On a variation of the Erdős-Selfridge superelliptic curve

In a recent paper by Das, Laishram and Saradha, it was shown that if there exists a rational solution of yl=(x+1)…(x+i−1)(x+i+1)…(x+k) for i not too close to k/2 and y≠0, then logl<3k. In this paper, we extend the number of terms that can be missing in the equation and remove the condition on i

Design, Facile Synthesis and Characterization of Dichloro Substituted Chalcones and Dihydropyrazole Derivatives for Their Antifungal, Antitubercular and Antiproliferative Activities

Infectious diseases caused by fungi and mycobacteria pose an important problem for humankind. Similarly, cancer is one of the leading causes of death globally. Therefore, there is an urgent need for the development of novel agents to combat the deadly problems of cancer, tuberculosis, and also fungal infections. Hence, in the present study, we designed, synthesized, and characterized 30 compounds including 15 chalcones (2–16) and 15 dihydropyrazoles (17–31) containing dichlorophenyl moiety and also screened these compounds for their antifungal, antitubercular, and antiproliferative activities. Among these compounds, the dihydropyrazoles showed excellent antifungal and antitubercular activities whereas the chalcones exhibited promising antiproliferative activity. Among the dihydropyrazoles, compound 31 containing 2-thienyl moiety showed promising antifungal activity (MIC 5.35 µM), whereas compounds 22 and 24 containing 2,4-difluorophenyl and 4-trifluoromethyl scaffolds revealed significant antitubercular activity with the MICs of 3.96 and 3.67 µM, respectively. Compound 16 containing 2-thienyl moiety in the chalcone series showed the highest anti-proliferative activity with an IC₅₀ value of 17 ± 1 µM. The most active compounds identified through this study could be considered as starting points in the development of drugs with potential antifungal, antitubercular, and antiproliferative activities

Discordance between estimated and measured changes in plasma volume among patients with acute heart failure

Aims: In acute heart failure (AHF), changes of venous haemoglobin (Hb) concentrations, haematocrit (Hct), and estimated plasma volume (ePV) have been proposed as surrogates of decongestion. These estimates are based on the theoretical assumptions that changes of Hb concentrations and Hct are driven by the intravascular volume status and that the intravascular Hb pool remains stable. The objective of this study was to assess the relationship of changes of measured plasma volume (mPV) with changes of Hb, Hct, and ePV in AHF. Methods and results: We studied 36 AHF patients, who received two sequential assessments of mPV, measured red cell volume (mRCV) and measured total blood volume (mTBV) (48 h apart), during the course of diuretic therapy using a novel visible fluorescent injectate (VFI) technique based on the indicator dilution principle. Changes of ePV were calculated based on the Kaplan-Hakim or Strauss formula. AHF patients receiving diuretics (median intravenous furosemide equivalent 160 mg/48 h) displayed a wide range of changes of mPV (-25.4% to +37.0%). Changes in mPV were not significantly correlated with changes of Hb concentration [Pearson's r (r) = -0.241, P = 0.157], Hct (r = -0.307, P = 0.069), ePV(Kaplan-Hakim) (r = 0.228, P = 0.182), or ePV(strauss) (r = 0.237, P = 0.163). In contrast to theoretical assumptions, changes of mTBV were poorly correlated with changes of Hb concentrations and some patients displayed unanticipated variability of mRCV, suggesting an unstable intravascular red cell pool. Conclusions: Changes of Hb or Hct were not reflective of directly measured changes of intravascular volume status in AHF patients. Basing clinical assessment of decongestion on changes of Hb or Hct may misguide clinical decision-making on an individual patient level

Serum creatinine and cystatin C‐based estimates of glomerular filtration rate are misleading in acute heart failure

Aims: We aimed to test whether the endogenous filtration markers serum creatinine or cystatin C and equation-based estimates of glomerular filtration rate (GFR) based on these markers appropriately reflect changes of measured GFR in patients with acute heart failure. Methods: In this prospective cohort study of 50 hospitalized acute heart failure patients undergoing decongestive therapy, we applied an intravenous visible fluorescent injectate (VFI), consisting of a low molecular weight component to measure GFR and a high molecular weight component to correct for measured plasma volume. Thirty-eight patients had two sequential GFR measurements 48 h apart. The co-primary endpoints of the study were safety of VFI and plasma stability of the high molecular weight component. A key secondary endpoint was to compare changes in measured GFR (mGFR) to changes of serum creatinine, cystatin C and estimated GFR. Results: VFI-based GFR measurements were safe and consistent with plasma stability of the high molecular weight component and glomerular filtration of the low molecular weight component. Filtration marker-based point estimates of GFR, when compared with mGFR, provided only moderate correlation (Pearson's r, range 0.80-0.88, depending on equation used), precision (r(2), range 0.65-0.78) and accuracy (56%-74% of estimates scored within 30% of mGFR). Correlations of 48-h changes GFR estimates and changes of mGFR were significant (P 15% decrease in mGFR. Conclusions: In patients hospitalized for acute heart failure, serum creatinine- and cystatin C-based predictions performed poorly in detecting actual changes of GFR. These data challenge current clinical strategies to evaluate dynamics of kidney function in acute heart failure

A critical review of smaller state diplomacy

In The Peloponnesian War, Thucydides (1972: 402) highlights the effects of the general, overall weakness of smaller states vis-à-vis larger, more powerful ones in a key passage, where the Athenians remind the Melians that: “… since you know as well as we do that, as the world goes, right is only in question between equals in power. Meanwhile, the strong do what they can and the weak suffer what they must.” Concerns about the vulnerability of small, weak, isolated states have echoed throughout history: from Thucydides, through the review by Machiavelli (1985) of the risks of inviting great powers to intervene in domestic affairs, through 20th century US-led contemporary political science (Vital, 1971; Handel, 1990) and Commonwealth led scholarship (Commonwealth Secretariat, 1985). In the context of 20th century ‘Balkanization’, the small state could also prove unstable, even hostile and uncooperative, a situation tempting enough to invite the intrusion of more powerful neighbours: a combination, according to Brzezinski (1997: 123-124) of a power vacuum and a corollary power suction2: in the outcome, if the small state is ‘absorbed’, it would be its fault, and its destiny, in the grand scheme of things. In an excellent review of small states in the context of the global politics of development, Payne (2004: 623, 634) concludes that “vulnerabilities rather than opportunities are the most striking consequence of smallness”. It has been recently claimed that, since they cannot defend or represent themselves adequately, small states “lack real independence, which makes them suboptimal participants in the international system” (Hagalin, 2005: 1). There is however, a less notable and acknowledged but more extraordinary strand of argumentation that considers ‘the power of powerlessness’, and the ability of small states to exploit their smaller size in a variety of ways in order to achieve their intended, even if unlikely, policy outcomes. The pursuance of smaller state goals becomes paradoxically acceptable and achievable precisely because such smaller states do not have the power to leverage disputants or pursue their own agenda. A case in point concerns the smallest state of all, the Vatican, whose powers are both unique and ambiguous, but certainly not insignificant (The Economist, 2007). Smaller states have “punched above their weight” (e.g. Edis, 1991); and, intermittently, political scientists confront their “amazing intractability” (e.g. Suhrke, 1973: 508). Henry Kissinger (1982: 172) referred to this stance, with obvious contempt, as “the tyranny of the weak”3. This paper seeks a safe passage through these two, equally reductionist, propositions. It deliberately focuses first on a comparative case analysis of two, distinct ‘small state-big state’ contests drawn from the 1970s, seeking to infer and tease out the conditions that enable smaller ‘Lilliputian’ states (whether often or rarely) to beat their respective Goliaths. The discussion is then taken forward to examine whether similar tactics can work in relation to contemporary concerns with environmental vulnerability, with a focus on two other, small island states. Before that, the semiotics of ‘the small state’ need to be explored, since they are suggestive of the perceptions and expectations that are harboured by decision makers at home and abroad and which tend towards the self-fulfilling prophecy.peer-reviewe

Malignant islet-cell tumors of the pancreas

Although malignant islet-cell tumors are uncommon, they are an important group of pancreatic neoplasms because appropriate treatment can often result in effective palliation even though cure is infrequent. In general, these tumors are relatively slow growing so that a combination of surgical and chemotherapeutic measures may prove very beneficial. In some patients with tumors hypersecreting insulin, gastrin, glucagon, or vasoactive intestinal polypeptide (VIP), the hormonal effects of the neoplasm can be life-threatening. Surgical treatment must, therefore, consider both the functional and malignant characteristics of the individual tumor. In many patients with functional tumors, surgical debulking of the primary tumor may be indicated even when a curative resection cannot be accomplished. Some malignancies may be cured by an appropriate pancreatic resection even when peripancreatic lymph nodes are already involved. Although a Whipple procedure is not indicated when hepatic metastases are present, this procedure may cure tumors localized to the pancreatic head and/or peripancreatic lymph nodes. Because hepatic metastases are usually multiple and involve both lobes, liver resections, other than wedge excisions of peripherally located functional metastases, are not indicated. Malignant nonfunctioning islet-cell tumors are probably best treated with systemic or regional chemotherapy when metastatic. Surgical resections or bypass procedures may be infrequently useful in those cases in which the primary tumor causes either duodenal or bile duct obstruction. The most effective methods used to control hepatic metastases are systemic and hepatic arterial chemotherapy. An alternative is selective hepatic artery embolization. Recently, an implantable hepatic arterial infusion pump has been used with encouraging results in this group of patients. The chemotherapeutic agents that have been most effective in the treatment of hepatic metastases include streptozotocin, DTIC, and fluorouracil . Les tumeurs insulaires malignes sont rares mais elles présentent un grand intérêt car si le traitement entraîne exceptionnellement leur guérison il assure une survie des malades qui en sont porteurs. Ce sont en effet des tumeurs malignes à développement lent, sensibles à l'action de l'association de la chimiothérapie et de la chirurgie. Chez certains sujets les tumeurs secrétant de l'insuline, de la gastrine, du glucagon, du V.I.P. peuvent mettre en jeu la vie du malade sous l'effet de l'hypersecrétion hormonale. Le traitement chirurgical dépend de ce fait, des caractères fonctionnels et du degré de malignité de chaque type de tumeur. En présence de lésions hypersecrétantes l'exérèse de la tumeur primitive doit être envisagée alors même que la possibilité d'obtenir une guérison définitive ne peut être escomptée. Il est aussi à noter que certaines lésions malignes ont été traitées avec succès alors que les ganglions lymphatiques correspondants étaient déjà envahis. Si l'opération est contre-indiquée en présence de métastases hépatiques la duodénopancréatectomie céphalique s'applique aux tumeurs insulaires céphaliques qu'elles s'accompagnent ou non d'un envahissement des ganglions juxta-pancréatiques. Du fait que les métastases hépatiques sont souvent multiples et qu'elles intéressent les deux lobes l'action sur le foie se limite à l'éxérèse des métastases accessibles à la résection hépatique segmentaire. Les tumeurs insulaires malignes qui ne sont pas hypersecrétantes relèvent de la chimiothérapie par voie générale ou de la chimiothérapie régionale dès lors qu'elles s'accompagnent de métastases. C'est seulement lorsque ces lésions entraînent une obstruction de la voie biliaire principale ou du duodénum que la résection ou les anastomoses de dérivation sont indiquées. La chimiothérapie par voie générale ou par la voie de l'artère hépatique ou encore l'embolisation de cette dernière représentent les meilleures méthodes de traitement des métastases hépatiques. L'emploi récent de pompes à infusion de l'artère hépatique a donné des résultats intéressants chez ces malades. Les agents chimiques les plus efficaces sont la streptozotocine, le DTIC et le Fluorouracil. Aunque los tumores malignos de células insulares del páncreas son raros, éstos constituyen un grupo importante entre las neoplasias pancreáticas por cuanto el tratamiento apropiado con frecuencia resulta en una paliación efectiva a pesar de que la curación sea poco frecuente. En general estos tumores son de crecimiento lento y la combinación de la cirugía con quimioterapia puede llegar a ser beneficiosa. En algunos pacientes con tumores que hipersecretan insulina, gastrina, glucagón o VIP (polipéptido vasoactivo intestinal), los efectos hormonales del neoplasma pueden poner en peligro la vida. Por ello el tratamiento quirúrgico debe considerar tanto las caracteristicas funcionales como las de malignidad de cada tumor en particular. En muchos pacientes con neoplasmas funcionantes, el debultamiento quirúrgico del tumor primario puede estar indicado cuando la resección curativa no es realizable. Algunas neoplasias malignas pueden ser curadas mediante una resección pancreática adecuada a pesar de que los ganglios linfáticos peripancreáticos ya se hallen afectados. Aún cuando el procedimiento de Whipple no esta indicado en presencia de metástasis hepáticas, esta operación puede curar tumores localizados en la cabeza del páncreas y/o en los ganglios linfáticos peripancreáticos. Debido a que las metástasis hepáticas generalmente son múlitples y afectan a ambos lóbulos, las resecciones hepáticas, diferentes de las resecciones en cuña para lesiones funcionantes localizadas en la periferie del higado no están indicadas. Los tumores malignos no funcionantes de células insulares probablemente deben ser tratadas con quimioterapia sistémica o regional cuando se encuentren en fase metastásica. Las resecciones quirúrgicas o los procedimientos derivativos infrecuentemente son de utilidad en aquellos casos en los cuales el tumor primario causa obstrucción duodenal o del conducto biliar. Los métodos de mayor efectividad en el control de las metéstasis hepáticas son los de quimioterapia sistémica y arterial hepática. Una alternativa es la embolización selectiva de la arteria hepática. Recientemente ha venido a ser utilizada una bomba implantable de infusión arterial heptica con resultados halagadores en este grupo de pacientes. Los agentes quimioterapéuticos que han probado ser de mayor efectividad en el tratamiento de las metástasis hepáticas incluyen la estreptozotocina, la dimetiltrizenoimidazol carboxamida (DTIC) y el Fluorouracilo.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/41316/1/268_2005_Article_BF01656036.pd

Assessing the field of science and religion: advice from the next generation

© 2017 by the Joint Publication Board of Zygon The field of science and religion is undergoing a transition today requiring assessment of its past movements and identifying its future trajectories by the next generation of science and religion scholars. This essay provides such assessment and advice. To focus efforts on the past, I turn to Ian Barbour's own stock taking of the field some forty years ago in an essay entitled “Science and Religion Today” before giving some personal comments where I argue that much of the field has traditionally focused on the conversation between Christianity and the natural sciences. At present, however, we are beginning to see that the future of the conversation lies beyond the dialogue between the natural sciences and Christianity. I suggest that the future dialogue will and ought to expand in several directions: (1) into non-Christian religions and theology, (2) into the human sciences, (3) into science and technology Studies, and (4) into the humanities more broadly