Jasechko et al. reply.

replying to A. M. J. Coenders-Gerrits et al. 506, http://dx.doi.org/10.1038/nature12925 (2014)In their Comment, Coenders-Gerrits et al. suggest that our conclusion that transpiration dominates the terrestrial water cycle is biased by unrepresentative input data and optimistic uncertainty ranges related to runoff, interception and the isotopic compositions of transpired and evaporated moisture. We clearly presented the uncertainties applied in our Monte-Carlo sensitivity analysis, we reported percentile ranges of results rather than standard deviations to best communicate the nonlinear nature of the isotopic evaporation model, and we highlighted that the uncertainty in our calculation remains large, particularly in humid catchments (for example, figure 2 in our paper).

Terrestrial water fluxes dominated by transpiration.

Renewable fresh water over continents has input from precipitation and losses to the atmosphere through evaporation and transpiration. Global-scale estimates of transpiration from climate models are poorly constrained owing to large uncertainties in stomatal conductance and the lack of catchment-scale measurements required for model calibration, resulting in a range of predictions spanning 20 to 65 per cent of total terrestrial evapotranspiration (14,000 to 41,000 km(3) per year) (refs 1, 2, 3, 4, 5). Here we use the distinct isotope effects of transpiration and evaporation to show that transpiration is by far the largest water flux from Earth's continents, representing 80 to 90 per cent of terrestrial evapotranspiration. On the basis of our analysis of a global data set of large lakes and rivers, we conclude that transpiration recycles 62,000 ± 8,000 km(3) of water per year to the atmosphere, using half of all solar energy absorbed by land surfaces in the process. We also calculate CO2 uptake by terrestrial vegetation by connecting transpiration losses to carbon assimilation using water-use efficiency ratios of plants, and show the global gross primary productivity to be 129 ± 32 gigatonnes of carbon per year, which agrees, within the uncertainty, with previous estimates. The dominance of transpiration water fluxes in continental evapotranspiration suggests that, from the point of view of water resource forecasting, climate model development should prioritize improvements in simulations of biological fluxes rather than physical (evaporation) fluxes.

The use of VV-ECMO in patients with drug dependencies.

The purpose of this study is to determine the effect of illicit drug and alcohol dependencies on mortality, length of stay, and complications in patients who have been supported with veno-venous extracorporeal membrane oxygenation (VV-ECMO) following respiratory failure not responsive to conventional methods of ventilation. 584 VV-ECMO referrals received at Wythenshawe Hospital were reviewed for evidence of drug dependency. 13 patients were identified as being drug-dependent and having undergone treatment with VV-ECMO. A matched cohort of 13 non-drug-dependent patients was identified using date of birth, pre-ECMO Murray Score, and primary diagnosis. The outcomes were compared. 19 more complications were found amongst the drug-dependent patients compared with the non-drug-dependent cohort (39 vs 20). A mean difference of 1.46 complications per patient was calculated (p = 0.005). Mortality after 180 days was reported in 4 of the drug-dependent patients, compared with one in the matched cohort. Length of stay on ECMO was increased on average by 1.93 days amongst the drug-dependent patients (p = 0.557); however, the sample size was not great enough to achieve statistical significance. Patients with drug dependencies undergoing VV-ECMO have more complications when compared with a cohort of patients with no proven or suspected drug dependencies. Differences in morbidity and mortality were not statistically significant.

Extended megadroughts in the southwestern United States during Pleistocene interglacials.

The potential for increased drought frequency and severity linked to anthropogenic climate change in the semi-arid regions of the southwestern United States (US) is a serious concern. Multi-year droughts during the instrumental period and decadal-length droughts of the past two millennia were shorter and climatically different from the future permanent, 'dust-bowl-like' megadrought conditions, lasting decades to a century, that are predicted as a consequence of warming. So far, it has been unclear whether or not such megadroughts occurred in the southwestern US, and, if so, with what regularity and intensity. Here we show that periods of aridity lasting centuries to millennia occurred in the southwestern US during mid-Pleistocene interglacials. Using molecular palaeotemperature proxies to reconstruct the mean annual temperature (MAT) in mid-Pleistocene lacustrine sediment from the Valles Caldera, New Mexico, we found that the driest conditions occurred during the warmest phases of interglacials, when the MAT was comparable to or higher than the modern MAT. A collapse of drought-tolerant C(4) plant communities during these warm, dry intervals indicates a significant reduction in summer precipitation, possibly in response to a poleward migration of the subtropical dry zone. Three MAT cycles ∼2 °C in amplitude occurred within Marine Isotope Stage (MIS) 11 and seem to correspond to the muted precessional cycles within this interglacial. In comparison with MIS 11, MIS 13 experienced higher precessional-cycle amplitudes, larger variations in MAT (4-6 °C) and a longer period of extended warmth, suggesting that local insolation variations were important to interglacial climatic variability in the southwestern US. Comparison of the early MIS 11 climate record with the Holocene record shows many similarities and implies that, in the absence of anthropogenic forcing, the region should be entering a cooler and wetter phase.

Sensory neuronopathy in patients harbouring recessive polymerase γ mutations.

Defects in the mitochondrial DNA replication enzyme, polymerase γ, are an important cause of mitochondrial disease with ∼25% of all adult diagnoses attributed to mutations in the POLG gene. Peripheral neuronopathy is often part of the clinical syndrome and can represent the most disabling feature. In spite of this, the molecular mechanisms underlying the neuronopathy remain to be elucidated and treatment strategies are limited. In the present study, we use a combined approach comprising clinical, electrophysiological, neuropathological and molecular genetic investigations to unravel the mechanisms underpinning peripheral neuronopathy in autosomal recessive polymerase γ-related disease. Electrophysiological assessments documented a dorsal root ganglionopathy in all 11 cases. Of the 11 cases, eight also showed changes consistent with motor fibre loss. Detailed neuropathological investigation of two patients confirmed the electrophysiological findings, revealing atrophy of posterior columns and striking neuronal cell loss from the dorsal root ganglia, which was accompanied by severe mitochondrial biochemical abnormalities involving respiratory chain complexes I and IV due to clonally-expanded mitochondrial DNA deletions and a significant reduction in mitochondrial DNA copy number in affected neurons. We propose that the respiratory chain defects, secondary to mitochondrial DNA deletion and depletion, are likely to be responsible for pathology observed in the dorsal root ganglion and the sensory ganglionopathy documented electrophysiologically.

Variation in the neurophysiological examination of amyotrophic lateral sclerosis in Europe.

Our objective was to analyse how patients with amyotrophic lateral sclerosis (ALS) are examined neurophysiologically at different European centres in order to identify possible areas with variation or disagreement in the neurophysiological examination of ALS. Ninety-three prospectively collected examinations from six out of seven neurophysiologists in the European ESTEEM project were analysed. All examinations were peer reviewed with an electromyographic consensus diagnosis of motor neuron disease and the diagnosis of ALS confirmed by clinical follow-up. The examinations were analysed for differences among the physicians in EMG techniques and number and distribution of examined and abnormal muscles and nerve segments. Considerable variation was found among the physicians regarding the average numbers of performed and abnormal EMG and nerve conduction studies per patient, the EMG techniques used, and the topographical distribution of the examined muscles. The existence of two different examination approaches, one with quantitative EMG analyses and relatively few muscles studied, and one with more muscles studied using qualitative methods was clearly confirmed in the present study. The large variation among the physicians indicates that different criteria were used, or that criteria were used inconsistently.

A prospective multicentre study on sural nerve action potentials in ALS.

OBJECTIVE: To evaluate sensory nerve conduction studies in ALS in a prospective multicentre study involving 7 neurophysiologists from 6 European countries. METHODS: Bilateral sural potentials were obtained in 35 ALS patients and 35 age-matched controls according to a standardised examination protocol using antidromic surface technique. The recordings from the right sural nerve of the controls were used for reference values. A reduction from the mean of controls greater than 2 SDs was considered abnormal. RESULTS: Reduced sensory nerve action potential (SNAP) amplitude or reduced conduction velocity (CV), or both, was found in 6 ALS patients (17%). Decrease in CV was the most frequent finding, and was observed in 8 nerves from 5 patients. Reduced SNAP amplitude was found in 2 nerves from 2 patients. All changes were minor ranging from -2.1 to -3.2 SDs. CONCLUSIONS: This is the first standardised multicentre study on sensory potentials in ALS. It confirms that although normal sensory findings should be expected in the majority of ALS patients, minor abnormalities are not uncommon. SIGNIFICANCE: Mild sensory abnormalities do not necessarily exclude a diagnosis of ALS.

Extracorporeal membrane oxygenation in severe respiratory failure resulting from burns and smoke inhalation injury.

Extracorporeal membrane oxygenation (ECMO) is one of the most frequent forms of extracorporeal life support (ECLS) and can be used as rescue therapy in patients with severe respiratory failure resulting from burns and/or smoke inhalation injury. Experience and literature on this treatment option is still very limited, consequently results are varied. We report a retrospective analysis of our experience with veno-venous (VV) ECMO in burn patients. All five patients, three male and two female (age: 28-37 years) had flame type burns and smoke inhalation injury. Their Murray scores ranged between 3.25 and 3.75, and their revised Baux scores between 62 and 102. The mean pre-ECMO conventional ventilation time was 7.4days (3-13). The mean ECMO duration was 18days (8-35). Three patients were cannulated with dual lumen, two with separate cannulae. One oxygenator had to be changed due to technical issues and two patients needed two parallel oxygenators. Four patients had renal replacement therapy. All patients needed vasoconstrictor support, antibiotics and packed red blood cells (5-62 units). Three had steroid treatment. All five patients were successfully weaned from ECMO. One patient died later from multi-organ failure in the ICU, the other four patients survived. VV-ECMO is a useful rescue intervention in patients with burns related severe respiratory failure. Patients in our institution benefit from having both burns and ECMO centres with major expertise in the field under one roof. The results from this small cohort are encouraging, although more cases are needed to draw more robust conclusions.

Influence of peer review medical audit on pathophysiological interpretation of nerve conduction studies in polyneuropathies.

OBJECTIVE: To evaluate the possible influence of peer review medical audit on experienced physicians' pathophysiological interpretation of nerve conduction studies in polyneuropathy patients. METHODS: Since 1992, 7 European neurophysiologists have collected samples of their patient examinations for regular review where the physicians interpret each other's cases electronically and subsequently discuss them at regular workshop meetings (i.e. a form of medical audit). Two sets of 100 polyneuropathy examinations interpreted with an interval of 4-6 years were selected. The sets contained 1456 and 1719 nerve conduction studies, each given a pathophysiological test conclusion by each individual physician. Inter-physician agreement on interpretation of demyelination and axonal loss of the nerve, as well as neuropathic and unspecific findings, was estimated using kappa statistics. RESULTS: Increased agreement from set 1 to set 2 was found on interpretation of demyelination of the nerve (set 1: kappa=0.22; set 2: kappa=0.45), and of neuropathic (set 1: kappa=0.46; set 2: kappa=0.64) and unspecific findings (set 1: kappa=0.35; set 2: kappa=0.54). No changes were found on interpretation of axonal loss (set 1: kappa=0.26; set 2: kappa=0.31) and normal findings (set 1 and set 2: kappa=0.90). CONCLUSIONS: Participation in regular peer review medical audit resulted in increased agreement on interpretation of nerve conduction studies for 6 of the 7 participants. The study further highlights the need for better definition of criteria for identification of demyelinating, and in particular, axonal peripheral neuropathies. SIGNIFICANCE: International collaboration involving peer review medical audit may contribute to development of practice guidelines and, in turn, to increased quality of electrodiagnostic medicine.

Influence of medical audit on electrodiagnostic evaluation of polyneuropathy. A multicentre study.

OBJECTIVE: Since 1992, 7 European neurophysiologists have participated in the ESTEEM project concerned with improvements in electrodiagnostic medicine. This study assesses whether the collaboration that includes peer review medical audit has influenced the involved physicians' electrodiagnostic criteria for polyneuropathy (PNP) diagnosing and classification. METHODS: Two sets of each physician's PNP examinations performed early and late in the study were examined for changes in (1) number of studies with abnormal electrophysiological findings required for diagnosing PNP, and (2) agreement between the classifications given by the individual physicians and the peer review group. RESULTS: The average number of abnormal motor nerve segments per patient increased from 4.6 to 6.4 during the study. Although most individual changes were minor, the second set of examinations showed an increased homogeneity among the physicians in the number of abnormal motor nerve segments and abnormal F wave studies, and a tendency towards increased homogeneity in the number of abnormal sensory nerve segments. There was also an increased agreement on pathophysiological PNP classification in the second set of examinations compared to the first set. CONCLUSIONS: The participation in the ESTEEM project seems to have impacted the physicians' clinical routine, possibly as they have accustomed themselves to apply criteria more strictly. SIGNIFICANCE: This study support that international collaboration is a useful step towards improvements in electrodiagnostic medicine.

Pathophysiology inferred from electrodiagnostic nerve tests and classification of polyneuropathies. Suggested guidelines.

OBJECTIVE: To present criteria for pathophysiological interpretation of motor and sensory nerve conduction studies and for pathophysiological classification of polyneuropathies suggested by a group of European neurophysiologists. METHODS: Since 1992 seven neurophysiologists from six European countries have collected random samples of their electrodiagnostic examinations for peer review medical audit in the ESTEEM (European Standardized Telematic tool to Evaluate Electrodiagnostic Methods) project. Based on existing criteria in the literature, the experience with a patient material of 572 peer reviewed electrodiagnostic examinations, and productive discussions between the physicians at workshops, the collaboration has produced a set of criteria now routinely used at the centres involved in the project. RESULTS: The first part of the paper considers pathophysiology of individual nerve segments. For interpretation of motor and sensory nerve conduction studies, figures showing change in amplitude versus change in conduction velocity/distal latency and change in F-wave frequency versus change in F-wave latency are presented. The suggested boundaries delimit areas corresponding to normal, axonal, demyelinated, or neuropathic nerve segments. Criteria for motor conduction block in upper and lower extremities are schematically depicted using the parameters CMAP amplitude and CMAP duration. The second part of the paper suggests criteria for classification of polyneuropathies into axonal, demyelinating, or mixed using the above-mentioned criteria. CONCLUSIONS: The suggested criteria are developed during many years of collaboration of different centres and may be useful for standardization in clinical neurophysiology. SIGNIFICANCE: Consistent interpretation of nerve conduction studies is an important step in optimising diagnosis and treatment of nerve disorders.

Impact of medical audit on electrodiagnostic medicine in polyneuropathy.

OBJECTIVE: The aim of the study was to investigate whether experienced physicians' electrodiagnostic practice and criteria can be influenced by international collaboration involving peer review medical audit. METHODS: Data was obtained from the ESTEEM project, an ongoing collaboration since 1991 among European neurophysiologists concerned with quality improvement in electrodiagnostic medicine. Three sets of the physicians' polyneuropathy examinations performed with intervals of 2-4 years were analysed. RESULTS: Changes towards increased homogeneity among the physicians were found in (1) the average number of studies performed per patient and the number of abnormal studies required for accepting the diagnosis of polyneuropathy, with the most pronounced changes seen for abnormal motor nerve segments, abnormal F-wave studies, and electromyographic studies, and (2) the agreement on pathophysiological interpretation of nerve conduction studies and classification of polyneuropathy. CONCLUSIONS: Changes towards increased homogeneity contributed to years of participation in peer review medical audit, were seen among a group of experienced physicians. Peer review medical audit as carried out here is however difficult to scale up. Therefore guidelines or minimal criteria should ideally supplement a medical audit process to disseminate the results obtained to a larger audience. SIGNIFICANCE: These results support the role of international peer review medical audit in quality improvement of electrodiagnostic medicine.

Dok-7 mutations underlie a neuromuscular junction synaptopathy.

Congenital myasthenic syndromes (CMSs) are a group of inherited disorders of neuromuscular transmission characterized by fatigable muscle weakness. One major subgroup of patients shows a characteristic "limb girdle" pattern of muscle weakness, in which the muscles have small, simplified neuromuscular junctions but normal acetylcholine receptor and acetylcholinesterase function. We showed that recessive inheritance of mutations in Dok-7, which result in a defective structure of the neuromuscular junction, is a cause of CMS with proximal muscle weakness.

Macroelectromyography: a review of the technique and its value in the investigation of neuromuscular disorders.

The background for the macroelectromyography technique, which was developed by Erik Stålberg to measure the size of motor unit potentials in human muscles, is reviewed. The method employs a modified single-fiber electrode with a large nonselective recording surface capable of recording the activity from all the fibers of a motor unit. The findings in normal subjects and its application in the study of motor unit recruitment are described. The value of the technique in the investigation, diagnosis, and monitoring of various neuromuscular diseases, including primary myopathies and neurogenic conditions, is discussed.

Normokalemic periodic paralysis revisited: does it exist?

Normokalemic periodic paralysis (normoKPP) is well established in the literature, but there are doubts as to whether it exists as a discrete entity. Retrospective clinical and molecular analysis has confirmed suspicions that most normoKPP families actually have a variant of hyperkalemic periodic paralysis (hyperKPP) due to a mutation of the muscle-specific sodium channel gene (SCN4A). However, the original normoKPP family described by Poskanzer and Kerr (Poskanzer DC, Kerr DNS. A third type of periodic paralysis, with normokalemia and favourable response to sodium chloride. Am J Med 1961;31:328-342) has remained unchallenged. We identified the Met1592Val mutation of SCN4A in an affected descendent of this original normoKPP family. This is the final piece in the puzzle: normoKPP is actually a variant of hyperKPP and is not a distinct disorder.