Performance of machine-learning approach for prediction of pre-eclampsia in a middle-income country.

OBJECTIVE: Pre-eclampsia (PE) is a serious complication of pregnancy associated with maternal and fetal morbidity and mortality. As current prediction models have limitations and may not be applicable in resource-limited settings, we aimed to develop a machine-learning (ML) algorithm that offers a potential solution for developing accurate and efficient first-trimester prediction of PE. METHODS: We conducted a prospective cohort study in Mexico City, Mexico to develop a first-trimester prediction model for preterm PE (pPE) using ML. Maternal characteristics and locally derived multiples of the median (MoM) values for mean arterial pressure, uterine artery pulsatility index and serum placental growth factor were used for variable selection. The dataset was split into training, validation and test sets. An elastic-net method was employed for predictor selection, and model performance was evaluated using area under the receiver-operating-characteristics curve (AUC) and detection rates (DR) at 10% false-positive rates (FPR). RESULTS: The final analysis included 3050 pregnant women, of whom 124 (4.07%) developed PE. The ML model showed good performance, with AUCs of 0.897, 0.963 and 0.778 for pPE, early-onset PE (ePE) and any type of PE (all-PE), respectively. The DRs at 10% FPR were 76.5%, 88.2% and 50.1% for pPE, ePE and all-PE, respectively. CONCLUSIONS: Our ML model demonstrated high accuracy in predicting pPE and ePE using first-trimester maternal characteristics and locally derived MoM. The model may provide an efficient and accessible tool for early prediction of PE, facilitating timely intervention and improved maternal and fetal outcome. © 2023 The Authors. Ultrasound in Obstetrics & Gynecology published by John Wiley & Sons Ltd on behalf of International Society of Ultrasound in Obstetrics and Gynecology.

Eficiencia de un enfoque de aprendizaje automático para la predicción de la preeclampsia en un país de ingresos medios OBJETIVO: La preeclampsia (PE) es una complicación grave del embarazo asociada a morbilidad y mortalidad materna y del feto. Dado que los modelos de predicción actuales tienen limitaciones y pueden no ser aplicables en situaciones con recursos limitados, se propuso desarrollar un algoritmo de aprendizaje automático (AA) que ofrezca una solución con potencial para desarrollar una predicción precisa y eficiente de la PE en el primer trimestre. MÉTODOS: Se realizó un estudio de cohorte prospectivo en Ciudad de México para desarrollar un modelo de predicción de la PE pretérmino (PEp) en el primer trimestre utilizando AA. Para la selección de variables se utilizaron las características maternas y los múltiplos de la mediana (MdM) obtenidos localmente para la presión arterial media, el índice de pulsatilidad de la arteria uterina y el factor de crecimiento placentario sérico. El conjunto de datos se dividió en subconjuntos de datos de entrenamiento, de validación y de test estadístico. Se empleó un método de red elástica para la selección de predictores, y el rendimiento del modelo se evaluó mediante el área bajo la curva de características operativas del receptor (ABC) y las tasas de detección (TD) con tasas de falsos positivos (TFP) del 10%. RESULTADOS: El análisis final incluyó a 3050 mujeres embarazadas, de las cuales 124 (4,07%) desarrollaron PE. El modelo de AA mostró una buena eficiencia, con un ABC de 0,897, 0,963 y 0,778 para la PEp, la PE de aparición temprana (PEat) y cualquier tipo de PE (todas las PE), respectivamente. Las TD con TFP del 10% fueron del 76,5%, 88,2% y 50,1% para la PEp, PEat y todas las PE, respectivamente. CONCLUSIONES: Nuestro modelo de AA demostró una alta precisión en la predicción de la PEp y la PEat utilizando características maternas del primer trimestre y MdM calculados localmente. El modelo puede proporcionar una herramienta eficiente y accesible para la predicción temprana de la PE, facilitando la intervención oportuna y la mejora de los resultados maternos y del feto.

Regulatory Mechanisms of Muscle Mass: The Critical Role of Resistance Training in Children and Adolescent.

Muscle mass and strength are subjected to several regulations. We found endocrine signals such as growth hormone, insulin-like growth factor 1, testosterone, thyroid hormones, and glucocorticoids among them. Neural inputs also influence muscle development, modulating mass and strength. Among the external stimuli that modulate these muscular features is physical training such as resistance and endurance training. Specifically, resistance training can mediate an increase in muscle mass by hypertrophy in adults, but the effects in children and adolescents are full of myths for most of the population. However, the evidence shows that the impact of resistance training on children and adolescents is clear and provides a wide range of benefits. However, qualified professionals must be available since exercise prescription and subsequent supervision must follow this population's abilities, needs, and interests.

Drought impact on forest carbon dynamics and fluxes in Amazonia.

In 2005 and 2010 the Amazon basin experienced two strong droughts, driven by shifts in the tropical hydrological regime possibly associated with global climate change, as predicted by some global models. Tree mortality increased after the 2005 drought, and regional atmospheric inversion modelling showed basin-wide decreases in CO2 uptake in 2010 compared with 2011 (ref. 5). But the response of tropical forest carbon cycling to these droughts is not fully understood and there has been no detailed multi-site investigation in situ. Here we use several years of data from a network of thirteen 1-ha forest plots spread throughout South America, where each component of net primary production (NPP), autotrophic respiration and heterotrophic respiration is measured separately, to develop a better mechanistic understanding of the impact of the 2010 drought on the Amazon forest. We find that total NPP remained constant throughout the drought. However, towards the end of the drought, autotrophic respiration, especially in roots and stems, declined significantly compared with measurements in 2009 made in the absence of drought, with extended decreases in autotrophic respiration in the three driest plots. In the year after the drought, total NPP remained constant but the allocation of carbon shifted towards canopy NPP and away from fine-root NPP. Both leaf-level and plot-level measurements indicate that severe drought suppresses photosynthesis. Scaling these measurements to the entire Amazon basin with rainfall data, we estimate that drought suppressed Amazon-wide photosynthesis in 2010 by 0.38 petagrams of carbon (0.23-0.53 petagrams of carbon). Overall, we find that during this drought, instead of reducing total NPP, trees prioritized growth by reducing autotrophic respiration that was unrelated to growth. This suggests that trees decrease investment in tissue maintenance and defence, in line with eco-evolutionary theories that trees are competitively disadvantaged in the absence of growth. We propose that weakened maintenance and defence investment may, in turn, cause the increase in post-drought tree mortality observed at our plots.

Dexmedetomidine metabolic clearance is not affected by fat mass in obese patients.

BACKGROUND: Obesity has been associated with reduced dexmedetomidine clearance, suggesting impaired hepatic function or reduced hepatic blood flow. The aim of this study was to clarify the effect of obesity in dexmedetomidine metabolic clearance. METHODS: Forty patients, ASA I-III, 18-60 yr old, weighing 47-126 kg, scheduled for abdominal laparoscopic surgery, were enrolled. Anaesthetic agents (propofol, remifentanil, and dexmedetomidine) were dosed based on lean body weight measured by dual X-ray absorptiometry. Serial venous samples were drawn during and after dexmedetomidine infusion. A pharmacokinetic analysis was undertaken using non-linear mixed-effect models. In the modelling approach, the total body weight, lean body weight, and adjusted body weight were first tested as size descriptors for volumes and clearances. Hepatic blood flow, liver histopathology, liver enzymes, and gene expression of metabolic enzymes (UGT2B10 and UGT1A4) were tested as covariates of dexmedetomidine metabolic clearance. A decrease in NONMEM objective function value (ΔOFV) of 3.84 points, for an added parameter, was considered significant at the 0.05 level. RESULTS: A total of 637 dexmedetomidine serum samples were obtained. A two-compartmental model scaled to measured lean weight adequately described the dexmedetomidine pharmacokinetics. Liver blood flow was a covariate for dexmedetomidine clearance (ΔOFV=-5.878). Other factors, including fat mass, histopathological damage, and differential expression of enzymes, did not affect the dexmedetomidine clearance in the population studied (ΔOFV<3.84). CONCLUSIONS: We did not find a negative influence of obesity in dexmedetomidine clearance when doses were adjusted to lean body weight. Liver blood flow showed a significant effect on dexmedetomidine clearance. CLINICAL TRIAL REGISTRATION: NCT02557867.

Effects of inter- and intra-aggregate magnetic dipolar interactions on the magnetic heating efficiency of iron oxide nanoparticles.

Iron oxide nanoparticles have found an increasing number of biomedical applications as sensing or trapping platforms and therapeutic and/or diagnostic agents. Most of these applications are based on their magnetic properties, which may vary depending on the nanoparticle aggregation state and/or concentration. In this work, we assess the effect of the inter- and intra-aggregate magnetic dipolar interactions on the heat dissipation power and AC hysteresis loops upon increasing the nanoparticle concentration and the hydrodynamic aggregate size. We observe different effects produced by inter- (long distance) and intra-aggregate (short distance) interactions, resulting in magnetizing and demagnetizing effects, respectively. Consequently, the heat dissipation power under alternating magnetic fields strongly reflects such different interacting phenomena. The intra-aggregate interaction results were successfully modeled by numerical simulations. A better understanding of magnetic dipolar interactions is mandatory for achieving a reliable magnetic hyperthermia response when nanoparticles are located into biological matrices.

Exogenous lipid pneumonia related to long-term use of Vicks VapoRub® by an adult patient: a case report.

BACKGROUND: Use of petroleum-based over the counter remedies such as Vicks VapoRub to alleviate symptoms of rhinitis is common and can be effective, but carries under-appreciated risks of adverse side effects. In this case report we highlight Exogenous Lipoid Pneumonia (ELP), an uncommon condition that results from accumulation of exogenous lipids in the alveoli, as an adverse side effect of long-term Vicks VapoRub use. CASE PRESENTATION: We present the case of an 85-year-old female patient with ELP apparently due to continuous application of Vicks VapoRub® to her nostrils to alleviate chronic rhinitis. She was diagnosed incidentally via chest radiograph and computed tomography (CT) scan done as follow up to finding elevated C-reactive Protein during a routine exam. The CT scan revealed a pulmonary consolidation in the lower lobe of the right lung with fat density combined with low density areas associated with focal ground-glass opacities. The patient was advised to discontinue use of petroleum-based products, and was prescribed intranasal corticosteroids for her rhinitis. Follow up 2 years later showed that the lipid consolidation had diminished in size by approximately 10 %. CONCLUSION: Physicians must be aware that ELP can develop as a result of long-term application of petroleum-based oils and ointments to the nose and discourage such use of these products. Patients who have used petroleum-based products in this way should be screened for ELP. CT scan is the best imaging modality for establishing the diagnosis. The treatment of this condition is not well defined, but, as shown in this case, the size of the lipid mass can decrease after use of petroleum based substances is discontinued.

Trends in the incidence of hip fracture in Gran Canaria, Canary Islands, Spain: 2007-2011 versus 1989-1993.

UNLABELLED: Hip fracture incidence in the Canaries was studied in two 5-year periods (1989-1993 and 2008-2011). The incidence in 2007-2011 was 24 % higher than in 1989, but did not differ between 2007-2011 and 1993. These findings suggest a trend to stabilize the incidence of hip fracture. INTRODUCTION: A dramatic increase in hip fractures between 1988 and 2002 was reported in Northern Spain. We performed the present study in Gran Canaria, the Canary Islands, to compare changes in the incidence of hip fracture between 1989-1993 and 2007-2011. METHODS: We recorded every osteoporotic hip fracture admitted to any hospital in Gran Canaria in the population 50 years of age or older. RESULTS: In 1989-1993, we collected 1175 hip fractures (72 % women; mean age 78.2 ± 9.9 years), and the total incidence rate was 152.1 cases/100,000 population/year. In 2007-2011, we collected 2222 hip fracture cases (71 % women; mean age 79 ± 9.8 years). The total incidence was 180.9/100,000/year. A Poisson model showed that the incidence of fractures increased by 7.1 % (95 % CI = 3.1 %; 11.8 %) each year in 1989-1993, while there was no statistically significant variation (p = 0.515) during the period 2007-2011. The incidence in 2007-2011 was 24 % higher than in 1989 (first year in the first period) but did not differ between 2007-2011 and 1993 (the last year of the first period). Incidence rates were 76.7 % (95 % CI = 63.9 %; 90.5 %) higher in women than in men, but the female/male ratio remained unchanged. The age-adjusted incidence of hip fractures increased by 7.3 % each year from 1989 to 1993. The proportions of trochanter and cervical fractures were similar in the two time periods, but the mean hospital stay was reduced from 11 days in 1989-1993 to 7 days in 2007-2011. CONCLUSIONS: These findings suggest a trend to stabilize the incidence of hip fracture in the Canary Islands due to a decrease in men, while in women, the incidence increased.

Ammonium depletion associated with the COVID-19 pandemic in the Mexican Caribbean.

The Mexican Caribbean contributes significantly to Mexico's gross national product. The number of tourists declined from 16.7 million in 2019 to 8.8 million in 2020 due to the COVID-19 pandemic, with a rapid recovery of 13.5 million in 2021. Wastewater discharge is the primary contamination source associated with the tourism sector's demand for goods and services. Water quality could improve due to fewer tourists arriving during the COVID-19 sanitary emergency. This study aimed to quantify ammonium concentrations at eleven locations to evaluate water quality during the sanitary restriction due to the pandemic in the Mexican Caribbean. The ammonium concentrations were 85 % (Nov-2019), 89 % (Feb-2020), and 86 % (Feb-2021) higher than in Nov-2020, where six of the eleven sampled stations were below the detection limit (0.15 µM). Lower ammonium concentrations coincide with the sanitary restriction period and a decrease in affluent tourists.

A fast method for the quantitation of key metabolites of the methionine pathway in liver tissue by high-resolution mass spectrometry and hydrophilic interaction ultra-performance liquid chromatography.

We developed an assay for the extraction and simultaneous quantitation of five key metabolites of the methionine metabolic pathway in liver tissue. The metabolites included were 5'-methylthioadenosine, methionine, homocysteine, S-adenosyl-L-homocysteine, and S-adenosyl-L-methionine. The metabolites were extracted using a bead-based homogenization method, and quantitation was carried out using hydrophilic interaction chromatography and time-of-flight mass spectrometry. The extraction procedure was optimized by testing the effect of various solvent combinations. The chromatographic method was optimized for peak shape, signal intensity, and carry-over. With a total chromatographic run time of 5 min, this assay is suitable for the analysis of large sample sets. Time-of-flight mass spectrometry provided high mass accuracy which, combined with isotope pattern matching and use of chemical standards, guarantees high specificity. Moreover, by operating the mass spectrometer in enhanced duty cycle mode the signal strength for the analytes increased three- to tenfold in comparison with the generic full-scan mode. For quantitation, a matrix-spiked calibration method was used. The lowest analyte levels detected and quantified using our method were within the range of concentrations found in the liver. The inter-day coefficients of variance for the analytes were between 5 and 15% in pooled tissue samples. Interestingly, the CVs between individual liver tissue aliquots were about twice as high. Additional experiments suggested that this higher variability was caused by uneven distribution of the analytes within the liver. In conclusion, an optimized and robust assay is now available for the extraction and quantification of key metabolites in the methionine metabolic pathway.

Extracellular vesicles released by steatotic hepatocytes alter adipocyte metabolism.

The composition of extracellular vesicles (EVs) is altered in many pathological conditions, and their molecular content provides essential information on features of parent cells and mechanisms of crosstalk between cells and organs. Metabolic Syndrome (MetS) is a cluster of clinical manifestations including obesity, insulin resistance, dyslipidemia and hypertension that increases the risk of cardiovascular disease and type 2 diabetes mellitus. Here, we investigated the crosstalk between liver and adipocytes by characterizing EVs secreted by primary hepatocytes isolated from Zucker rat model, and studied the effect they have on 3T3-L1 adipocytes. We found that steatotic hepatocytes secrete EVs with significantly reduced exosomal markers in comparison with their lean counterpart. Moreover, proteomic analysis revealed that those EVs reflect the metabolic state of the parent cell in that the majority of proteins upregulated relate to fat metabolism, fatty acid synthesis, glycolysis, and pentose phosphate pathway. In addition, hepatocytes-secreted EVs influenced lipolysis and insulin sensitivity in recipient 3T3-L1 adipocytes. Untargeted metabolomic analysis detected alterations in different adipocyte metabolic pathways in cells treated with hepatic EVs. In summary, our work showed that steatosis has a significant impact in the amount and composition of EVs secreted by hepatocytes. Moreover, our data point to the involvement of hepatic-EVs in the development of pathologies associated with MetS.

Implementation of a rapid recovery protocol in total knee arthroplasty. A randomized controlled trial. / Implantación de un protocolo de recuperación precoz en artroplastia total de rodilla. Ensayo clínico aleatorizado.

BACKGROUND: Rapid recovery (RP) in total knee arthroplasty may increase the functionality while reducing costs. The aim of this study is to prove the benefits of a rapid recovery program compared to our classic protocol. PATIENTS AND METHODS: We performed a RCT (NCT03823573) in patients undergoing otal knee arthroplasty. Intervention group (RP protocol) received local infiltration of levo-bupivacaine in the periarticular tissue and supervized ambulation 4-6h after surgery. Control (C) group received a femoral nerve block with levo-bupivacaine, while a drain was used. Ambulation after its removal. All the patients completed an Oxford Knee Score prior to surgery and 6 months after discharge. An ecodoppler to assess the presence of deep vein thrombosis was made one month after discharge. Minimum follow-up was of 6 months. RESULTS: A total of 175 patients were included in the trial (92 patients in the control group, 83 patients in the RP group). There were no differences in sex, age, implanted prosthesis, hemoglobin drop, need for transfusion, range of motion on discharge (C: 82.6°, RP: 85°) and at the end of the follow-up (C: 105.1, RP: 106.6), Oxford Knee Score improvement (C: 17.5 points; RP: 19.3 points), patient satisfaction or re-admissions at the emergency department (C: 7.6%; RP: 10.8%). Significancy was found on time of ischemia (C: 81.29min; RP: 85.35min; P=0.03), need for morphine shots (C: 19.7%; RP: 38.6%; P=0.007), hospital stay (C: 3.84 days; RP: 2.54 days, P<0.0001) and time until ambulation (C: 2.46 days; RP: 0.23 days; P<0.0001). CONCLUSION: Rapid recovery protocols can reduce hospital stay without increasing complications or need for re-admission.

[Translated article] Implementation of a rapid recovery protocol in total knee arthroplasty. A randomised controlled trial.

BACKGROUND: Rapid recovery (RP) in total knee arthroplasty may increase the functionality while reducing costs. The aim of this study is to prove the benefits of a rapid recovery programme compared to our classic protocol. PATIENTS AND METHODS: We performed a RCT (NCT03823573) in patients undergoing otal knee arthroplasty. Intervention group (RP protocol) received local infiltration of levo-bupivacaine in the periarticular tissue and supervized ambulation 4-6h after surgery. Control (C) group received a femoral nerve block with levo-bupivacaine, while a drain was used. Ambulation after its removal. All the patients completed an Oxford Knee Score prior to surgery and 6 months after discharge. An ecodoppler to assess the presence of deep vein thrombosis was made 1 month after discharge. Minimum follow-up was of 6 months. RESULTS: A total of 175 patients were included in the trial (92 patients in the control group, 83 patients in the RP group). There were no differences in sex, age, implanted prosthesis, haemoglobin drop, need for transfusion, range of motion on discharge (C: 82.6°, RP: 85°) and at the end of the follow-up (C: 105.1, RP: 106.6), Oxford knee score improvement (C: 17.5 points; RP: 19.3 points), patient satisfaction or re-admissions at the emergency department (C: 7.6%; RP: 10.8%). Significancy was found on time of ischaemia (C: 81.29min; RP: 85.35min; p=.03), need for morphine shots (C: 19.7%; RP: 38.6%; p=.007), hospital stay (C: 3.84 days; RP: 2.54 days, p<.0001) and time until ambulation (C: 2.46 days; RP: 0.23 days; p<.0001). CONCLUSION: Rapid recovery protocols can reduce hospital stay without increasing complications or need for re-admission.

Consensus and recommendations on vaginal-cuff Brachytherapy of the Spanish Brachytherapy Groups of SEOR and SEFM.

PURPOSE/OBJECTIVE(S): On October 5, 2018, a meeting of the Spanish Society of Radiation Oncology (SEOR) Brachytherapy Group was held, in collaboration with the Spanish Society of Medical Physics (SEFM), with the aim of preparing a consensus document on postoperative vaginal-cuff brachytherapy (VCBT). MATERIALS/METHODS: A survey including 42 questions was sent to Spanish Radiation Oncology Centres before the meeting. The survey items included: experience in VCBT, technique indications, previous patient preparation, applicator type, implant procedure, computerized tomography (CT) simulation, definition of target volumes and organs at risk (OAR), dose prescription, fractionation, treatment planning, dosimetric parameters and constraints to OAR. Thirty-three centres answered the survey. Statistical analysis of the survey considered that there was consensus when there was ≥ 85% of agreement related to a survey item, otherwise an item with < 85% of agreement would be discussed during the meeting to reach consensus. RESULTS: The results of the survey are reported here. The mean number of patients treated per centre in 2017 was 52 ± 41 (range 7-175), and the mean number of procedures per centre was 175 ± 150 (range 24-701).There was consensus on: the indications, applicator type, the OAR to be considered, the prescription point, standardisation and dosimetric quality parameters. There was no consensus on: patient preparation for the implant, the need for performing CT simulation and the frequency, the length of the vagina to be treated, if CTV should be delimited, the definition of the clinical target volume, fractionation, overall EQD2, active source length, separation between dwelling stepping source positions, if considering the uniformity/maximum values for dwelling stepping sources, the optimization mode, and the limiting doses to the OAR. After presenting the results of the survey, the consensus meeting discussion focused on the issues for which there was no consensus. CONCLUSION: A consensus document on postoperative VCBT of the Spanish Brachytherapy Groups of SEOR-SEFM was elaborated.

An evaluation of a new instrument to measure organisational safety culture values and practices.

The main aim of this research is to evaluate a safety culture measuring instrument centred upon relevant organisational values and practices related to the safety management system. Seven dimensions that reflect underlying safety meanings are proposed. A second objective is to explore the four cultural orientations in the field of safety arising from the competing values framework. The study sample consisted of 299 participants from five companies in different sectors. The results show six dimensions of organisational values and practices and different company profiles in the organisations studied. The four cultural orientations proposed by the competing values framework are not confirmed. Nevertheless, a coexistence of diverse cultural orientations or paradoxes in the companies is observed.

Unraveling viscosity effects on the hysteresis losses of magnetic nanocubes.

Hysteresis losses in magnetic nanoparticles constitute the basis of magnetic hyperthermia for delivering a local thermal stress. Nevertheless, this therapeutic modality is only to be realised through a careful appraisal of the best possible intrinsic and extrinsic conditions to the nanoparticles for which they maximise and preserve their heating capabilities. Low frequency (100 kHz) hysteresis loops accurately probe the dynamical magnetic response of magnetic nanoparticles in a more reliable manner than calorimetry measurements, providing conclusive quantitative data under different experimental conditions. We consider here a set of iron oxide or cobalt ferrite nanocubes of different sizes, through which we experimentally and theoretically study the influence of the viscosity of the medium on the low frequency hysteresis loops of magnetic colloids, and hence their ability to produce and dissipate heat to the surroundings. We analyse the role of nanoparticle size, size distribution, chemical composition, and field intensity in making the magnetisation dynamics sensitive to viscosity. Numerical simulations using the stochastic Landau-Lifshitz-Gilbert equation model the experimental observations in excellent agreement. These results represent an important contribution towards predicting viscosity effects and hence to maximise heat dissipation from magnetic nanoparticles regardless of the environment.

BLOC-1 deficiency causes alterations in amino acid profile and in phospholipid and adenosine metabolism in the postnatal mouse hippocampus.

Biogenesis of lysosome-related organelles complex-1 (BLOC-1) is a protein complex involved in the formation of endosomal tubular structures that mediates the sorting of protein cargoes to specialised compartments. In this study, we present insights into the metabolic consequences caused by BLOC-1 deficiency in pallid mice, which carry a null mutation in the Bloc1s6 gene encoding an essential component of this complex. The metabolome of the hippocampus of pallid mice was analysed using an untargeted, liquid chromatography-coupled mass spectrometric approach. After data pre-treatment, statistical analysis and pathway enrichment, we have identified 28 metabolites that showed statistically significant changes between pallid and wild-type control. These metabolites included amino acids, nucleobase-containing compounds and lysophospholipids. Interestingly, pallid mice displayed increased hippocampal levels of the neurotransmitters glutamate and N-acetyl-aspartyl-glutamic acid (NAAG) and their precursor glutamine. Expression of the sodium-coupled neutral amino acid transporter 1 (SNAT1), which transports glutamine into neurons, was also upregulated. Conversely, levels of the neurotransmitter precursors phenylalanine and tryptophan were decreased. Interestingly, many of these changes could be mapped to overlapping metabolic pathways. The observed metabolic alterations are likely to affect neurotransmission and neuronal homeostasis and in turn could mediate the memory and behavioural impairments observed in BLOC-1-deficient mice.

A simple 1+ dimensional model of rowing mimics observed forces and motions.

We have devised a simple, yet predictive model of the mechanics of both sculling and sweep rowing that reasonably mimics observed kinematic and force data. Our physical model is largely based upon the model proposed by Alexander [Alexander, F. H. (1925). The theory of rowing. In Proceedings of the University of Durham Philosophical Society (pp. 160-179).]. The model's primary features include: one dimensional momentum balance, a point mass rower, infinitely stiff oars with inertia and non-infinitesimal stroke angles, and quadratic relationships between force and velocity for the boat and oar blade. Using an inverse dynamics approach, we are able to construct reasonable fits to force and kinematic data of real rowing. We show that the model is able to reasonably well predict boat velocity even when we do not fit for it. A sensitivity analysis shows that the quality of fit is more sensitive to the boat and oar drag coefficients than to other physical parameters. Allowing oar slip (C(D) < infinity) proves to be a necessary model ingredient but, for example, allowing for oar flexibility does not improve the quality of fit. The model seems to have the key terms and a minimum of superfluous terms for investigations of rowing.