alkaline HER be incorrect and provide other exciting insights. Hence, we sincerely hope that these analytical tools will play critical roles in the advancement of alkaline HER electrocatalysis. Other than this, the performance of every catalyst under a large A/V condition (large electrode surface area (A) with smaller electrolyte volume (V)) at elevated temperature which is the typical industrial condition may vary significantly.As it is understood now that water dissociation plays a key role in determining the efficiency of an alkaline HER electrocatalyst, several works have now been focused on this particular part of the overall HER electrocatalysis. Meanwhile, it is also important to concentrate on the Heyrovsky and or Tafel steps. Although these two steps of HER primarily depend on the Volmer step, the bond strength of hydridic intermediate formed with the catalytic site also matters significantly. In our earlier review,As the availability of water molecules at the interface is crucial, flowing electrolyte will refresh the surface with a new electrolyte solution and will lower the chances of additional basification as a consequence of water dissociation which has the tendency to lower the HER kinetics. Hence, the mesoscopic effects of water electrolysers must be taken into account in the evaluation stage too.102 and other related systems. When there is only metal hydroxide, the same metal centres which perform water dissociation do also form hydrogen evolving hydridic intermediates. However, they are relatively stronger in bond strength than the ones formed with a metal atom or the chalcogenide/phosphide anion site in their heterostructures. As a consequence of this, metal hydroxides alone were poor in catalysing HER in alkali. However, if the electronic configuration of the metal ions in the metal hydroxide catalyst being studied is appropriate (i.e. having unpaired ge electrons to readily donate and dissociate water) and the hydridic intermediate formed with them are of optimal bond strength, they could perform relatively better than other metal hydroxides. An example is Co(OH)2 with a conductive carbon support. Having understood that interfacial water structure and its dissociation control the overall efficiency of alkaline HER, we are in an urge to study not only the electrode surface but also the interfacial water structure, electrical double layer, and their reorganization while varying the applied potentials. This can give a more valuable understanding of alkaline HER and the way it does work. This is expected to be accomplished via several in situ and or operando spectroelectrochemical studies to be done in the future. Besides, concentrating on the mesoscopic effect of the electrode and cell is also equally important under large A/V condition to truly realize a better HER performance under industrial operating conditions. With this, we conclude here that alkaline HER will step into a new era of its development in the upcoming years provided that the predicted directions of research in this field will lead so. Eventually, this may end the quest for an energy‐efficient alkaline HER with affordable electrocatalysts  that outperformed Pt/C already at all overpotentials.Unaffordability of acidic OER electrocatalysts led to the development of alkaline water electrolysers with earth‐abundant OER electrocatalysts albeit that came at a price of compromised HER activity in alkali. Absence of free protons in alkali made the relatively simple and straightforward HER tedious and complex even with the state‐of‐the‐art electrocatalysts. In alkaline HER, to get the necessary localized proton rich environment, it is essential to cause the water dissociation step prior to the classic Volmer step of HER. Hence, in an alkaline medium, the water dissociation and concurrent proton discharge that form hydrogen evolving hydridic intermediates are considered as the Volmer step which controls the overall efficiency of a given electrocatalyst to a greater extent. From recent attempts of using metal hydroxides and their heterostructures as HER electrocatalysts in alkaline media, it is now understood that the metal hydroxide phase facilitates the water dissociation. This is because of their ability to reversibly coordinate with both water and hydroxide ligands which are positioned closer to one another in the spectrochemical series. This has been the reason for all the enhanced HER activity witnessed with Pt‐Ni(OH)The authors declare no conflict of interest.Sengeni Anantharaj obtained his undergraduate and postgraduate degrees in chemistry from The Presidency College affiliated to University of Madras, Chennai in 2011 and 2013, respectively. Later, he obtained his PhD in 2018 from CSIR‐Central Electrochemical Research Institute (CECRI), Karaikudi, Tamil Nadu, India. Currently, he is availing the prestigious JSPS Postdoctoral Fellowship at Waseda University since January 2019. His research interests include performance‐driven design of electrocatalysts, energy conversion (both fuel‐forming and fuel‐consuming) electrocatalysis, electroactivation, and anodization.Suguru Noda received his PhD in 1999 from The University of Tokyo, became an assistant professor and associate professor there, and then joined Waseda University in 2012 as a full professor. He is a chemical engineer conducting research in the field of materials processes. He is recently focusing on practical production of carbon and silicon nanomaterials such as carbon nanotubes and silicon films/nanoparticles, and applying these materials to energy and electronic devices.Vasanth Rajendiran Jothi is a Graduate Researcher in the Department of Chemical Engineering at Hanyang University, Seoul. He works in Prof. Yi's group on electrocatalysis projects for hydrogen evolution and water oxidation. He completed his MS at Hanyang University, Seoul, and his undergraduate studies at PSG College of Technology, Kovai, India. He served as a Junior Research Fellow for research projects funded by the Indian Space Research Organization (ISRO). His research interests lie in the electrochemical conversions that are relevant for renewable fuel production.SungChul Yi received his bachelor's diploma in 1981 from the Hanyang University and received his PhD degree (1987) on nonequilibrium thermodynamics and transport phenomena under the mentorship of Prof. R. Rowley at the Brigham Young University. He is currently a Professor of Chemical engineering at the Hanyang University with a research focus on Fuel cells and electrocatalytic water splitting.Matthias Driess is a full professor of metalorganics and inorganic materials at the Department of Chemistry of Technische Universität Berlin. He obtained his PhD degree and completed his habilitation at the University of Heidelberg in Germany. He serves as a deputy of the Cluster of Excellence UniSysCat and is a Director of the UniSysCat‐BASF SE joint lab BasCat, and of the Chemical Invention Factory (CIF) for Start‐ups in Green Chemistry.Prashanth W. Menezes received his PhD in 2009 from the Max Planck Institute for Chemical Physics of Solids in Dresden in solid‐state and structural chemistry. He then joined the Technische Universität München in 2010 to work in the direction of inorganic chemistry with a focus on novel materials. In 2012, he joined Prof. Driess at the Technische Universität Berlin and since then serves as a group leader for inorganic materials. His research focuses on the design, development, and structural understanding of novel unconventional catalysts in heterogeneous catalysis, especially in the area of redox oxygen catalysis, and (photo)electrocatalytic water splitting.


Almost all organisms grow in size during their lifetime and switch diets, trophic positions, and interacting partners as they grow. Such ontogenetic development introduces life‐history stages and flows of biomass between the stages through growth and reproduction. However, current research on complex food webs rarely considers life‐history stages. The few previously proposed methods do not take full advantage of the existing food web structural models that can produce realistic food web topologies.Nature, 2000, 404, 180–183) to generate food webs that included trophic species with a life‐history stage structure. Our method aggregated trophic species based on niche overlap to form a life‐history structured population; therefore, it largely preserved the topological structure of food webs generated by the niche model. We applied the theory of allometric predator–prey body mass ratio and parameterized an allometric bioenergetic model augmented with biomass flow between stages via growth and reproduction to study the effects of a stage structure on the stability of food webs.We extended the niche model developed by Williams and Martinez  to generate food webs that included trophic species with a life‐history stage structure. We then applied the theory of allometric predator–prey body mass ratio to parameterize an allometric bioenergetic model augmented with biomass flow between stages via growth and reproduction. When life‐history stages were linked, more food webs persisted and persisting food webs tended to retain more trophic species. These factors include hierarchically ordered feeding  and connectance  as input parameters , is determined by first drawing a random variable, ηi, from a beta distribution calibrated to obtain the desired connectance and then multiplying ηi by the niche value for i(ri=ηini). The center of the feeding range, ic, is randomly chosen from a uniform distribution in ri2,ni, and the range is then determined as ci‐ri2,ci+ri2. Therefore, species with larger niche values tend to have larger feeding ranges. The ranges are set such that cannibalism is allowed . All the taxa whose niche values fall in the feeding range of another are regarded as the prey of the latter. The taxa with no prey are identified as basal taxa . The taxon with the lowest niche values is designated as an autotroph. We discard disconnected webs, webs with connectance beyond a given tolerance level (Cerror), and webs with taxa not connected to a basal taxon.The niche model requires the number of trophic species  are ordered along the one‐dimensional niche space. The feeding range, aritinez .T) and the prey‐averaged trophic level (T2), to each taxon  and the prey‐averaged trophic level . To create a stage‐structured fish taxon, we first selected a species with the highest T2  that was greater than 2 (Thfish), indicating that this taxon ate at least one nonbasal taxon  of the union of the two and whose niche value was smaller than and closest to the focal taxon's niche value, to become the next lower stage. This stage became the next focal taxon, and we repeated the steps until either the specified maximum number of stages (Nstagemax) had been assigned or taxa whose range maxima fell in the range of the focal taxon with sufficient overlap ran out. When a focal taxon did not have any overlapping taxa to choose from to form the minimum number of stages (Nstagemin), this taxon was disqualified and another taxon was chosen in the same way as the current focal taxon if other choices for the previous focal taxon were available. If it was impossible to find the minimum number of stages for the first focal taxon, it (but not the other ones that had been subsequently considered) was reclassified as a taxon without a stage structure and classified as an invertebrate. This occurred when a focal taxon happened to have a small feeding range so that no range optima fell in the range. The multiple taxa (nodes) selected in this procedure collectively made up one stage‐structured fish taxon and were removed from the pool of available taxa. We then chose another focal taxon with the next highest T2 from the remaining taxa and repeated the steps. We repeated these procedures until the chosen number of fishes had been created or taxa with suitable range overlaps had run out. If the minimum number of stage‐structured taxa could not be created, the food web was discarded. Predation of lower stages by higher stages within a stage‐structured taxon was interpreted as cannibalism. Cannibalism within a stage and cannibalism of higher stages by lower stages (very rare) were removed . Taxa that were not identified as autotrophs nor fishes were identified as invertebrates (nonstructured consumers). Therefore, nodes in the network represented autotrophic trophic species, invertebrate trophic species, or life‐history stages of a fish. Hereafter, a node or a taxon refers to a non‐stage‐structured species (invertebrates and autotrophs) or a fish stage  framework developed by Brose et al.  and expa2.2.1T) in accordance with the theory of allometric predator–prey body mass ratio  of fish predators and their prey to 102.6 and of invertebrate predators and their prey to 101.15  for simplicity . Previous studies that used the ATN framework for aquatic systems , they were removed from preference calculation.We added an ecologically plausible assumption that fishes preferred to feed on fish over invertebrates and on invertebrates over autotrophs, if they were included in their diets, to quickly grow beyond a size vulnerable to predation and for higher fecundity. To achieve these preferences in the absence of such empirical data, we set the parameter hs Table . Similarhs Table . As fishhs Table . Also, bhs Table . Herbivohs Table . If we aq of the functional response was set to 1.5, at the higher end of the values commonly used in previous ATN models (1.2–1.5), to ensure sufficient dynamical stability in large food webs , which implicitly incorporates prey refugia, other evasive behavior, or adaptive foraging  linearly increased with stage, and the terminal stage allocated 20% of surplus energy to reproduction . At the end of each generation, fishes that retained only older stages but not younger ones for more than 10 generations were removed as extinct. This happened in some simulations because the biomasses of older stages without younger ones lingered although they were to decay over time. Each year consisted of 90 time‐steps, representing one growing season, followed by a nongrowing season where reproduction and growth were accounted for. One time‐step corresponded to the generation time of the autotrophic species  for these metrics by taking the differences between the means of resampled values from persisting linked and unlinked food webs.We first assessed various food web properties of the 10,000 networks  to check whether the generated food webs were reasonable. Then, we identified the linked and unlinked food webs that persisted for 1,000 growing seasons  and passed the abovementioned criteria Figure , and retWe checked the sensitivity and robustness of the model outputs to major input parameters Table . We ran 33.1OLmin was reduced to 10%, while the number of fish stages decreased along with other measures as a direct consequence of having fewer fish stages when NStagemin and NStagemax were decreased  as the unlinked webs. Out of 10,000 food webs, 4,315 linked and 2,857 unlinked webs persisted for 1,000 growing seasons and passed the criteria, of which 2,461 webs were shared. Assessed by a set of network structural metrics and characteristics quantified on the unweighted networks after removing extinct taxa , the persisting food webs in both scenarios largely overlapped in terms of the majority of the properties measured Figure . The numThe distributions of measured food web properties between the linked and unlinked food webs overlapped substantially Figure . NonetheNStagemax,NStagemin were smaller (#1), the minimum overlap of niche ranges between consecutive stages of a fish was reduced to 10% (#2), fishes were less energetically efficient (#8), all consumer species and fish stages underwent interference competition (#13), and when q was reduced to 1.2 (#15). The number of persisting webs was markedly smaller  when q = 1.2 (data not shown).Taken together, the results suggested that the life‐history stage structure of fishes on average supported higher diversity in these complex food webs and promoted characteristics that potentially increase the stability of food webs, which may explain the greater number of persisted food webs when fish stages are linked than unlinked. The sensitivity analysis showed that the patterns in the bootstrap differences in mean effect sizes of having a stage structure of fishes remained largely in the same direction (negative or positive) as the baseline simulations across the sensitivity analysis simulations except several cases . Once persisting, food webs with linked life‐history stages were more complex, indicated by the higher numbers of persisting taxa (nodes) and higher link density Figure . The relOur method and the method by Bland et al.  also difThe original niche model by Williams and Martinez  produces4.2How a life‐history structure may affect the stability and persistence of complex food webs has not been much studied. It is not immediately clear whether it is stabilizing or destabilizing based on existing theories. We can expect multiple aspects of stage‐structured populations to contribute to instability. As discussed by Rudolf and Lafferty , when stStages in structured populations can subsidize dwindling stages through growth and reproduction, which is probably one of the main reasons why a stage structure in food webs could enhance the persistence of stage‐structured populations and other dependent populations. Furthermore, biomass flow via growth or reproduction between competing stages with overlapping diet might moderate the destabilization effects of exploitative competition. Stouffer and Bascompte  showed t5Life‐history stages constitute part of biological diversity and increase complexity of food webs. As a large majority of organisms grow in size, often over orders of magnitude, during their lifetime and experience various degrees of ontogenetic diet shifts ; data curation (lead); formal analysis (lead); investigation (lead); methodology (lead); project administration (lead); visualization (lead); writing–original draft (lead); writing–review and editing (lead). Anna Kuparinen: Conceptualization ; formal analysis (supporting); funding acquisition (lead); investigation (supporting); methodology (supporting); project administration (supporting); resources (lead); software (lead); supervision (lead); writing–review and editing (supporting).


To reach 80% adherence to DVANI (Driving and Vehicle Agency Northern Ireland) guidance in acute inpatients ward, T&F HospitalThis is a scale-up of a previous successful QI project on driving and Attention Deficit Hyperactivity Disorder in Belfast Trust. According DVLA's guidance for medical practitioners on the current medical standards of fitness to drive, patients with certain mental health diagnosis are required to inform DVLA of their diagnoses and refrain from driving. Different factors are considered in order to determine patients’ fitness to drive. According to DVLA and GMC, it is medical professionals’ responsibility to advise patients to inform DVLA/DVANI of their mental health diagnosis. It is the patient's legal duty to notify DVLA/DVANI of their diagnosis. Patients can be fined up to £1000 if they failed to inform DVANI of their medical condition.Outcome: Completeness of driving advice given to consecutive patients discharged from T&F hospital from April 2019 to early August 2019 in %Process: Document clearly in electronic and written notes on following - (1) has driving status been asked (2) has patient been advised to inform DVA if required (3) has patient been advised likely how long he/she is to refrain from driving forBalancing: increased the time of reviews, increased numbers of consultant reports requested from DVA4 cycles have been completed. Cycle 1 – baseline and review guidance; Cycle 2 – medical staff education and developed driving advice pathway and patient leaflet; Cycle 3 – admin staff was involved for putting driving advice pathway in admission pack; Cycle 4 – medical staff was educated again regarding importance of documenting electronically. Clear changes were seen after cycle 3 showing an increase of mean of 25% completeness of driving advice to over 90%.It is the legal duty of patients to notify DVANI of mental health diagnosis, however it is the responsibility of medical professionals to advise patients to do so. This QI project has shown improvement in the completeness of driving advice given. Further cycles are to be completed to obtain patient feedback.


Device insertion is a common cardiovascular procedure. Devices are implanted into the right heart, acting as a safeguard against systemic thromboembolism. Lead insertion into the left ventricle is rare, but carries dangerous consequences of thromboembolic events. Diagnosis and intervention of an inadvertently placed lead is essential. This is a case of a defibrillator lead inadvertently inserted into the left cavity, discovered 6 years after implantation. Pacemakers are typically used to restore normal heart rhythm to the heart. While typically found screwed in the right ventricle, pacemaker leads may sometimes travel through the walls of the heart and become lodged in the right ventricle. This complication must be resolved immediately due to the high riskof thromboembolism. With access through the left subclavian, cephalic, axillary, or femoral vein, the latter usually in the setting of a temporary need for device therapy, the ICD leads are placed into the heart and screwed into position in the right ventricle Figure .1 InadInadvertent pacemaker lead placement can be diagnosed using lateral and antero‐posterior (AP) chest X‐rays and further confirmed by a 12‐lead electrocardiogram (ECG) exhibiting a right bundle branch block (RBBB) pattern rather than the expected left bundle branch block (LBBB) appearance on ventricular pacing mode.Diagnosis can occur any time after implantation and approaches differ depending on patient clinical status and time of displacement. In early displacement, revision with repositioning of the lead is possible because the lead has not yet been fixed in the heart. However, with late displacements, repositioning carries unknown and unnecessary risks.2A 76‐year‐old man with history of ischemic cardiomyopathy and paroxysmal atrial fibrillation who underwent a Dual‐Chamber Medtronic Implantable Cardioverter‐Defibrillator (ICD) placement 6 years earlier in an outside facility presented to the emergency room with worsening shortness of breath. Initial workup in the emergency room revealed acute on chronic combined congestive heart failure. An AP chest X‐ray film was interpreted by the radiologist as cardiomegaly with pulmonary vascular congestion and satisfactory ICD lead position Figure . No lateBedside Echo showed severely reduced left ventricular systolic function with dilated right ventricle and moderate‐to‐severe pulmonary hypertension. Surprisingly, the ICD lead was clearly going from the left atrium through the mitral valve to the left ventricular cavity Figures , and 5. Because extraction of a chronically implanted ICD lead carries a high risk of major cardiovascular complications (2%‐4%) including vascular injury, cardiac perforation resulting in cardiac tamponade, and occasionally thromboembolic complications or even death, and because the patient was chronically anticoagulated, the decision is made to continue conservative management.3Implantation of a pacemaker or defibrillator is a common procedure to treat heart rate and rhythm abnormalities. Single lead ICDs are used to prevent sudden cardiac death in patients at high risk of life‐threatening cardiac arrhythmia by sensing and then delivering electric shock to restore normal cardiac rhythm. They are typically placed in the right ventricular cavity. However, 27% of all complications from ICD insertions are due to lead dislodgment or unsatisfactory position.Diagnosis of a misplaced lead in the left ventricle requires high index of suspicion and immediate action. A misplaced lead in the left ventricle creates an RBBB‐pattern on an ECG and is often the most important tool in diagnosis.Management of an inadvertent left ventricle lead depends heavily on time after implantation. Early detection of a misplaced lead allows for lead extraction, reducing the risk for TE events and avoiding the need for lifelong anticoagulation.4Inadvertent pacemaker or defibrillator lead placement can lead to serious and occasionally life‐threatening complications and can be overlooked for a long period of time. Very careful interpretation of the ECG and device data “Pacing threshold, sensing and impedance” in addition to appropriate use of the available imaging modalities can lead to early diagnosis and treatment and can save the patient from such serious complications.The authors declare no conflicts of interest.AA: analyzed and studied patient complaints, images, and eventual diagnosis, as well as reviewed all drafts of the article. AO: wrote main manuscript and critically reviewed all drafts.Written with consent of the patient.


Finally, we examined whether trait covariance strength at fledging was related to postfledging survival. We found that higher nest predation risk was correlated with faster skeletal growth and that our proxies for growth corresponded with increased trait covariance strength (rp), which subsequently, correlated with higher mortality in the next life stage (postfledging period). These results provide an indication that extrinsic pressures (nest predation) impact rates of growth, and that there are costs of rapid growth across species, expressed as higher mean rp and elevated postfledging mortality. The link between higher levels of trait covariance at fledging and increased mortality is unclear, but increased trait covariance strength may reflect reduced phenotypic flexibility , which may limit an organism's capacity for coping with environmental or ecological variability.Life history studies have established that trade‐offs between growth and survival are common both within and among species. Identifying the factor(s) that mediate this trade‐off has proven difficult, however, especially at the among‐species level. In this study, we examined a series of potentially interrelated traits in a community of temperate‐zone passerine birds to help understand the putative causes and consequences of variation in early‐life growth among species. First, we examined whether nest predation risk (a proven driver of interspecific variation in growth and development rates) was correlated with species‐level patterns of incubation duration and nestling period length. We then assessed whether proxies for growth rate covaried with mean trait covariance strength , and that higher levels of trait covariance result in elevated rates of mortality. These growth rates are shaped by the trade‐offs between extrinsic pressures and a suite of intrinsic costs and constraints associated with fast growth Arendt,  Figure . Rapid grp). Phenotypic trait covariance indicates how correlated two traits are among individuals. For instance, if values for two traits are plotted against one another , points may be expected to tightly covary  or may only be loosely correlated . Phenotypic trait covariance strength has proven to be a powerful tool for uncovering costs associated with developmental stress , for example, documented that stress during development resulted in near‐universal increases in trait covariance strength for a broad range of physiological and morphological traits  egg incubation duration and nestling duration, and (B) interspecific patterns of growth?rp) among morphological traits?Are interspecific patterns of growth associated with prefledging trait covariance strength . To document nest life‐history traits such as incubation and nestling period length, and determine nest fate (fledge/fail), we checked nests every 3 to 6 days (average 3) during the incubation period and much of the nestling period, and every 1 to 2 days as the predicted date of fledging approached. We assumed nest failure/predation when all contents of the nest (eggs/nestlings) disappeared before the predicted day of fledging and we did not observe adults feeding fledglings.Spizella pusilla) is at a different developmental stage on Day 7 compared to an Eastern Bluebird . We therefore determined that assigning a life stage (fledging) as the reference point was most useful. Indeed, the factors that affect growth and development of juveniles up to the point of fledging can have important carryover effects on subsequent survival during the postfledging period , recorded wing length (± 0.5 mm) and tarsus length (± 0.01 mm), and banded them with a U.S. Geological Survey metal band. All juveniles in this study were banded and sampled by the same researcher. We assessed trait covariance at fledging rather than an arbitrary day posthatch , as a way to standardize sampling across all the study species. For example, a Field Sparrow , or the number of days from incubation initiation to fledge (postlay growth). The duration of egg incubation may better standardize the developmental starting point from the fertilized gamete. It is important to note that we use these temporal variables, and size‐adjusted measures for growth because birds were only measured once. As such, our measures serve as proxies for traditional estimates derived from growth curves with multiple measures per individual. However, we believe that the duration of both incubation period and the nestling period should provide meaningful information on rates of growth and development during those respective periods. Incubation duration should provide a proxy for embryonic growth rate  where 1 to 3 individuals were tagged per brood as part of another study; Jones et al., For nine of our 21 focal species ) for each species  using the logistic exposure method Shaffer,  in SAS. We used multi‐state models in program MARK (White and Burnham rp) for each trait‐by‐trait comparison. For each species, we then calculated the average rp across the three associations as an overall measure of trait covariance strength. Of the nestlings measured (Table and mass × wing length associations). Including these values in the analyses did not impact results qualitatively, but these individuals or individual traits had a disproportionate effect on correlation coefficient values relative to all other individuals of the same species. Importantly, we note that our correlations are not confounded by potential differences in the stage of growth  for each trait, as in all species juveniles had fully grown tarsi but had yet to reach adult levels of mass and wing length.We examined associations between three morphological traits: mass, wing length, and tarsus length. For one species (dickcissels), wing length was not recorded from 2014 to 2015, limiting associations in those years to between mass and tarsus length. To assess the phenotypic correlations, we calculated the phenotypic correlation coefficient (We tested if nest predation pressure (as defined by DMR) was linked to interspecific rates of growth. We did this by first examining the associations between nest DMR and the time available for growth (incubation duration and nestling duration), and then, we examined the associations between nest DMR and growth rates. We focused on structural growth (tarsus length) for this analysis because mass and wing length can change after fledging  corresponded with th Table . We inclrp at fledging was linked to cumulative PFM rates using a linear regression with cumulative PFM rate as the independent variable and mean rp as the dependent variable. We ran the model with rp generated from all nestlings for the ten species we had postfledging data for, as well as from just the individuals we had postfledging data for; we excluded the Eastern Phoebe from the latter due to low sample sizes. To better understand the sources of postfledging mortality , and whether this was important in influencing the relationship between rp at fledging and postfledging mortality, we partitioned postfledging mortality into “predator‐induced” and “non‐predator‐induced” sources, and compared the associations between species‐level mean trait covariance and both subsets of postfledging mortality, as well as cumulative postfledging mortality using an AICc model comparison approach.Additionally, we tested whether species‐level For all models, we examined diagnostic plots to confirm that residuals approximated a normal distribution and met the assumption of homogeneous variances. In comparative methods, phylogenetic corrections are commonly used to control for perceived lack of statistical independence among species . We also found positive associations between trait covariance and postfledging mortality—for the nine species in which we tagged nestlings—for trait covariance values generated from all nestlings measured . Species that exhibit more rapid rates of growth presumably have evolved mechanisms to mitigate the physiological costs of fast growth , species under higher nest predation risk may have been forced to reduce their incubation and nestling periods and accelerate growth  and nestling both undergo growth and development, but the posthatch level of growth far exceeds that which occurs in the egg  nestlings prior to fledging  suggests that trait associations are themselves indicative of processes that impact an organism's survival.Previous work on postfledging mortality indicates that wing development/growth may be associated with postfledging mortality at both the intraspecific and interspecific levels  suggests a high cost. If rapid growth leads to more canalized development, organisms that grow rapidly may have reduced capacity for dealing with future challenges due to lost phenotypic flexibility, which may manifest in lower survival during subsequent juvenile and adult life stages ; Data curation (supporting); Formal analysis (lead); Writing‐original draft (lead); Writing‐review & editing . Todd M. Jones: Conceptualization (supporting); Data curation (lead); Formal analysis (supporting); Funding acquisition (lead); Writing‐original draft (supporting); Writing‐review & editing . Jeffrey D. Brawn: Conceptualization (supporting); Data curation (supporting); Funding acquisition (supporting); Writing‐original draft (supporting); Writing‐review & editing . Michael P. Ward: Conceptualization (supporting); Data curation (supporting); Funding acquisition (lead); Writing‐original draft (supporting); Writing‐review & editing .