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The global proliferation of harmful algal blooms poses an increasing threat to water resources, recreation and ecosystems. Predicting the occurrence of these blooms is therefore needed to assist water managers in making management decisions to mitigate their impact. Evaluation of the potential for forecasting of algal blooms using the phytoplankton community model PROTECH was undertaken in pseudo-real-time. This was achieved within a data assimilation scheme using the Ensemble Kalman Filter to allow uncertainties and model nonlinearities to be propagated to forecast outputs. Tests were made on two mesotrophic lakes in the English Lake District, which differ in depth and nutrient regime. Some forecasting success was shown for chlorophyll a , but not all forecasts were able to perform better than a persistence forecast. There was a general reduction in forecast skill with increasing forecasting period but forecasts for up to four or five days showed noticeably greater promise than those for longer periods. Associated forecasts of phytoplankton community structure were broadly consistent with observations but their translation to cyanobacteria forecasts was challenging owing to the interchangeability of simulated functional species. [ABSTRACT FROM AUTHOR]

Excessive algal blooms, some of which can be toxic, are the most obvious symptoms of nutrient enrichment and can be exacerbated by climate change. They cause numerous ecological problems and also economic costs to water companies. The process-representation of the algal community model PROTECH was tested within the extended Generalised Likelihood Uncertainty Estimation framework which includes pre-defined Limits of Acceptability for simulations. Testing was a precursor to modification of the model for real-time forecasting of algal communities that will place different demands on the model in terms of a) the simulation accuracy required, b) the computational burden associated with the inclusion of forecast uncertainties and c) data assimilation. We found that the systematic differences between the model’s representation of underwater light compared to the real lake systems studied and the uncertainties associated with nutrient fluxes will be the greatest challenges when forecasting algal blooms. [ABSTRACT FROM AUTHOR]

Purpose: Free nonvascularized toe phalangeal transfer is an established surgical option for the reconstruction of hypoplastic digits. This study assessed long-term morbidity in the feet using this technique. Methods: We reviewed 40 children treated between 1991 and 2007 by free nonvascularized toe phalangeal transfer. The diagnosis was digital hypoplasia resulting from symbrachydactyly in 33 cases, constriction ring syndrome in 3 cases, thumb hypoplasia in 3 cases, and perinatal subclavian venous thrombosis in 1 case. The patients were followed up after surgery for a mean of 10 years (range, 3–19 y). The Oxford Ankle Foot Questionnaire was administered to patients and families to assess patient symptoms and patient and parental satisfaction. We assessed toe length ratio, the presence of visible deformity, and distal hypoplasia of the donor toes clinically and radiographically. Results: Emotional problems related to foot appearance were common. We also found functional problems with footwear in some patients. All patients had floppy unstable toes with visible deformity. Increasing foot deformity was seen with growth, which led to deterioration in foot aesthetics, particularly where multiple donor toes had been harvested. We identified distal and middle phalangeal and metatarsal hypoplasia in the donor toes. Conclusions: Donor site morbidity for free toe phalangeal transfer is greater than previously documented. This should be considered during surgical decision making for reconstruction of hypoplastic digits. Preoperative counseling should include discussion regarding possible consequences of phalangeal harvest on donor toes and options for donor site reconstruction. Long-term follow-up of the donor site is essential to accurately assess results. Type of study/level of evidence: Therapeutic III. [Copyright &y& Elsevier]

Abstract: Purpose: A unilateral poorly or non-functioning kidney is a cause of hypertension in children. We report the outcomes of pediatric patients with unilateral renal parenchymal disease who underwent nephrectomy for hypertension. Materials and methods: Consecutive hypertensive children undergoing nephrectomy with a unilateral poorly or non-functioning kidney were retrospectively reviewed; preoperative and postoperative clinical variables were analyzed. Results: From July 2002 to August 2009, 21 patients (8M:13F) with average age 3.5 years and average follow-up 17.8 months were studied. Eleven patients had multicystic dysplastic kidney, 8 had reflux nephropathy, and 2 had ureteropelvic junction obstruction. Fourteen of 21 (67%) had blood pressure normalization after nephrectomy. Seven of 11 with MCDK were normotensive postoperatively compared to 6/8 patients with reflux nephropathy, and 1/2 patients with UPJ obstruction. Of the 14 patients normotensive postoperatively, 7 were on antihypertensives prior to surgery. Four of 7 patients stopped their anti-hypertensive medications postoperatively, 2 decreased from 3 and 4 medications to 1, and 1 remained on an ACE inhibitor. There were 2 patients with contralateral renal scarring, both of which remained hypertensive postoperatively. Conclusions: Nephrectomy in hypertensive pediatric patients with a unilateral poorly functioning or non-functioning kidney yielded hypertension resolution in 67% (14/21), permitting cessation or diminution of antihypertensives in many patients. Given the alternative of lifelong antihypertensives with the risk of medication non-compliance and side-effects, nephrectomy is a logical option of care which can be offered to patients and families with informed knowledge of the potential for cure. [Copyright &y& Elsevier]

Abstract: Purpose: The purpose was to compare nephrolithiasis in healthy versus medically complex gastrostomy fed children. Materials and methods: Children with nephrolithiasis with and without gastrostomy were identified by database searches from 1999 to 2009. Gastrostomy fed stone formers (GSF) were compared to an age-matched cohort of non-gastrostomy-fed stone formers (NGSF) for demographic and clinical data. Results: 16 neurologically impaired GSF (10M:6F), mean age 10.4 years (range 1.7–17.5 years), were compared to 32 matched neurologically intact NGSF. Compared to NGSF, GSF had significantly higher urine pH (6.93 vs 6.23, p = 0.001) and larger stones (14.5 vs 6.9 mm, p = 0.02) more commonly composed of calcium phosphate (7/11, 64% vs 3/28, 11%, p = 0.002). 15/16 (94%) of GSF were immobile while 0% of NGSF were immobile. GSF had lower l-spine bone density Z-scores (−3.02 vs −1, p = 0.002) but an equal rate of hypercalciuria (2/7, 29% vs 7/24, 29%, p = NS). Contributing lithogenic factors in 8/16 (50%) GSF included urinary tract infection (UTI) (5), lithogenic medications (2), and xanthinuria (1). Conclusions: Stone disease in GSF is multifactorial, and half of our study group had an identifiable risk factor for nephrolithiasis. A recurring pattern of alkaline urine and calcium phosphate stone formation was evident. GSF did not have higher rates of hypercalciuria despite chronic immobilization and markedly lower bone density. An awareness of the potential risk factors identified is mandatory for this vulnerable population. [Copyright &y& Elsevier]

Cytomics has a practical role to play in drug discovery within the immediate limitations of cell-based analyses. A more elusive goal is the clarification of the complexity of a dynamic cellular response to a drug through mathematical modelling. The common aim for drug discovery and cytomics is to bridge the molecular–cellular systems gap. The strategic challenges faced include: suitable preclinical biological models, cytometric platforms that resolve cellular or behavioural identity, analysis and visualization tools that act as integrating principles, consensus on standards and, finally, the implementation of informatics to serve the demands of decision making. Advances in all these key areas will help to address the need to identify and evaluate the origins of asymmetry and heterogeneity in cellular systems and thus reveal new opportunities for therapeutic targeting. [Copyright &y& Elsevier]

Abstract: The displacement of thousands of U.S. Gulf Coast residents in the aftermath of Hurricane Katrina is emblematic of a human migration challenge that will likely become more severe in the years and decades ahead. The Intergovernmental Panel on Climate Change (IPCC) predicts that climate change will manifest in dramatic ways-extreme weather events, droughts, heat waves, increased cyclone (hurricane, typhoon) activity, sea level rise, etc.-and some of these effects may induce large scale human migration, both within and among countries. The increasing trend of environmental migrants is clashing with widespread anti-immigrant sentiment in both developed and developing countries around the world. Some countries are describing migration-and particularly unauthorized international migration-as a “security threat” and are turning to military forces to deter or manage the human flows, a trend that is likely to grow. [Copyright &y& Elsevier]

Purpose: To determine the complication rate of a modified Skoog’s technique in the surgical treatment of Dupuytren’s contracture. Methods: A retrospective analysis was performed on 253 patients who had surgery by 1 surgeon using 1 technique with a mean follow-up period of 3.6 years. We studied the complication rate of the modified Skoog’s procedure, relating it to a grading system for disease severity. A separate prospective long-term study was performed with an unselected cohort in which disease recurrence producing contracture was investigated prospectively in a group of 75 patients. Results: Complications occurred in 46 patients. Thirty-five patients had 1 complication and 11 patients had more than 1 complication. Intraoperative complications included 6 patients with nerve injury and 1 patient with an arterial injury. Early postoperative complications before wound healing included 5 patients with digital hematoma, 24 patients with wound infection, 6 patients with sympathetic dystrophy, and 6 patients with skin slough. Late postoperative complications included 3 patients with scar contraction and 2 patients with carpal tunnel syndrome. There were 3 non–hand-related complications: 1 urinary retention, 1 left ventricular failure, and 1 myocardial infarction. Recurrence of Dupuytren’s disease occurred in 23 of 75 patients after a mean follow-up period of 9.4 years. Conclusions: The complication rate increased with the severity of disease particularly if the proximal interphalangeal joint contracture was 60° or more. There was no difference in the complication rate for patients who had surgery for primary or recurrent disease. [Copyright &y& Elsevier]

A concise, efficient synthesis is described for a terbenzimidazole that acts as a potent topoisomerase I poison. The strategy involves iterative palladium-catalyzed borinate ester cross-couplings and should be applicable to the synthesis of analogs containing heterocycles other than benzimidazole. [Copyright &y& Elsevier]

Cystic dysplasia of the rete testis (CDT) represents a diagnostically challenging condition in the pediatric population. We report a new case of CDT that differs in presentation from the majority of other cases in the literature in that the child complained of scrotal pain and had a solid mass on ultrasound. Based on this experience and a review of the literature, we recommend including CDT in the differential for all pediatric scrotal masses regardless of whether the mass is painless or painful, cystic or solid. As CDT is a benign lesion, we propose an individualized treatment of CDT. [Copyright &y& Elsevier]

Abstract: The stoichiometry of Photosystem II (PSII) to Photosystem I (PSI) reaction centres in spinach leaf segments was determined by two methods, each capable of being applied to monitor the presence of both photosystems in a given sample. One method was based on a fast electrochromic (EC) signal, which in the millisecond time scale represents a change in the delocalized electric potential difference across the thylakoid membrane resulting from charge separation in both photosystems. This method was applied to leaf segments, thus avoiding any potential artefacts associated with the isolation of thylakoid membranes. Two variations of this method, suppressing PSII activity by prior photoinactivation (in spinach and poplar leaf segments) or suppressing PSI by photo-oxidation of P700 (the chlorophyll dimer in PSI) with background far-red light (in spinach, poplar and cucumber leaf segments), each gave the separate contribution of each photosystem to the fast EC signal; the PSII/PSI stoichiometry obtained by this method was in the range 1.5–1.9 for the three plant species, and 1.5–1.8 for spinach in particular. A second method, based on electron paramagnetic resonance (EPR), gave values in a comparable range of 1.7–2.1 for spinach. A third method, which consisted of separately determining the content of functional PSII in leaf segments by the oxygen yield per single turnover-flash and that of PSI by photo-oxidation of P700 in thylakoids isolated from the corresponding leaves, gave a PSII/PSI stoichiometry (1.5–1.7) that was consistent with the above values. It is concluded that the ratio of PSII to PSI reaction centres is considerably higher than unity in typical higher plants, in contrast to a surprisingly low PSII/PSI ratio of 0.88, determined by EPR, that was reported for spinach grown in a cabinet under far-red-deficient light in Sweden [Danielsson et al. (2004) Biochim. Biophys. Acta 1608: 53–61]. We suggest that the low PSII/PSI ratio in the Swedish spinach, grown in far-red-deficient light with a lower PSII content, is not due to greater accuracy of the EPR method of measurement, as suggested by the authors, but is rather due to the growth conditions. [Copyright &y& Elsevier]

Several novel compounds have been identified that inhibit the replication of hepatitis C virus in a replicon assay with EC 50 values as low as 0.6 μM. Lead compounds were modified to investigate the possible role that zinc binding may play in inhibitor efficacy. In addition, the structure–activity relationship was explored to increase inhibitor efficacy and possibly identify favorable interactions within the currently unknown inhibitor binding pocket. The rationale for inhibitor design and biological results are presented herein. [ABSTRACT FROM AUTHOR]

Abstract: The bacterial natural product UK-1 and several structural analogs inhibit replication of the hepatitis C virus in the replicon assay, with IC50 values as low as 0.50μM. The NS3 helicase has been identified as a possible target of inhibition for several of these compounds, while the remaining inhibitors act via an undetermined mechanism. Gel shift assays suggest that helicase inhibition is a direct result of inhibitor–enzyme binding as opposed to direct RNA binding, and the ATPase activity of NS3 is not affected. The syntheses and biological results are presented herein. [Copyright &y& Elsevier]

Abstract: Background: Targeted molecular therapies (TMTs) previously have demonstrated oncologic activity in renal cell carcinoma (RCC) by reducing the size of primary tumors and metastases. Objective: To assess the cytoreductive effect of TMTs on inferior vena cava tumor thrombi. Design, setting, and participants: A multi-institutional database of patients treated with TMTs for RCC was reviewed. The subset with in situ level II or higher caval thrombi (above renal vein) was assessed for radiographic response in thrombus size and level. Pre- and posttreatment characteristics of this population were assessed for predictors of response in height, diameter, and level of the tumor thrombi. Measurements: The main outcome measured was a change in the clinical level of tumor thrombus following TMT. We also measured radiographic responses in thrombus size and location before and after TMT. Results and limitations: Twenty-five patients met the inclusion criteria. Before TMT, thrombus level was II in 18 patients (72%), III in 5 patients (20%), and IV in 2 patients (8%). The first-line therapy was sunitinib in 12 cases; alternative TMTs were administered in 13. The median duration of therapy was two cycles (range: one to six cycles). Following TMT, 7 patients (28%) had a measurable increase in thrombus height, 7 (28%) had no change, and 11 (44%) had a decrease. One patient (4%) had an increase in thrombus-level classification, 21 (84%) had stable thrombi, and in 3 (12%) the thrombus level decreased. There was only one case (4%) where the surgical approach was potentially affected by tumor thrombus regression (level IV to III). No statistically significant predictors of tumor thrombus response to TMTs were found. Limitations include the descriptive and retrospective study design. Because TMTs were initiated according to physician and/or patient preferences, and not all patients were treated in anticipation of surgery, no conclusions could be drawn regarding selection and duration of therapy. Thus it may not be appropriate to extrapolate our experience to all patients with locally advanced RCC. Although this is the largest reported experience with in situ caval tumor thrombi treated with TMT, this series lacks sufficient statistical power to assess the usefulness of TMTs adequately in tumor thrombus cytoreduction. Conclusions: TMT had a minimal clinical effect on RCC tumor thrombi. Only patients treated with sunitinib had clinical thrombus regression; however, the clinical magnitude and relevance of this effect is not clear and should be investigated prospectively. [Copyright &y& Elsevier]

Abstract: Detailed optical and EPR analyses of states induced in dark-adapted PS II membranes by cryogenic illumination permit characterization and quantification of all pigment derived donors and acceptors, as well as optically silent (in the visible, near infrared) species which are EPR active. Near complete turnover formation of QA − is seen in all centers, but with variable efficiency, depending on the donor species. In minimally detergent-exposed PS II membranes, negligible (<5%) oxidation of chlorophyll or carotenoid centers occurs for illumination temperatures 5–20 K. An optically silent electron donor to P680+ is observed with the same decay kinetics as the S1 split signal. Cryogenic donors to P680+ seen are: (i) transient (t 1/2 ∼150 s) tyrosine related species, including ‘split signals’ (∼15% total centers), (ii) reduced cytochrome b 559 (∼30–50% centers), and (iii) an organic donor, possibly an amino acid side chain, (∼30% centers). [Copyright &y& Elsevier]

Abstract: Medications with dopamine antagonist properties, such as haloperidol, and those with serotonin reuptake inhibitor properties, such as clomipramine, have been shown to improve fluency. To examine the degree to which each of these two pharmacological mechanisms might independently affect fluency, a selective serotonin reuptake inhibitor, paroxetine, and a selective dopamine (D-2) antagonist, pimozide, were evaluated. Both types of medications also affect mood and anxiety, factors that could influence fluency levels. Therefore, we also evaluated the medications’ effects on generalized and speech-related anxiety and the relationships between changes in anxiety and changes in fluency in 11 subjects with a history of developmental stuttering. The randomized, double blind, placebo-controlled crossover study that was designed had to be terminated prior to completion due to severe side effects following withdrawal from paroxetine. Even with a reduced sample size (n =6), significant improvement in percent fluent speaking time (p =0.02) was found using a telephone task between baseline and pimozide (n =6), with average duration of dysfluencies significantly shorter (p =0.04) but no significant difference in the estimated number of dysfluencies per minute. This significant improvement was associated with non-significant increases in generalized anxiety, but non-significant decreases in speech-related anxiety. No significant differences were found in fluency between baseline and paroxetine (n =5). These preliminary results suggest that fluency improvement is more likely to be mediated by dopaminergic rather than serotonergic mechanisms. Due to its side effects, however, pimozide may be considered a risk for treatment of stuttering. Educational objectives: As a result of reading this paper the reader will describe and explain: (1) how medications may affect fluency and the rationale for selecting medications for treatment trials; (2) the interrelationship between fluency and anxiety; and (3) factors important in developing clinical trials using medications. [Copyright &y& Elsevier]

Three new analogs of UK-1 have been synthesized and their efficacies as topoisomerase II inhibitors have been determined. Results show that UK-1 and two of these analogs are catalytic inhibitors of topo II and identifies a critical structure motif necessary for enzyme inhibition. [Copyright &y& Elsevier]

Comparisons of absorption spectra of photosystem II (PSII) core complexes with those of isolated CP43, CP47 and D1/D2/cyt b559 complexes show broadenings and shifts upon disassembly of the PSII core material. Spectra of PSII cores isolated from plants and cyanobacteria reveal marked changes in energies and intensities of the sharp features associated with P680. Low-temperature, illumination-induced electrochromic shifts in PSII cores allow identification of an excitation localized on pheopytin-a (pheo a) in D1. A weak interaction between an exciton component of P680 and the D1 pheo a, both located near 684 nm, is suggested. MCD spectra of 5- and 6-chlorophyll a D1/D2/cytochrome b559 preparations provide links to photoactive pigments in intact PSII cores. [Copyright &y& Elsevier]