More than of the BRAF mutations in

More than 90% of the BRAF mutations in human malignantmelanomas involve THZ531 600, and 80% of these mutations are comprised of the V600E mutation. Nevertheless, V600K is the second most common mutation, constituting 14–28% of the BRAF mutations that underlie melanoma (Forschner et al., 2013). From one recent study, three novel mutations in exon 11 of BRAF—G442S, W450Stop and I457T—have been identified in melanoma (acral and mucosal) in addition to the eight previously reported mutations in exon 11 and 15: G466R, D594E, D594G, V600E, V600K, K601E, W604Stop and S616F (Si et al., 1990).
From the literature, the BRAF protein has three AKT phosphorylation sites: Thr439, Ser428 and Ser364. In vitro substitution of the Thr439 residue with an Ala residue leads to BRAF activation through the loss of AKT-induced inhibition of RAF1 phosphorylation. Hence, the detection of K438T and K438Q in melanoma, similar to Thr439, is likely to inhibit AKT-dependent phosphorylation (Brose et al., 2002). Similarly, the presence of Ser428, Ser364 and the aforementioned novel mutations (G442S, W450Stop and I457T) (Si et al., 1990) in the vicinity of Thr439 are suggested to play a role in tumourigenesis (Brose et al., 2002).

During the past few years, patients with epithelial ovarian cancer have been treated identically in clinical trials and in pathological practise (Gershenson, 2013). The development of a 2-tier system for serous carcinomas, with low and high grades, is now generally accepted (Kohn and Hurteau, 2013). This simple approach, which is based on biological evidence, proposes that both tumours develop through different pathways. With infrequent mitotic figures, low-grade serous carcinomas, such as invasive micropapillary serous carcinoma (MPSC), show low-grade nuclei and are believed to evolve from adenofibromas or cystadenomas, which are borderline in the tumour-serous carcinoma sequence, via mutation in the KRAS, BRAF, or ERBB2 genes (Vang et al., 2009). Mutations in the KRAS, BRAF, or ERBB2 genes result in the upregulation of MAPK, which in turn regulates uncontrolled proliferation in atypical proliferative serous tumours (APST). Serous cystadenomas found adjacent to APSTs have been found to have identical KRAS or BRAF mutations, suggesting that the presence of APSTs near the cystadenomas may support the regulation of serous carcinomas (Vang et al., 2009).
While BRAF V600E has been reported to be prevalent in 33% of tumours in the past, recent findings exhibited only 2% low-grade serous mutations (Ziai and Hui, 2012). Conversely, in low-grade ovarian serous carcinoma patients, the correlation between BRAF and KRAS has not yet been explored. Additionally, unlike previous findings, one report discussed the low frequency characterisation of KRAS and BRAF mutations in advanced stage low-grade serous carcinomas (Wong et al., 2010). Recently, 20–40% of low-grade serous carcinomas have been characterised with KRAS mutations, while BRAF mutations are found in approximately 5% of this subtype (Gershenson, 2013). In the literature, most of the BRAF mutations have been identified using DNA-based techniques; however, Bösmüller et al. differentiated the BRAF V600E mutation using mutation-specific monoclonal antibody (VE1) specific for the BRAF V600E. This ability to immunostain the BRAF V600E mutant protein in serous ovarian tumour samples with low epithelial content demonstrates the practical usefulness of mutation-specific recognition by an antibody (VE1) (Bosmuller et al., 2013).

Prostate cancer, the most common cancer type in Western Europe and USA, has variable incidence of BRAF and/or KRAS mutations among different races (Ren et al., 2012; Shen et al., 2010). Three reports have recorded BRAF mutations in prostate carcinomas, and one of these showed no BRAF mutations in the American and German populations. However, 10.2% of prostate carcinomas have been identified as having BRAF mutations in the Korean population (Cho et al., 2006). In addition, 10% of prostate cancer cases have been characterised as having an activating BRAF mutation in the Asian population (Kollermann et al., 2010). This difference in BRAF mutation frequency has been characterised in many different ethnic backgrounds. According to recent evidence, a gain in the RAF gene copy number resulted in the activation of the RAS/RAF/MEK/ERK pathway was found to be the main contributing element in the regulation of prostate cancer in a Chinese population (Ren et al., 2012). However, in another report of Chinese patients, KRAS mutations at codons 12 and 13 were found in prostate cancer patients while no BRAF mutation was observed at codon 600 (Shen et al., 2010). Caucasian patients had results similar to the Chinese patients, suggesting that BRAF mutations are rarely found in prostate cancer and are not connected with tumour progression. Nevertheless, recurrent gene fusions have shown that the SLC45A3-BRAF and ESRP1-RAF1 fusions drive the molecular events occurring in advanced prostate and gastric cancers, as well as melanoma (Palanisamy et al., 2010). Subsequently, Kollermann et al. have argued that the emergence and the increased usage of BRAF-targeted therapies may have limited efficacy in treating prostate cancer patients (Kollermann et al., 2010).

The contribution of marine and or brackish

The contribution of marine and/or brackish species to the fish assemblage was high and accounted for 33% of the total number of species. Their presence was more conspicuous downstream. This invasion of marine or brackish species in freshwater could be explained by the fact that such species have specialized gills and other adaptations that allow rapid regulation of ion exchange when moving between habitats (Carol and Michael, 1999). Also, marine and/or brackish species in freshwater could play an important role in the structuring of fish communities and equilibrate food chain (Leung and Camargo, 2005). Their presence in freshwater could also be related to feeding, spawning, nursery, growth and to avoid predators.
The beta indices calculated between upper, middle et lower course indicated no significant differences in the species composition but it was very high (0.79) into the middle and lower area. These analyses showed a relatively homogeneous and similitude ichthyofauna in different areas of the stream, characterized by the dominance of Alestidae, Schilbeidae, Cichlidae and Cyprinidae families. These observations were made on other Rivers such as Bandama (Lévêque et al., 1983), Ehania (Konan et al., 2013) in Côte d’Ivoire.
Understanding the factors that influence fish guanylyl cyclase structure is important not only for accumulating basic information, but also to predict the effects of environmental change on the integrity of these communities (Súarez et al., 2004). Dead wood leaf roots; electrical conductivity, total dissolved solids, mud, nitrite, basin width, dissolved oxygen and pH were the most important factors in describing fish assemblage structure in the Nero River. Hydrological characteristics and morphology of the hydrosystems can be considered as factors in structuring biological communities they harbour (Pourriot and Meybeck, 1995). Thus, the nature of the substrate is an important ecological factor for fish communities. Indeed, the Catfish Family Clariidae (eg., H. isopterus, H. longifilis and C. anguillaris) and others species such as H. fasciatus and P. obscura, are known to be resistant and had light level of ecological tolerance index (ETI). Therefore, these species are more abundant in the waters composed by mud substrate in which dissolved oxygen is low and nitrite is high. By opposite, the less resistant species to dissolved oxygen (eg., B. ablabes, A. atesuensis and B. trispilos) with high tolerance level (), will prefer the substrates of sand. In addition, the influence of the width on the species was noted in this study. Indeed, (P. bovei, B. ablabes, and E. chaperi) are known to be specie of small size (Fishbase, 2003). Also, these species will prefer tributaries to avoid River mainstream predators and the water velocity of the mainstream. Our results seem to indicate that total dissolved solids (TDS) have significant influence on the distribution of some species (eg., E. dageti, Poropanchax rancureli, C. anguillaris and P. bovei). These observations were in agreement with those of Da Costa et al. (2000). According to these authors, total dissolved solids (TDS) and conductivity were some of the most discriminating factors in the Agnéby and the Bia Rivers (Côte d’Ivoire).

Conclusion and management implications

Authors wish to express their sincere thanks to the staff of Hydrobiology Laboratory of University Felix Houphouët Boigny (Côte d’Ivoire) for fieldwork assistance, and to the Belgian Technical Cooperation for providing financial support through the project entitled characterization, utilization and conservation of Côte d’Ivoire freshwaters fish diversity.

As sessile organisms plants are frequently encountered by many environmental stresses including abiotic as well as biotic resulting in altered plant growth and metabolism. Salinity is one of the important abiotic environmental factors having great effects on plant growth and development (Barnawal et al., 2014). Increased industrialization and use of saline water for irrigation purposes causes conversion of fertile soils into salt affected soils making the situation much graver. It has been estimated that around 5% to 7% of global land is salt affected (Ruiz-Lozano et al., 2012). This increase in soil salinity induces osmotic stress resulting in altered growth and physiology. Several physio-biochemical processes including photosynthesis, respiration, nitrogen metabolism and ion homeostasis are affected adversely by salinity (Tejera et al., 2004; Porcel et al., 2012).

Z-YVAD-FMK The measured amounts of salicylic acid loaded

The measured amounts of salicylic Z-YVAD-FMK loaded in KPAsp, KPAsp/CMCTS semi-IPN and KPAsp/CMCTS IPN hydrogels were 36.69mg/g, 54.36mg/g and 72.07mg/g, respectively. The more amounts of salicylic acid loaded in the KPAsp/CMCTS IPN hydrogel attributed to the introduction of hydrophilic groups (–OH, –COOH and –NH2) and the increase of an effective network structure of the IPN hydrogel. Moreover, the increased porous structure could also enhance the diffusion of the drug into the hydrogel network.
The release profiles of salicylic acid from KPAsp, KPAsp/CMCTS semi-IPN and KPAsp/CMCTS IPN hydrogels were tested at pH values of 1.2 (simulated gastric fluid) and 7.4 (simulated intestinal fluid) at 37°C. As could be seen from Fig. 11, the release behaviors of salicylic acid from the prepared hydrogels are distinctly pH- responsible. The drug release of each hydrogel at pH values of 1.2 was obviously slower than that at pH values of 7.4. And the release rate of salicylic acid from the KPAsp/CMCTS IPN hydrogel is always the highest among the three hydrogels, which should be related to the IPN structure with increased porous structure and specific surface area. At pH 1.2 and 7.4, the corresponding cumulative amounts of salicylic acid released from the KPAsp/CMCTS IPN hydrogel were 36.9% and 62.1%, respectively. That may be ascribed as follows: Firstly, in acid environment carboxy groups on the hydrogel are in the form of –COOH, as the addition of CMCTS, –OH on the hydrogel increased, the effect of H-bonding between these –COOH and –OH limits the release of salicylic acid. Secondly, as the pH value increases, carboxy groups on the IPN hydrogel are inclined to form –COONa, the effect of H-bonding between –COOH and –OH recedes, therefore salicylic acid become easy to release from the hydrogel. Thirdly, the higher swelling ratio at the condition of pH=7.4 than at pH=1.2 is of benefit to drug release. In conclusion, this novel IPN hydrogel can control drug release by external surrounding stimuli and has a relative high drug release rate in simulated intestinal fluid. This would be suitable in the design and development of intestinal drug delivery systems.
A biodegradable KPAsp/CMCTS IPN hydrogel was successfully synthesized in an aqueous system using a simple one-step method. The swelling ratio, pH, temperature and salt sensitivities, drug-loaded characteristics of the KPAsp, KPAsp/CMCTS semi-IPN and KPAsp/CMCTS IPN hydrogels were investigated. The results revealed that the introduction of IPN significantly improved all the capacities of hydrogels. The maximum swelling ratio of the IPN hydrogel was 98.1g/g in physiological saline and 306.7g/g distilled water which showed 2 times and 70% enhancement in comparison with that of the KPAsp hydrogel. The drug controlled release properties of the prepared hydrogels were evaluated and results indicated that prepared hydrogels could control drug release by external surrounding stimuli. The drug controlled release properties of KPAsp/CMCTS IPN hydrogels is the most outstanding, and the correlative measured release profiles of salicylic acid at 37°C were 36.9wt% in pH=1.2 (simulated gastric fluid) and 62.1wt% in pH=7.4 (simulated intestinal fluid) respectively. These studies would be exploited in the design and preparation of suitable drug delivery systems.


This work was financially supported by the Natural Science Foundation of China (Grant No. 21304066) and Scientific and Technological Projects in Shanxi Province (Grant No. 20100311117).

The volume of sewage water generated by domestic, industrial and commercial sources has increased along with the increasing population, urbanization, improved living conditions, and economic development (Qadir et al., 2010). In the urban areas of many (developing) countries, urban and peri-urban agriculture depends, at least to a certain extent, on sewage water as a source of irrigation water. The quality of water and the conditions under which this water is used vary significantly. In poor countries, this water may, in extreme cases, take the form of diluted raw sewage, even if this practice is considered illegal (Huibers et al., 2004). However, the quality of the wastewater used and the nature of its use vary enormously, both between and within countries. In many low-income countries in Africa, Asia and Latin America, the wastewater tends to be untreated, whereas in middle-income countries, such as Tunisia and Jordan, treated wastewater is used (Al-Nakshabandi et al., 1997; Qadir et al., 2010).

Thioacetamide TAA is a potent experimental hepatotoxin and hepato

Thioacetamide (TAA) is a potent experimental hepatotoxin and hepato-carcinogenic compound; therefore, it is used often to induce fulminant hepatic failure in experimental animal models (Sarkar and Sil, 2007). Additionally, the influences of TAA are not limited to the liver as profound structural and functional changes have been described in the kidney, spleen, lung, intestine, stomach and guanabenz (Al-Bader et al., 2000; Liu et al., 2000; Caballero et al., 2001; Avraham et al., 2009; Latha et al., 2003; Kadir et al., 2013; Gao et al., 2014). Moreover, the toxic influences of TAA depend on several factors such as its concentration, number of doses, administration period, administration methods, animal’s gender, strain, age, weight and physiological case.
Medicinal plants play an important role in pharmacology and medicine for many years. Today, it is estimated that about 80% of the world population relies on botanical preparations as medicine to meet their health needs (Ogbera et al., 2010). Apart from currently available therapeutic options, many herbal medicines have been recommended for the treatment of many diseases. Medicinal plants and herbal drugs are prescribed widely because of their effectiveness, less side effects and relatively low cost (Venkatesh et al., 2003; Tohidi et al., 2011). Therefore investigation on some active principles from traditional medicinal plants has become more important (Suba et al., 2004). Furthermore, in different countries many herbs are used in folk medicine to treat drug or toxin induced renal damage (Palani et al., 2009). The olive tree and in particular its leaves have been used for the treatment of wounds, fever, diabetes, gout, atherosclerosis and hypertension since ancient times (Jänicke et al., 2003). Olive leaves are considered a cheap raw material and a useful source of high-added value products (Briante et al., 2002; Jemai et al., 2008). Different studies have shown that olive leaves extracts and their constituents possess a wide range of pharmacologic and health promoting properties including antiarrhythmic, spasmolytic, immune-stimulant, and liver, kidney and heart protective effects. Moreover, anti-atherosclerotic, hypotensive, anti-inflammatory, antioxidant, anti-thrombic and hypoglycemic effects were reported (Visioli et al., 1998; Andrikopoulos et al., 2002; Wang et al., 2008; Wainstein et al., 2012; Kumral et al., 2015). The natural forests of Saudi Arabia spread along the Western mountainous area from North to South. Juniper trees represent more than 90% of these forests (Abo-Hassan et al., 1984). Juniperus is a unique genus from the family Cupressaceae. The genus Juniperus consists of approximately 68 species (Seca and Silva, 2006; Adams, 2011). In traditional medicine, Juniperus species are used as remedies against the common cold, urinary infections, urticaria, dysentery, hemorrhage, and rheumatic arthritis and to relieve menstrual pain worldwide (Seca and Silva, 2006). Therefore, the objective of the present study was to evaluate the possible protective influences of olive (Olea oleaster) and juniper (Juniperus procera) leaves extract against TAA-induced nephrotoxicity in male mice.

Materials and methods

Levels of serum creatinine, BUN and uric acid in control, TAA, TAA plus olive leaves extract, TAA plus juniper leaves extract, TAA plus olive and juniper leaves extracts, olive leaves extract, juniper leaves extract, and olive and juniper leaves extracts treated mice after six and twelve weeks are shown in Table 1. After six weeks, the level of serum creatinine was significantly unchanged in all treated groups compared with the control group. In comparison with control data, levels of serum BUN (+26.3%) and uric acid (+24.0%) were significantly raised in mice treated with TAA. Insignificant changes of serum BUN and uric acid levels were noted in TAA plus olive leaves extract, TAA plus juniper leaves extract, TAA plus olive and juniper leaves extracts, olive leaves extract, juniper leaves extract, and olive and juniper leaves extracts treated mice as compared with control mice. After twelve weeks, levels of serum creatinine (+38.5%), BUN (+26.3%) and uric acid (+24.0%) were markedly elevated in mice treated with TAA compared to control mice. There were no significant changes in levels of serum creatinine, BUN and uric acid in TAA plus olive leaves extract, TAA plus juniper leaves extract, TAA plus olive and juniper leaves extracts, olive leaves extract, juniper leaves extract, and olive and juniper leaves extracts treated mice (Table 1).

Bleomycin Sulfate Also the length of hours on duty is a key

Also the length of hours on duty is a key factor for fatigue-related accidents, as reported by three studies which examined trends in national accident statistics. An aggregated analysis of several studies carried out in English industries [18] showed an almost exponential increase of accidents after the eighth hour of work; this has also been evidenced in Sweden [19], based on examination of the national database of work accidents, and in Germany through the insurance registries on industrial accidents [20]. According to these studies, it is possible to estimate double the risk of accident when working in a12-h shift as compared with an 8-h shift. Also, a recent survey of more than 75,000 US workers over a 4-year Bleomycin Sulfate [21] confirmed a higher risk of injury strictly related to a progressive increase of working hours and reduction of sleep duration.
Besides industry, the transport sector is particularly sensitive to such problems. Many studies carried out in the last decades have evidenced how drowsiness and fatigue are key risk factors in road and railway accidents of professional drivers [22,23].
Accidents caused by driver fatigue or lapses of attention due to sleep deprivation are often quite severe as the drowsy and/or fatigued driver may not take the appropriate actions to avoid an accident. It was also reported that sleepy drivers often do not perceive their risky condition and frequently drive with closed eyes for 5 to 50 second periods (microsleep) [24-26].
It was found that being sleepy while driving increases the risk of a serious injury crash by eight-fold [27]. Moreover, several studies showed that “single vehicle” accidents on roads have the greatest probability of occurring at night or in the early morning, even when traffic density has been controlled for [28-31]. Similar findings also come from studies on train drivers [32-34].
Härmä et al. [33] recorded severe sleepiness in 50% of the night shifts and in 15-20% of the morning shifts of Finnish train drivers and railway traffic controllers. The risk of severe sleepiness was 6-14 times higher in the night shift and about twice as high in the morning shift as compared with the day shift.

Health Disorders

Social Problems
Shift work also has a relevant interference on family and social life, which may result in psychological stress and psychosomatic disorders [76].
Time pressure and work/family conflicts are common problems, particularly for those who have high family burdens or complementary duties (i.e. women with small children), and this may also have a negative influence on marital relationships, parental roles and children’s education in addition to the increasing sleep problems, chronic fatigue, and psychosomatic complaints [77-79].

Inter-individual Differences in Tolerance
There is a high inter-individual variability in tolerance to shift work, which can be due to the interaction among individual characteristics, social conditions, and working conditions [80].
Despite several epidemiological studies concerning health troubles and disorders associated with shift and night work, it is not possible to identify some individual characteristics that can be profitably used as predictors of good or scarce tolerance to shift work. Among these characteristics, some authors suggested looking at morningness/eveningness, neuroticism, rigidity/flexibility of sleeping habits, hardiness, and stability of circadian rhythms [81-83].
Besides, good physical fitness increases tolerance by lessening fatigue and improving recovery mechanisms [84].
Certainly ageing may be a key factor of tolerance to shift and night work in relation to the associated physiological and physio-pathological changes occurring during the working life, particularly with regards to sleep length and quality, earlier phasing of circadian rhythms, and higher proneness to circadian desynchronization of biological rhythms [84-86].
Moreover, less favourable living and social conditions, often reported by surveys in developing countries, and usually associated with poor working conditions and long working hours, may aggravate the impact of shift work on health [87-89].

A significant improvement in mouth opening was attained in

A significant improvement in fiin opening was attained in both groups across the study period. This improvement was significant after 1 or 2months of treatment in the soft or hard splint group, respectively. These results are comparable to those of Suvinen and Reade (1989), who reported a 7.4-mm increase in jaw opening after splint therapy. The early improvement in mouth opening observed with the soft splint therapy might be due to the material resiliency, which helped to distribute the heavy functional occlusal forces and hastened relief from muscle spasms. This resiliency could also underlie the early relief from masticatory muscle tenderness compared to the hard splint group. Nevertheless, both splint therapies alleviated the pain and tenderness of the TMJ and muscles, leading to an increase in maximal jaw opening. This result is in accordance with Block et al. (1978), who concluded that almost 74% of patients with TMDs had complete remission of symptoms after 6weeks of occlusal splint therapy.
The early improvement in TMJ clicking observed with hard splint therapy might be due to the wider TMJ space created by the hard occlusal splint. The increased TMJ space allows the meniscus to return to its original position with ease, thus reducing the chance for clicking. The improvement in TMJ clicking and alleviation of tenderness in the TMJ and masticatory muscles observed in this study are in agreement with Kovaleski (1975), who reported improvements in TMJ clicking and tenderness after 2months of occlusal splint therapy. Another study reported that 87% of patients showed a reduction in pain, 50% showed a reduction in VAS scores, and 70% had no clicking after splint therapy (Tsuga et al., 1989). In another study, soft splint therapy reduced facial myalgia and TMJ clicking by 74% (Harkins et al., 1988). These improvements can be attributed to the even intensity of contacts among all teeth, with disocclusion of the posterior teeth and condylar guidance in all movements. These conditions lead to a relaxation of the elevator and positioning muscles and contribute to reduce the abnormal muscle hyperactivity (Boero, 1989).
Occlusal splint insertion alters the resting position, and adapting to this new position increases the occlusal vertical dimension beyond the free space. The new resting position allows muscles to function more efficiently during contact and reduces muscle activities during postural functions. Meanwhile, the increase in the vertical dimension decreases the muscular effort required, resulting in relaxation of the muscles and TMJ (Mona et al., 2004). The findings of the present study are in agreement with those of Naikmasur et al. (2008). These authors compared the use of a soft occlusal splint with muscle relaxants and analgesics in the management of MPD, and concluded that occlusal splint therapy was superior to pharmacological treatment in terms of improving pain, muscle tenderness, and TMJ clicking. From findings obtained by electromyography of the masticatory muscles, Daif Emad (2012) concluded that occlusal splint therapy for MPD improves the signs and symptoms of TMD. Our findings support their results, revealing that occlusal splint therapy is a conservative treatment modality that is beneficial for reducing pain and muscle tenderness and for improving jaw opening.


Ethics statement

Conflict of interest

Disclosure of funding

Mineral trioxide aggregate (MTA) has many favorable biological properties for endodontic usage (Torabinejad and Parirokh, 2010). These properties are related to the formation of calcium hydroxide and subsequent release of calcium ions by MTA, as these actions modulate cytokine production and promote an alkaline pH, hydroxyapatite formation, and cementum deposition (Sarkar et al., 2005; Torabinejad et al., 1997; Zarrabi et al., 2010). However, despite these favorable properties, MTA has several drawbacks, including a prolonged setting time and difficult handling characteristics (Torabinejad et al., 1995). In this regard, the addition of accelerators and other vehicles to MTA has been recommended (Bortoluzzi et al., 2006; Gandolfi et al., 2008; Kogan et al., 2006; Wiltbank et al., 2007).

neuropeptide receptors En t rminos generales puede apreciarse que los

En términos generales puede apreciarse que los mayas prehispánicos aprovechaban la carne y éste es uno de los rasgos que unen el área maya en general y que se mencionaron al principio de esta publicación. La postulada dieta tradicional maya es semejante en toda el área, a pesar de hallarse diferencias entre las distintas regiones geográficas en cuanto a la alimentación, que parecen estar relacionadas con las condiciones ambientales, o bien, con los patrones culturales que prefirieron o prohibieron ciertos taxa. En tiempos prehispánicos existía un movimiento de bienes que incluía a determinados animales, como el intercambio de pescados de la costa a sitios tierra adentro y de animales de tierra adentro a la costa, pero tal vez este comercio se mantuvo a pequeña escala por falta de métodos para conservar la carne por un largo tiempo, lo que hubiera requerido el transporte de alimentos frescos a larga distancia. Una discusión detallada sobre el tema, que presenta resultados del comercio a corta distancia en la zona del Petexbatún, Guatemala, puede encontrarse en Thornton (2011).

El sistema milpero y la caza de animales
Los datos zooarqueológicos que se han expuesto en la sección anterior podrían utilizarse para interpretar no solamente la dieta, sino los particulares modos de obtención de la neuropeptide receptors vertebrada que seguían los mayas precolombinos. Un rasgo notable que caracteriza a muchos pueblos mesoamericanos en general y los mayas en particular es el poco uso de animales domésticos en la dieta, mientras que las plantas domésticas ocupaban un lugar preferencial en el sustento diario (véase Valadez 2003). En este sentido se observan diferencias fuertes con muchos de los pueblos prehistóricos e históricos del Viejo Mundo, de Sudamérica y de Asia, en los que la domesticación de animales desempeñaba un papel preponderante (Davis 1989; Gautier 1990). Cabe la posibilidad de interpretar los panoramas taxonómicos del área maya como formas de manejo faunístico muy específico, que puedan relacionarse con esta particularidad cultural (véase Götz 2012c).
Se ha constatado que la fauna aprovechada en los sitios costeros precolombinos de Yucatán es taxonómicamente más variada que en los sitios tierra adentro de la misma región, presentándose en los primeros una amplia gama de peces, tortugas y aves marinas, así como mamíferos acuáticos (Götz 2008). En los sitios tierra adentro prevalece una baja diversidad faunística, con énfasis en los artiodáctilos, aves de tierra y pocos reptiles. Omnipresente en la gran mayoría de los contextos, en especial en las Tierras Bajas mayas del norte, son los restos de perro doméstico, pecarí de collar, venado cola blanca, venado temazate, pavo de monte e iguana negra, especies silvestres cuyo requerimiento ecológico está relacionado con bosques secundarios y espacios agriculturales abiertos. Por otro lado, las muestras de restos arqueofaunísticos acumulados en contextos identificados como basureros de los sitios tierra adentro carecen frecuentemente de especies que prefieren bosques profundos, como los felinos (Panthera onca, Leopardus pardalis, Leopardus wiedii, etc.), pecarí de labios blancos (Tayassu pecari), venado temazate y hocofaisán (véanse, entre otros, Howell y Webb 2004; Leopold 2000; ; Reid 1997; Terán y Rassmussen 1994).
Parece que los taxa que constituyeron la dieta maya precolombina pudieran explicarse retomando el concepto –no el perfil taxonómico– de cacería en jardines, que ha descrito inicialmente Olga Linares (1976) para Panamá y que los ecólogos Barrera-Bassols y Toledo (2005) aplicaron a bulbourethral glands la cacería campesina moderna del área maya (para una discusión detallada véase Götz 2012c). Este esquema encaja muy bien en el perfil faunístico observado por medio de los hallazgos zooarqueológicos, por lo que podría afirmarse que este sistema fue practicado también en la antigüedad en el área maya (véase también Carr 1995; Shaw 1999). Según Barrera-Bassols y Toledo (2005), los mayas yucatecos actuales obtienen la mayoría de la presa faunística silvestre mediante cacerías en los horticultivos adyacentes a los asentamientos, en las milpas y en los bosques secundarios, formados intencionalmente mediante el sistema rotativo de la milpa. Este sistema ocasiona, a través del uso de la técnica de la roza, tumba y quema, que las zonas en las que se practica el cultivo de la milpa se conviertan en un mosaico de bosques secundarios –áreas de barbecho– y espacios agriculturales (Eastmond y Faust 2006: 272; Hostettler 1996: 292; Terán y Rassmussen 1994: 278).

Otros de los males que tratan y

Otros de los males que tratan, y cuya presencia es común en la vida cotidiana e implica en ocasiones la asistencia de un ritualista, serán descritos trifluoperazine hydrochloride continuación con más detalle.

Por un lado, sus propias bases hacen referencia a un nivel específico de la organización social: el espacio inmediato del hogar o la familia extensa que se abre para incluir las relaciones de compadrazgo o el ámbito vecinal. Sumodusoperandi pareciera enfatizar las relaciones sociales, sus interacciones y la participación y dimensión colectiva del proceso de curación. Se trata de un proceso sutilmente ordenado (en ocasiones jerarquizado), con frecuencia centralizado en la figura de la madre, pero a menudo también constituido por una intervención diferencial de personas, especialmente mujeres pertenecientes a diversas generaciones, aunque también hombres y niños, que se desenvuelven en su contexto y en su espacio original: madres de familia, abuelas maternas o paternas, ciertos parientes rituales —madrinas—, vecinas experimentadas que actúan como asistentes o terapeutas, y otras categorías de participantes, como sacerdotes, hijos de vecinos o los propios vecinos anfitriones, en el caso de la tiricia (paradigmático en el sentido de la intervención acumulativa y colectiva). Existe una dimensión fuertemente social, en la que las secuencias y tiempos de la curación suelen encontrarse en relación con personas distintas y con la convergencia de sus acciones combinadas sobre el niño enfermo. En este sentido, en el campo de las afecciones infantiles, el lenguaje sobre la terapéutica muchas veces atañe directamente al campo de las relaciones sociales, en tanto discurso de la etiología nosológica, en el que las causas de los males son vinculados en buena medida con distintos tipos de relación social: la envidia o deseo ajeno (en el mal de ojo), el exceso de juego e interacción con los adultos (en la caída de mollera) o el estado opuesto: la soledad o ausencia de compañía (en la tiricia).


La Costa Chica de Oaxaca. Antecedentes históricos y situación actual
La llegada de los colonizadores españoles a lo que hoy conocemos como territorio mexicano trajo consigo cambios significativos en materia demográfica. La aparición de enfermedades desconocidas para la población nativa de estas tierras aumentó el índice de mortalidad. Otro factor que influyó de manera decisiva en el descenso demográfico fue la inserción de los indígenas como trabajadores en las encomiendas y los repartimientos.
Lo anterior tuvo como resultado la necesidad de incorporar mano de obra que sustituyera en las actividades económicas novohispanas las cuantiosas bajas entre los colonizados. Los seleccionados para cubrir este déficit poblacional fueron los esclavos africanos. Con la expansión colonial europea, la trata de esclavos constituyó un negocio próspero que servía como paliativo ante la insuficiencia de mano de obra en las colonias. Sin embargo, los embarques debían pasar por Europa para registrar las cargas y pagar el impuesto correspondiente. Dado el elevado costo de este tipo de transacciones, los comerciantes crearon la ruta directa de África hacia los principales puertos americanos (Martínez, 2010: 28), de tal manera que los primeros africanos llegaron directamente del lejano continente.
Más adelante, otros esclavos arribaron con sus amos españoles en calidad de siervos o criados domésticos (Meza, 2003). La economía colonial española fundamentada principalmente en la minería, hizo necesario una mayor importación de mano de obra, la cual provenía tanto de España como de Portugal, así como de la región caribeña. De acuerdo con los estudios historiográficos, se tiene registrado el ingreso de alrededor de 200 000 africanos a la Nueva España (Velázquez 2005:29).
Si bien la presencia de los africanos se diversificó en los diferentes puntos geográficos del territorio novohispano, fueron cuatro las zonas donde su presencia fue más significativa: en la región del Golfo, con Veracruz como centro rector; en el norte y oeste de la ciudad de México; por Puebla hacia la costa del Pacífico (Acapulco) y, principalmente, la ciudad y el valle de México (Davidson, 1981: 81). La mano de obra de origen africano se instauró en los ingenios azucareros, la ganadería, obrajes y agricultura de cacao, pero también como trabajadores urbanos en diferentes oficios, como sastres, zapateros y pintores.

br Role of Funding Source This work was supported

Role of Funding Source
This work was supported by NIMH grant R01MH093439 to the first author.


Conflict of Interest


A significant limitation of single nucleotide polymorphism (SNP) association studies is that testing efficiency is affected by the number of SNPs analyzed and sample size. SNP association is also influenced by hydralazine hcl and risk allele frequency (Bhangale et al., 2008; Zondervan and Cardon, 2004). Selection of the most informative SNPs may help maximize power of common variants in association with phenotypes (Hinds et al., 2005). However, schizophrenia is characterized by significant genetic heterogeneity (Hallmayer et al., 2005; Owen et al., 2005; Sebat et al., 2009). Therefore, selection of individual SNPs based on hypotheses alone may not capture considerable genotypic variation associated with different study populations.
Hierarchical Classes Analysis (HICLAS) is a method for representing set-theoretical patterns for two-way, two-mode binary matrices (De Boeck and Rosenberg, 1988). HICLAS was employed in this study to represent SNP (allele) covariation patterns, and on the basis of those patterns, reduced the number of SNPs analyzed in relation to specific phenotypes. HICLAS assumes that SNP allelic distributions are modeled in a binary array. That is, for any given biallelic SNP (e.g. rs3924999), patient genotypes were represented as 00, 10 (01), or 11. 00 denotes an individual’s genotype is homozygous for the first allele (e.g. TT), 10 (or 01) denotes the individual’s genotype is heterozygous (e.g. TC), and 11 denotes the genotype is homozygous for the second allele (e.g. CC). To model a patient with respect to 6 SNP genotypes (12 alleles) there would be 12 binary entries, such as ‘001111001010’. The representation of the genotype (allele) patterns in a sample of 90 patients is accomplished by concatenating the data from individual patients row-wise, yielding a 90×12 binary matrix.
However, with rare exceptions, multiple algebraic decompositions exist for a two-way binary matrix. Unlike Boolean factor analysis (also compatible with two-way binary matrices), the HICLAS model has compatible and incompatible decompositions. The devised algorithm guarantees that the decomposition is compatible to the set-theoretical formulation of the model (De Boeck and Rosenberg, 1988). The equivalence and order relations (superset-subset) among object classes (here patients) and attribute classes (here SNPs) are summarized, as well as their association to each other. A HICLAS model of a two-way binary array is compared to the actual data array using a Jaccard measure (goodness of fit of the model to the data), ranging from 0 to 1, where 1 indicates perfect fit. Previous simulations have shown that HICLAS is able to recover the a priori categorical structure of the data matrix when random error is added (De Boeck and Rosenberg, 1988). Thus, HICLAS can identify patterns among row (patients) and column (allele) bundles, making it an optimal SNP/allele data reduction strategy for subsequent analyses in relation to various phenotypes.
In addition to significant genetic heterogeneity (Hallmayer et al., 2005; Sebat et al., 2009), schizophrenia has considerable phenotypic heterogeneity as specific perceptual, cognitive and behavioral abnormalities are only observed in patient subpopulations (Carpenter and Buchanan, 1994; Heinrichs, 2001; Raffard and Bayard, 2012). While the assessment of many perceptual and cognitive domains in schizophrenia is susceptible to generalized deficit confounds (Carter, 2005; Chapman and Chapman, 1978; Knight and Silverstein, 2001; MacDonald and Carter, 2002; Silverstein, 2008), several specific visual processes have been assessed in a manner that avoids many confounds (Dakin et al., 2005; Dima et al., 2009; Keane et al., 2013a, 2013b). One example is visual perceptual organization (Silverstein and Keane, 2011; Silverstein et al., 2013; Uhlhaas and Silverstein, 2005).

Results br Discussion The demand


The demand for knowledge on evidence-based interventions on the working environment is growing, yet, our example from the construction industry shows that in spite of an extensive search for literature, the desired information is not always available. Our review of the literature revealed that the scientific evidence on MSB interventions was limited for the specific target group of very small (micro) enterprises in the construction industry. The challenge was to find a way to use the available evidence in order to tailor the prevention packages to small enterprises in the construction industry. In order to do so, the realist analysis of mechanism and context suggested by Pawson and Tilley [11,12] has proven to be a useful tool to transfer the rather limited scientific evidence into circumstances where it has never been tested. Further, knowledge gaps had to be filled with the best judgement of researchers and practitioners in the field. At times, we had to move from \”known knowns to known unknowns\” as Pawson et al. [70] put it, and try to make the best judgement about qualified solutions. An example can be the use of lifting aids, which has been tested in very different contexts, such as manufacturing and health care but not in small construction enterprises.
Another problem is that there is little intervention research aimed at enterprises of this size. One important explanation is that it is difficult to design intervention studies which meet the methodological standard quality criteria. It is difficult and expensive to approach many small enterprises in order to reach a suitable URMC-099 size; they are reluctant to participate in time consuming interventions, and many small enterprises have a short life span [7]. Most intervention studies are therefore aimed at larger enterprises. This point is emphasised by the fact that the only systematic review of intervention studies aimed at small enterprises found only very few studies which fulfilled the quality criteria [10]. It is thus necessary to transfer knowledge from other fields to small enterprises in order to prepare qualified intervention programmes.
The important point of this paper is that the process of transferring knowledge from one field to another and making judgements about known-unknowns has to be done in a systematic way. It will make the design process transparent and thereby make it possible to criticise the design and subsequently to learn from the results of the completed intervention. We have therefore developed a model for such a systematic design process. The model builds on a realist analysis and this is used to build the programme theory for mechanisms which should make the programme work. However, one of the major constraints for the transfer of knowledge from one field to another is that numerous intervention researches do not include proper information about the concrete implementation procedure as well as the context of the intervention [71,72]. It is therefore difficult to judge how a specific intervention could be transferred to another context when little is known about how it was implemented in the first place.
In scientific intervention studies, new approaches can be tested. Yet, at the societal level, intervention programmes aimed at a general application need to be built on the best available evidence. However, the concrete evidence will always be fragmented. There will be holes of known-unknowns which have to be filled in one way or another in order to develop a workable programme. Our suggestion is to use a systematic model to develop the programme theory for the intervention programme. By making a systematic analysis of the context and make explicit judgements about the transfer of knowledge, it is possible to outline a transparent programme theory which can be the subject for critical assessment by researchers and practitioners. The principle for the assessment will be the guidelines suggested by Pawson and Tilley [12] on evaluating when the programme works, for whom it works, and under what circumstances it works. Such an assessment can then be used to improve the elements in the programme, or alternatively, to abandon the programme if it turns out that the programme theory is not working as expected.