Tbx2 is a master regulator of inner versus outer hair cell differentiation.

The cochlea uses two types of mechanosensory cell to detect sounds. A single row of inner hair cells (IHCs) synapse onto neurons to transmit sensory information to the brain, and three rows of outer hair cells (OHCs) selectively amplify auditory inputs1. So far, two transcription factors have been implicated in the specific differentiation of OHCs, whereas, to our knowledge, none has been identified in the differentiation of IHCs2-4. One such transcription factor for OHCs, INSM1, acts during a crucial embryonic period to consolidate the OHC fate, preventing OHCs from transdifferentiating into IHCs2. In the absence of INSM1, embryonic OHCs misexpress a core set of IHC-specific genes, which we predict are involved in IHC differentiation. Here we find that one of these genes, Tbx2, is a master regulator of IHC versus OHC differentiation in mice. Ablation of Tbx2 in embryonic IHCs results in their development as OHCs, expressing early OHC markers such as Insm1 and eventually becoming completely mature OHCs in the position of IHCs. Furthermore, Tbx2 is epistatic to Insm1: in the absence of both genes, cochleae generate only OHCs, which suggests that TBX2 is necessary for the abnormal transdifferentiation of INSM1-deficient OHCs into IHCs, as well as for normal IHC differentiation. Ablation of Tbx2 in postnatal, largely differentiated IHCs makes them transdifferentiate directly into OHCs, replacing IHC features with those of mature and not embryonic OHCs. Finally, ectopic expression of Tbx2 in OHCs results in their transdifferentiation into IHCs. Hence, Tbx2 is both necessary and sufficient to make IHCs distinct from OHCs and maintain this difference throughout development.

Intrahepatic Cholangiolitis in Cystic Fibrosis (ICCF): An Under-Appreciated Cause of Persistent Cholestasis in Infancy.

Liver histology in infants with cystic fibrosis (CF) and persistent cholestasis is seldom reported in detail. We extend previous observation of a distinctive intrahepatic cholangiopathy (ICCF) to 3 additional infants homozygous for CFTR pathological variants and a fourth infant with a heterozygous CFTR variant, summarizing our experience in 10 infants with CFTR variants and persistent cholestasis. Cholangiograms demonstrate abnormal extrahepatic ducts in 2 infants with CF, 1 with uniform dilatation interpreted as a choledochal cyst and the other with narrow patent ducts. Liver histology in 3 CF homozygotes had prominent ductular reaction with a focally destructive cholangiolitis (inflammation of small bile ducts). The CFTR heterozygote had generalized portal edema with ductular reaction and paucity but no cholangitis. Cholestasis slowly subsided in all infants. ICCF is characterized by severe ductular reaction, prominent cholangiocyte injury, and multifocal necrotizing cholangiolitis. Local aggregates of portal ceroid might suggest previous bile leakage from damaged ducts. ICCF in liver biopsies from infants with cystic fibrosis and persistent cholestasis is unrelated to the specific CFTR genotype. Liver biopsy findings and intraoperative cholangiogram help rule out biliary atresia. ICCF is an early manifestation of CF, a likely prototype for pathogenesis of cystic fibrosis liver disease later in life.

Vasospasm and subsequent stroke from paraneoplastic syndrome in a pediatric patient with an intracranial mature teratoma: a case report.

Teratomas account for 18-20% of all intracranial germ cell tumors and mostly occur in the pineal region with only a few cases of pediatric sellar and suprasellar teratomas described in the literature. Here, we present a case of a child with an intracranial mature teratoma with pancreatic features causing vasospasm and subsequent stroke, found to be positive for CDKN2A-an independent variant associated with malignancy and small vessel disease leading to stroke.

Resonant Fragmentation of the Water Cation by Electron Impact: a Wave-Packet Study.

We have investigated the dissociation of a resonant state that can be formed in low energy electron scattering from H2 O+ . We have chosen the second triplet resonance above the B ˜ 2 A ' ${{{\tilde{\rm {B}}}}\;^2 {\rm{A{^\prime}}}}$ ( B ˜ 2 B 2 ) ${{\rm{(\tilde{B}}}\;^2 {\rm{B}}_2 )}$ state of H2 O+ whose autoionization mainly produces H2 O+ ( X ˜ 2 A ' ' ${{{\tilde{\rm {X}}}}\;^2 {\rm{A{^\prime}{^\prime}}}}$ ). We have considered both dissociation of the resonant state itself, dissociative recombination (DR), or the dissociation of the H2 O+ cation after autodetachment, dissociative excitation (DE). The time-evolution of a wave packet on the potential energy surfaces of the resonance and cationic states shows, for the initial conditions studied, that the probability for DR is about 38 % while the probability for DE is negligible.

Basiliximab therapy for immune-mediated bowel disease in a pediatric heart transplant patient.

In pediatric patients who undergo heart transplantation, severe immune-mediated bowel disease has been reported. Management is complex, and there are little data discussing the use of basiliximab for immune-mediated bowel disease. This case report discusses a pediatric patient who developed immune-mediated bowel disease following heart transplantation and was successfully managed with basiliximab.

Relationship between trabecular bone score, bone mineral density and vertebral fractures in patients with axial spondyloarthritis.

BACKGROUND: In patients with axial spondyloarthritis, vertebral fracture risk is elevated and not always correlated with bone mineral density (BMD). Trabecular bone score (TBS) may offer some advantages in the assessment of vertebral fracture risk in these patients. The primary objective of this study was to compare TBS and BMD between axial spondyloarthritis patients depending on their vertebral fracture status. Secondary objectives were to estimate the prevalence of morphometric vertebral fractures, and to explore factors associated with fracture, as well as the interference of syndesmophytes on BMD and TBS. METHODS: A cross-sectional study was conducted. Data were collected on demographic and clinical characteristics, lab results, imaging findings and treatment. Statistical analysis was performed using SPSS v.13 statistical software. RESULTS: Eighty-four patients (60 men and 24 women; mean age of 59 years) were included. Nearly half (47.6%) of them had lumbar syndesmophytes. The rate of morphometric fracture was 11.9%. TBS showed a higher area under the curve (0.89) than total hip, femoral neck and lumbar BMD (0.80, 0.78, and 0.70 respectively) for classifying patients regarding their fracture status. Nonetheless, the differences did not reach statistical significance. Syndesmophytes affected lumbar spine BMD (p < 0.001), but not hip BMD or TBS. Fractures were associated with TBS, total hip BMD, erythrocyte sedimentation rate and C-reactive protein levels. CONCLUSIONS: We identified decreased TBS and total hip BMD, as well as increased erythrocyte sedimentation rate and C-reactive protein levels as factors associated with morphometric vertebral fractures. Unlike lumbar spine BMD, TBS is not affected by the presence of syndesmophytes.

Differential Immunoexpression of BRAF/V600E, Senescence Markers, PTEN, and T-type Calcium Channels in Acquired Naevi According to their Histopathological and Dermoscopic Classification.

BRAF/V600E mutation and other cell growth/growth-control mechanisms are involved in naevogenesis and melanomagenesis. Immunoexpression of BRAF/V600E and other molecules (p16, phosphatase and tensin homologue (PTEN), Ki67, hTERT and Cav3.1 and 3.2 calcium channels) were investigated in 80 histopatho-logically and dermoscopically classified acquired naevi. Regarding BRAF/V600E, dysplastic naevi showed lower immunostaining than common naevi, which was significant in comparison with intradermal naevi, which showed the highest BRAF/V600E histoscore. Junctional naevi showed the lowest BRAF/V600E levels. Globular/cobblestone and reticular dermoscopic patterns were consistently associated with high and low BRAF/V600E immunoexpression, respectively, but Zalaudek's peripheral globule pattern (CR/PG) showed the highest BRAF/V600E immunoexpression. Among global patterns, the previously not investigated multicomponent pattern showed the lowest BRAF/V600E immunoexpression. Regarding the remaining biomarkers, new immunohistochemical features were found, in particular p16 and PTEN low expression in multicomponent pattern; and Ki67, hTERT and Cav.3.1 high expression in CR/PG. In conclusion, histopathology and dermoscopy provide complementary information regarding the biology of melanocytic naevi.

Imaging of the Lactate/Pyruvate Ratio Using a Genetically Encoded Förster Resonance Energy Transfer Indicator.

The ratio between the cytosolic concentrations of lactate and pyruvate is a direct readout of the balance between glycolysis and mitochondrial oxidative metabolism. Current approaches do not allow detection of the lactate/pyruvate ratio in a single readout with high spatial/temporal resolution in living systems. Using a Förster resonance energy transfer (FRET)-based screening strategy, we found that the orphan transcriptional factor LutR from Bacillus licheniformis is an endogenous sensor of the lactate/pyruvate ratio, suitable for use as a binding moiety to develop a lactate/pyruvate ratio FRET-based genetically encoded indicator, Lapronic. The sensitivity of the indicator to lactate and pyruvate was characterized through changes in the fluorescence FRET ratio and validated with isothermal titration calorimetry. Lapronic was insensitive to physiological pH and temperature and did not respond to structurally related molecules acetate and ß-hydroxybutyrate or cofactors NAD+ and NADH. Lapronic was expressed in HEK 293 cells showing a homogeneous cytosolic localization and was also targeted to the mitochondrial matrix. A calibration protocol was designed to quantitatively assess the lactate/pyruvate ratio in intact mammalian cells. Purified protein from Escherichia coli showed robust stability over time and was found suitable for lactate/pyruvate ratio detection in biological samples. We envision that Lapronic will be of practical interest for basic and applied research.

Urine exosomal ceruloplasmin: a potential early biomarker of underlying kidney disease.

BACKGROUND: Previously we found that kidney tissue and urinary exosomes from patients of diabetic kidney disease showed high levels of ceruloplasmin (CP). Because CP is an acute-phase protein of kidney origin, it could be an early marker of many other kidney diseases. To investigate this hypothesis, we first measured urine exosomal and kidney expression of CP in non-diabetic chronic kidney disease (CKD) patients (membranous nephropathy, focal segmental glomerulosclerosis, lupus nephritis and IgA nephropathy) followed by a longitudinal study in rat passive Heymann nephritis (PHN), a model of human membranous nephropathy. METHODS: Urinary exosomes were isolated from urine of patients (and rats) by differential centrifugation. The exosomal extracts were used for measuring CP using ELISA. Kidney expression of CP was evaluated by immune-staining biopsy tissues. Similar techniques were applied in rat PHN model (produced by injection of anti-gp600 antiserum) to analyze urine exosomal and kidney CP. RESULTS: Urine exosomal CP levels were 10-20 times higher in CKD patients than in controls; consistent with this we found high immune-reactive CP localized in tubules and collecting ducts of biopsies of CKD patients. In the PHN model urinary exosomal CP level was significantly higher prior to the onset of proteinuria. Early rise of urine exosomal CP, which preceded proteinuria, correlated with high immunoreactive CP found in rat kidneys at this time. CONCLUSION: We propose that urine exosomal CP, observed to increase prior to proteinuria, makes it a potential urinary biomarker to diagnose early kidney disease.

Majorization and Dynamics of Continuous Distributions.

In this work we show how the concept of majorization in continuous distributions can be employed to characterize mixing, diffusive, and quantum dynamics along with the H-Boltzmann theorem. The key point lies in that the definition of majorization allows choosing a wide range of convex functions ϕ for studying a given dynamics. By choosing appropriate convex functions, mixing dynamics, generalized Fokker-Planck equations, and quantum evolutions are characterized as majorized ordered chains along the time evolution, being the stationary states the infimum elements. Moreover, assuming a dynamics satisfying continuous majorization, the H-Boltzmann theorem is obtained as a special case for ϕ ( x ) = x ln x .

The use of wastes (organic and inorganic) in land restoration in relation to their characteristics and cost.

The great extent of degraded soils in southeast Spain makes it necessary to carry out restoration and rehabilitation strategies. In addition, the great amount of wastes produced need to be properly managed. Several types of wastes and amendments (organic and inorganic) can be applied for soil rehabilitation and land restoration. When large areas must be restored several aspects should be considered, such as availability of the waste, its characteristics, and transport. This research focuses on the characterization and the cost of 12 waste types and amendments (such as sewage sludge compost, brown peat, black peat, fertilized peat, earthworm humus, straw hay, palm tree leaves, pine bark, exfoliated vermiculite, expanded perlite, limestone outcrops, and volcanic crushed stones) obtained from four different sources. All of them were characterized following the UNE standards for soil amendments and the cost was obtained as a mean value of four different sources. The results indicate a great variability of properties between organic and inorganic materials, as was expected. Depending on the type of restoration, the characteristics, and the cost, the materials can be selected for an adequate purpose. Sewage sludge compost is a good alternative for application in large areas related to its characteristics (organic matter content and nutrient availability) and low cost. For inorganic amendments, natural limestone outcrops were the low-cost alternative. The use of both wastes (composted sewage sludge and limestone raw materials) for soil rehabilitation can facilitate the reduction of landfill disposal and add value for these wastes. Moreover, the results are very useful for scientists and engineers who deal with the development of rehabilitation and restoration strategies.

On a Dynamical Approach to Some Prime Number Sequences.

We show how the cross-disciplinary transfer of techniques from dynamical systems theory to number theory can be a fruitful avenue for research. We illustrate this idea by exploring from a nonlinear and symbolic dynamics viewpoint certain patterns emerging in some residue sequences generated from the prime number sequence. We show that the sequence formed by the residues of the primes modulo k are maximally chaotic and, while lacking forbidden patterns, unexpectedly display a non-trivial spectrum of Renyi entropies which suggest that every block of size m > 1 , while admissible, occurs with different probability. This non-uniform distribution of blocks for m > 1 contrasts Dirichlet's theorem that guarantees equiprobability for m = 1 . We then explore in a similar fashion the sequence of prime gap residues. We numerically find that this sequence is again chaotic (positivity of Kolmogorov-Sinai entropy), however chaos is weaker as forbidden patterns emerge for every block of size m > 1 . We relate the onset of these forbidden patterns with the divisibility properties of integers, and estimate the densities of gap block residues via Hardy-Littlewood k-tuple conjecture. We use this estimation to argue that the amount of admissible blocks is non-uniformly distributed, what supports the fact that the spectrum of Renyi entropies is again non-trivial in this case. We complete our analysis by applying the chaos game to these symbolic sequences, and comparing the Iterated Function System (IFS) attractors found for the experimental sequences with appropriate null models.

Successful treatment of multidrug-resistant Pseudomonas aeruginosa breakthrough bacteremia with ceftolozane/tazobactam.

INTRODUCTION: Ceftolozane/tazobactam is a novel antibiotic approved for the treatment of complicated intra-abdominal and complicated urinary tract infections. CASE DESCRIPTION: We describe the use of off-label ceftolozane/tazobactam in the management of a multidrug-resistant Pseudomonas aeruginosa bacteremia that was already being treated with colistin and amikacin, the only active antibiotics according to the antibiogram.

Distinguishability notion based on Wootters statistical distance: Application to discrete maps.

We study the distinguishability notion given by Wootters for states represented by probability density functions. This presents the particularity that it can also be used for defining a statistical distance in chaotic unidimensional maps. Based on that definition, we provide a metric d¯ for an arbitrary discrete map. Moreover, from d¯, we associate a metric space with each invariant density of a given map, which results to be the set of all distinguished points when the number of iterations of the map tends to infinity. Also, we give a characterization of the wandering set of a map in terms of the metric d¯, which allows us to identify the dissipative regions in the phase space. We illustrate the results in the case of the logistic and the circle maps numerically and analytically, and we obtain d¯ and the wandering set for some characteristic values of their parameters. Finally, an extension of the metric space associated for arbitrary probability distributions (not necessarily invariant densities) is given along with some consequences. The statistical properties of distributions given by histograms are characterized in terms of the cardinal of the associated metric space. For two conjugate variables, the uncertainty principle is expressed in terms of the diameters of the associated metric space with those variables.

Bitter Melon Extract Promotes Granulation Tissue Growth and Angiogenesis in the Diabetic Wound.

OBJECTIVE: Bitter melon is a plant fruit that has been shown to exert a hypoglycemic effect when used systemically in patients with diabetes. This study was designed to investigate the topical effect of bitter melon on diabetic wounds using the wound chamber model in rats. DESIGN: Two bilateral wound chambers were implanted subcutaneously in the thoracic-lumbar region of male Sprague-Dawley rats. Diabetes was induced with streptozotocin 7 days after implantation of wound chambers. After 24 hours of induction of diabetes, aqueous extract of bitter melon was injected into 1 wound chamber, and saline (0.9% sodium chloride solution) was injected into the contralateral chamber once daily for 3 days. Wound fluid was collected on day 4 for analysis, following which rats were euthanized. The granulation tissue encapsulating the wound chamber was removed and processed for histology. Controls included diabetic rats with wound chambers injected with saline (instead of bitter melon) and nondiabetic rats with wound chambers injected with bitter melon. RESULTS: In rats with diabetes, wound granulation tissue treated with bitter melon was well formed, with distinct cellular layers, whereas the saline-treated granulation tissue showed a severe loss of tissue organization and blood vessels. Moreover, the bitter melon treatment increased angiogenesis in the diabetic granulation tissue, marked by abundant microvessels and large blood vessels. In nondiabetic rats, no differences in wound granulation tissues were observed between saline- and bitter melon-treated groups. Bitter melon treatment had no effect on systemic blood glucose levels or insulin receptor substrate 1, suggesting that its stimulatory effect on diabetic granulation tissue was not due to alteration of systemic blood glucose levels. CONCLUSIONS: When applied locally to diabetic wounds, bitter melon extract prevents regression of granulation tissue and blood vessels, thus accelerating and improving wound healing.

Faecal calprotectin, an useful marker in discriminating between inflammatory bowel disease and functional gastrointestinal disorders. / Calprotectina fecal, marcador eficaz en la diferenciación de enfermedades inflamatorias intestinales y trastornos funcionales gastrointestinales.

INTRODUCTION: Diagnostic discrimination between inflammatory bowel disease (IBD) and functional gastrointestinal disorders is complex, as they cause similar signs and symptoms. Faecal calprotectin (FC) is a useful marker in this context, and can be used to select patients who will most benefit from colonoscopy. The aim of this study was to evaluate the utility of FC in discriminating between organic disease and functional disorders. MATERIAL AND METHODS: The study included 264 patients presenting with gastrointestinal complaints consistent with an organic pathology. FC levels were determined and diagnostic accuracy was assessed using the area under the curve obtained from the final diagnosis. RESULTS: Calprotectin levels in organic bowel disease patients were significantly higher (median 254µg/g; 95% confidence interval [CI], interquartile range 105-588.5) than in functional disease patients (95µg/g; 95% CI, 47.25-243.92) (P<.0001). Similarly, in patients with IBD, the values obtained were higher (270.85µg/g; 95% CI, 96.85-674.00) than in those with irritable bowel syndrome (79.70µg/g; 95% CI, 36.50-117.25) (P<.0001). For a cut-off of 150µg/g, FC had an area under the ROC curve to discriminate between organic and functional disease of 0.718, and 0.872 to discriminate between irritable bowel syndrome and IBD. CONCLUSION: Our study supports the importance of FC as a marker in the evaluation of patients with IBD. The best diagnostic accuracy is obtained at a cut-off value of 150µg/g.

Arthroscopic stabilisation of an acute acromioclavicular dislocation grade III in a patient with ectopic insertion of the pectoralis minor: technical considerations.

The different approaches used in arthroscopic stabilisation of the acromioclavicular joint are well known. However, and despite a great incidence of ectopic pectoralis minor insertion, an alternative choice for the use of arthroscopic portal has not being sufficiently described. Here, we describe a case of acute acromioclavicular dislocation grade III. The arthroscopic stabilisation was achieved using the TightRope (Arthrex, Naples, USA) implant. Through this technique, the approach to the articular portion of the coracoid process can be made intra-articularly or from the subacromial space. We accessed intra-articularly, by opening the rotator interval to reach the coracoid process from the joint cavity. After opening the rotator interval, an ectopic insertion of the pectoralis minor was observed. The choice of approach of the coracoid process from the subacromial space would have complicated the intervention, making it necessary to sever the ectopic tendon to complete the technique, lengthening the surgical time and increasing the chance of complications. For this reason, the use of a standard posterior portal providing intra-articular arthroscopic access through the rotator interval is recommended since the aforementioned anatomical variation is not infrequent. Level of evidence Therapeutic studies-investigating the results of treatment, Level V.

Wastewater Biosolid Composting Optimization Based on UV-VNIR Spectroscopy Monitoring.

Conventional wastewater treatment generates large amounts of organic matter-rich sludge that requires adequate treatment to avoid public health and environmental problems. The mixture of wastewater sludge and some bulking agents produces a biosolid to be composted at adequate composting facilities. The composting process is chemically and microbiologically complex and requires an adequate aeration of the biosolid (e.g., with a turner machine) for proper maturation of the compost. Adequate (near) real-time monitoring of the compost maturity process is highly difficult and the operation of composting facilities is not as automatized as other industrial processes. Spectroscopic analysis of compost samples has been successfully employed for compost maturity assessment but the preparation of the solid compost samples is difficult and time-consuming. This manuscript presents a methodology based on a combination of a less time-consuming compost sample preparation and ultraviolet, visible and short-wave near-infrared spectroscopy. Spectroscopic measurements were performed with liquid compost extract instead of solid compost samples. Partial least square (PLS) models were developed to quantify chemical fractions commonly employed for compost maturity assessment. Effective regression models were obtained for total organic matter (residual predictive deviation-RPD = 2.68), humification ratio (RPD = 2.23), total exchangeable carbon (RPD = 2.07) and total organic carbon (RPD = 1.66) with a modular and cost-effective visible and near infrared (VNIR) spectroradiometer. This combination of a less time-consuming compost sample preparation with a versatile sensor system provides an easy-to-implement, efficient and cost-effective protocol for compost maturity assessment and near-real-time monitoring.

In Diabetic Kidney Disease Urinary Exosomes Better Represent Kidney Specific Protein Alterations Than Whole Urine.

BACKGROUND: Predicting or diagnosing underlying kidney disease by analyzing whole urine remains the mainstay of nephrology practice. However, whole urine is a poor compartment to assess many structural changes in the kidney because whole urine contains only a few proteins derived from the kidney itself. Urinary exosomes, on the other hand, which are derived from the kidney, contain proteins secreted by the kidney. We experimentally tested the hypothesis that 'urinary exosomes more faithfully represent changes in the kidney tissue than whole urine'. A direct comparison between whole urine and urine exosomal levels of two chosen kidney disease markers, gelatinase and ceruloplasmin, was carried out on diabetic kidney disease patients. METHODS: Urinary exosomes were separated from whole urine by sequential centrifugation including ultra-centrifugation. Gelatinase activity was measured using fluorosceinated gelatin as the substrate, and ceruloplasmin was measured by sandwich ELISA. A few kidney specimens from patients biopsied for atypical features were histochemically stained for validation of the biochemical results. RESULTS: We found that changes in both, gelatinase (decreased activity) and ceruloplasmin (increased levels), in the urinary exosomes of diabetic kidney patients were in agreement with the alterations of these two proteins in the kidney tissue. In contrast, the levels of these two proteins in whole urine were highly variable and did not correlate with levels in the diabetic kidney tissue. CONCLUSION: In conclusion, these results confirmed our hypothesis that protein markers in urinary exosomes better reflected the underlying protein changes in the kidney than in whole urine samples.

Root growth dynamics linked to above-ground growth in walnut (Juglans regia).

BACKGROUND AND AIMS: Examination of plant growth below ground is relatively scant compared with that above ground, and is needed to understand whole-plant responses to the environment. This study examines whether the seasonal timing of fine root growth and the spatial distribution of this growth through the soil profile varies in response to canopy manipulation and soil temperature. METHODS: Plasticity in the seasonal timing and vertical distribution of root production in response to canopy and soil water manipulation was analysed in field-grown walnut (Juglans regia 'Chandler') using minirhizotron techniques. KEY RESULTS: Root production in walnuts followed a unimodal curve, with one marked flush of root growth starting in mid-May, with a peak in mid-June. Root production declined later in the season, corresponding to increased soil temperature, as well as to the period of major carbohydrate allocation to reproduction. Canopy and soil moisture manipulation did not influence the timing of root production, but did influence the vertical distribution of roots through the soil profile. Water deficit appeared to promote root production in deeper soil layers for mining soil water. Canopy removal appeared to promote shallow root production. CONCLUSIONS: The findings of this study add to growing evidence that root growth in many ecosystems follows a unimodal curve with one marked flush of root growth in coordination with the initial leaf flush of the season. Root vertical distribution appeared to have greater plasticity than timing of root production in this system, with temperature and/or carbohydrate competition constraining the timing of root growth. Effects on root distribution can have serious impacts on trees, with shallow rooting having negative impacts in years with limited soil water or positive impacts in years with wet springs, and deep rooting having positive impacts on soil water mining from deeper soil layers but negative impacts in years with wet springs.