Can Aging in Place Be Cost Effective? A Systematic Review

Purpose of the Study

To systematically review cost, cost-minimization and cost-effectiveness studies for assisted living technologies (ALTs) that specifically enable older people to ‘age in place’ and highlight what further research is needed to inform decisions regarding aging in place.

Design

People aged 65+ and their live-in carers (where applicable), using an ALT to age in place at home opposed to a community-dwelling arrangement.

Methods

Studies were identified using a predefined search strategy on two key economic and cost evaluation databases NHS EED, HEED. Studies were assessed using methods recommended by the Campbell and Cochrane Economic Methods Group and presented in a narrative synthesis style.

Results

Eight eligible studies were identified from North America spread over a diverse geographical range. The majority of studies reported the ALT intervention group as having lower resource use costs than the control group; though the low methodological quality and heterogeneity of the individual costs and outcomes reported across studies must be considered.

Implications

The studies suggest that in some cases ALTs may reduce costs, though little data were identified and what there were was of poor quality. Methods to capture quality of life gains were not used, therefore potential effects on health and wellbeing may be missed. Further research is required using newer developments such as the capabilities approach. High quality studies assessing the cost-effectiveness of ALTs for ageing in place are required before robust conclusion on their use can be drawn.     

When Can Antibiotic Treatments for Trachoma Be Discontinued? Graduating Communities in Three African Countries

Background

Repeated mass azithromycin distributions are effective in controlling the ocular strains of chlamydia that cause trachoma. However, it is unclear when treatments can be discontinued. Investigators have proposed graduating communities when the prevalence of infection identified in children decreases below a threshold. While this can be tested empirically, results will not be available for years. Here we use a mathematical model to predict results with different graduation strategies in three African countries.

Methods

A stochastic model of trachoma transmission was constructed, using the parameters with the maximum likelihood of obtaining results observed from studies in Tanzania (with 16% infection in children pre-treatment), The Gambia (9%), and Ethiopia (64%). The expected prevalence of infection at 3 years was obtained, given different thresholds for graduation and varying the characteristics of the diagnostic test.

Results

The model projects that three annual treatments at 80% coverage would reduce the mean prevalence of infection to 0.03% in Tanzanian, 2.4% in Gambian, and 12.9% in the Ethiopian communities. If communities graduate when the prevalence of infection falls below 5%, then the mean prevalence at 3 years with the new strategy would be 0.3%, 3.9%, and 14.4%, respectively. Graduations reduced antibiotic usage by 63% in Tanzania, 56% in The Gambia, and 11% in Ethiopia.

Conclusion

Models suggest that graduating communities from a program when the infection is reduced to 5% is a reasonable strategy and could reduce the amount of antibiotic distributed in some areas by more than 2-fold.     

Activation of Plant Nod-like Receptors: How Indirect Can It Be?

Pioneering plant research has shown that many Nod-like receptors (NLRs) detect pathogens indirectly via recognizing modifications of other host proteins. In this issue, two groups show that the RPM1 NLR is activated by phosphorylation of the host protein RIN4, probably resulting from activation of a host kinase by pathogen effectors.     

Can CD44 Be a Mediator of Cell Destruction? The Challenge of Type 1 Diabetes

CD44 is a multi-functional receptor with multiple of isoforms engaged in modulation of cell trafficking and transmission of apoptotic signals. We have previously shown that injection of anti-CD44 antibody into NOD mice induced resistance to type 1 diabetes (T1D). In this communication we describe our efforts to understand the mechanism underlying this effect. We found that CD44-deficient NOD mice develop stronger resistance to T1D than wild-type littermates. This effect is not explained by the involvement of CD44 in cell migration, because CD44-deficient inflammatory cells surprisingly had greater invasive potential than the corresponding wild type cells, probably owing to molecular redundancy. We have previously reported and we show here again that CD44 expression and hyaluronic acid (HA, the principal ligand for CD44) accumulation are detected in pancreatic islets of diabetic NOD mice, but not of non-diabetic DBA/1 mice. Expression of CD44 on insulin-secreting β cells renders them susceptible to the autoimmune attack, and is associated with a diminution in β-cells function (e.g., less insulin production and/or insulin secretion) and possibly also with an enhanced apoptosis rate. The diabetes-supportive effect of CD44 expression on β cells was assessed by the TUNEL assay and further strengthened by functional assays exhibiting increased nitric oxide release, reduced insulin secretion after glucose stimulation and decreased insulin content in β cells. All these parameters could not be detected in CD44-deficient islets. We further suggest that HA-binding to CD44-expressing β cells is implicated in β-cell demise. Altogether, these data agree with the concept that CD44 is a receptor capable of modulating cell fate. This finding is important for other pathologies (e.g., cancer, neurodegenerative diseases) in which CD44 and HA appear to be implicated.     

The Global Burden of Childhood Coeliac Disease: A Neglected Component of Diarrhoeal Mortality?

Objectives

Coeliac disease has emerged as an increasingly recognised public health problem over the last half-century, and is now coming to be seen as a global phenomenon, despite a profound lack of globally representative epidemiological data. Since children with coeliac disease commonly present with chronic diarrhoea and malnutrition, diagnosis is often overlooked, particularly in poorer settings where children often fail to thrive and water-borne infectious diarrhoeas are common. This is the first attempt to make global estimates of the burden of coeliac disease in childhood.

Methods

We built a relatively crude model of childhood coeliac disease, incorporating estimates of population prevalence, probability of non-diagnosis, and likelihood of mortality among the undiagnosed across all countries from 1970 to 2010, based around the few available data. All our assumptions are stated in the paper and the model is available as a supplementary file.

Findings

Our model suggests that in 2010 there were around 2.2 million children under 5 years of age living with coeliac disease. Among these children there could be 42,000 deaths related to coeliac disease annually. In 2008, deaths related to coeliac disease probably accounted for approximately 4% of all childhood diarrhoeal mortality.

Conclusions

Although coeliac disease may only account for a small proportion of diarrhoeal mortality, these deaths are not preventable by applying normal diarrhoea treatment guidelines, which may even involve gluten-based food supplements. As other causes of diarrhoeal mortality decline, coeliac disease will become a proportionately increasing problem unless consideration is given to trying gluten-free diets for children with chronic diarrhoea and malnutrition.     

Can Bibliographic Pointers for Known Biological Data Be Found Automatically? Protein Interactions as a Case Study

The Dictionary of Interacting Proteins (DIP) (Xenarios et al., 2000) is a large repository of protein interactions: its March 2000 release included 2379 protein pairs whose interactions have been detected by experimental methods. Even if many of these correspond to poorly characterized proteins, the result of massive yeast two-hybrid screenings, as many as 851 correspond to interactions detected using direct biochemical methods.We used information retrieval technology to search automatically for sentences in Medline abstracts that support these 851 DIP interactions. Surprisingly, we found correspondence between DIP protein pairs and Medline sentences describing their interactions in only 30% of the cases. This low coverage has interesting consequences regarding the quality of annotations (references) introduced in the database and the limitations of the application of information extraction (IE) technology to Molecular Biology. It is clear that the limitation of analyzing abstracts rather than full papers and the lack of standard protein names are difficulties of considerably more importance than the limitations of the IE methodology employed. A positive finding is the capacity of the IE system to identify new relations between proteins, even in a set of proteins previously characterized by human experts. These identifications are made with a considerable degree of precision.THIS IS, TO OUR KNOWLEDGE, THE FIRST LARGE SCALE ASSESSMENT OF IE CAPACITY TO DETECT PREVIOUSLY KNOWN INTERACTIONS: we thus propose the use of the DIP data set as a biological reference to benchmark IE systems.     

The Benefits of Photorespiratory Bypasses: How Can They Work?

Bypassing the photorespiratory pathway is regarded as a way to increase carbon assimilation and, correspondingly, biomass production in C₃ crops. Here, the benefits of three published photorespiratory bypass strategies are systemically explored using a systems-modeling approach. Our analysis shows that full decarboxylation of glycolate during photorespiration would decrease photosynthesis, because a large amount of the released CO₂ escapes back to the atmosphere. Furthermore, we show that photosynthesis can be enhanced by lowering the energy demands of photorespiration and by relocating photorespiratory CO₂ release into the chloroplasts. The conductance of the chloroplast membranes to CO₂ is a key feature determining the benefit of the relocation of photorespiratory CO₂ release. Although our results indicate that the benefit of photorespiratory bypasses can be improved by increasing sedoheptulose bisphosphatase activity and/or increasing the flux through the bypass, the effectiveness of such approaches depends on the complex regulation between photorespiration and other metabolic pathways.In C₃ plants, the first step of photosynthesis is the fixation of CO₂ by ribulose bisphosphate (RuBP). For every molecule of CO₂ fixed, this reaction produces two molecules of a three-carbon acid, i.e., 3-phosphoglycerate (PGA), and is catalyzed by the Rubisco enzyme. A small portion of the carbon in PGA is used for the production of Suc and starch, whereas the remainder (i.e. five-sixths) is used for the regeneration of RuBP (Fig. 1). The regeneration of the Rubisco substrate RuBP in the Calvin-Benson-Bassham (CBB) cycle ensures that ample RuBP is available for carbon fixation (Bassham, 1964; Wood, 1966; Beck and Hopf, 1982). Rubisco is a bifunctional enzyme that catalyzes not only RuBP carboxylation but also RuBP oxygenation (Spreitzer and Salvucci, 2002). RuBP oxygenation generates only one molecule of PGA and one molecule of 2-phosphoglycolate (P-Gly; Ogren, 1984). The photorespiratory pathway converts this P-Gly back to RuBP in order to maintain the CBB cycle.Open in a separate windowFigure 1.Schematic representation of the C3 photosynthesis kinetic model with three different photorespiratory bypass pathways. The bypass described by Kebeish et al. (2007) is indicated in blue, the bypass described by Maier et al. (2012) in pink, and the bypass described by Carvalho et al. (2011) in green. The original photorespiratory pathway is marked in orange, and CO₂ released from photorespiration (including the original pathway and bypass pathways) is indicated in red. 2PGA, 2-Phosphoglyceric acid; ASP, Asp; CIT, citrate; ICIT, isocitrate; PGA, 3-phosphoglycerate; DPGA, glycerate-1,3-bisphosphate; GAP, glyceraldehyde 3-phosphate; DHAP, dihydroxyacetone phosphate; SBP, sedoheptulose-1,7-bisphosphate; S7P, sedoheptulose-7-phosphate; Ri5P, ribose-5-phosphate; Ru5P, ribulose-5-phosphate; FBP, fructose-1,6-bisphosphatase; F6P, fructose 6-phosphate; Xu5P, xylulose-5-phosphate; G6P, glucose-6-phosphate; G1P, glucose-1-phosphate; ADPG, ADP-glucose; F26BP, fructose-2,6-bisphosphate; UDPG, uridine diphosphate glucose; SUCP, sucrose-6F-phosphate; SUC, Suc; PEP, phosphoenolpyruvate; OAA, oxaloacetate; PGCA, phosphoglycolate; GCA, glycolate; GOA, glyoxylate; GCEA, glycerate; MAL, malate; PYR, pyruvate; GLU, glutamate; KG, alfa-ketoglutarate; GLN, Gln; HPR, hydroxypyruvate; RuBP, ribulose bisphosphate; SER, Ser; GLY, Gly; TS, tartronic semialdehyde.In higher plants, P-Gly is dephosphorylated to glycolate, which is transferred into the peroxisomes, where it is oxidized to hydrogen peroxide and glyoxylate. Then, glyoxylate is aminated to produce Gly, which is subsequently transferred to the mitochondria. There, two molecules of Gly are converted into one Ser plus one CO₂ and one NH₃ (Ogren, 1984; Peterhansel et al., 2010). The Ser is ultimately converted back to PGA (Tolbert, 1997). CO₂ and NH₃ are gasses that can escape to the atmosphere (Sharkey, 1988; Kumagai et al., 2011), and the loss of carbon and nitrogen essential for biomass accumulation will decrease the efficiency of photosynthesis and plant growth (Zhu et al., 2010). Fortunately, both substances are partially reassimilated in the chloroplast, but this results in decreased photosynthetic energy efficiency. At 25°C and current atmospheric CO₂ concentrations, approximately 30% of the carbon fixed in C₃ photosynthesis may be lost via photorespiration and the size of this loss increases with temperature (Sharkey, 1988; Zhu et al., 2010). As a result, photorespiration has been regarded as a pathway that could be altered to improve photosynthetic efficiency (Zelitch and Day, 1973; Oliver, 1978; Ogren, 1984; Zhu et al., 2008, 2010).There are several approaches that may be used to alter photorespiration to improve photosynthetic efficiency. First, it might be possible to increase the specificity of Rubisco to CO₂ versus oxygen (S_c/o; Dhingra et al., 2004; Spreitzer et al., 2005; Whitney and Sharwood, 2007). However, previous studies have shown that there is an inverse correlation between S_c/o and the maximum carboxylation rate of Rubisco (Jordan and Ogren, 1983; Zhu et al., 2004), and there are some indications that the S_c/o of different organisms may be close to optimal for their respective environments (Tcherkez et al., 2006; Savir et al., 2010). Second, a CO₂-concentrating mechanism could be engineered into C₃ plants. For example, introducing cyanobacterial bicarbonate transporters (Price et al., 2011) or introducing C₄ metabolism could be used to concentrate CO₂ in the vicinity of Rubisco and, thereby, suppress the oxygenation reaction of Rubisco (Furbank and Hatch, 1987; Mitchell and Sheehy, 2006). Past efforts to introduce a C₄ pathway into C₃ plants have focused on biochemical reactions related to C₄ photosynthesis without taking into account the anatomical differences between C₃ and C₄ plants, which may have been responsible for the limited success of such endeavors (Fukayama et al., 2003). Recently, there has been renewed interest in engineering C₄ photosynthetic pathways into C₃ plants, with efforts focusing on understanding and engineering the genetic regulatory network related to the control of both the anatomical and biochemical properties related to C₄ photosynthesis (Mitchell and Sheehy, 2006; Langdale, 2011).Transgenic approaches have been used to knock down or knock out enzymes in the photorespiratory pathway. Unfortunately, the inhibition of photorespiration by the deletion or down-regulation of enzymes in the photorespiratory pathway resulted in a conditional lethal phenotype (i.e. such plants cannot survive under ambient oxygen and CO₂ concentrations but may be rescued by growing them under low-oxygen or high-CO₂ conditions; for review, see Somerville and Ogren, 1982; Somerville, 2001). Another approach to reduce photorespiration is to block (or inhibit) enzymes in this pathway using chemical inhibitors. Zelitch (1966, 1974, 1979) reported that net photosynthesis increased by inhibiting glycolate oxidase or glycolate synthesis. However, other groups showed that the inhibition of glycolate oxidase or Gly decarboxylation led to the inhibition of photosynthesis (Chollet, 1976; Kumarasinghe et al., 1977; Servaites and Ogren, 1977; Baumann et al., 1981). It turns out that plants cannot efficiently metabolize photorespiratory intermediates without a photorespiratory pathway, and suppression of this pathway inhibits the recycling of carbon back toward RuBP, which is necessary for maintaining the CBB cycle (Peterhansel et al., 2010; Peterhansel and Maurino, 2011). Moreover, the accumulation of toxic metabolic intermediates (e.g. P-Gly) can strongly inhibit photosynthesis (Anderson, 1971; Kelly and Latzko, 1976; Chastain and Ogren, 1989; Campbell and Ogren, 1990). This may explain why earlier attempts to block or reduce photorespiration have failed to improve carbon gain.Instead of reducing photorespiration directly, a promising idea is to engineer a photorespiratory bypass pathway. Such a pathway would metabolize P-Gly produced by RuBP oxygenation but minimize carbon, nitrogen, and energy losses and avoid the accumulation of photorespiratory intermediates. Kebeish et al. (2007) introduced the glycolate catabolic pathway from Escherichia coli into Arabidopsis (Arabidopsis thaliana); we will subsequently call this type of bypass the Kebeish bypass. In such transgenic plants, glycolate is converted to glycerate in the chloroplasts without ammonia release (Fig. 1). Previous studies suggested that this pathway theoretically requires less energy and shifts CO₂ release from mitochondria to chloroplasts (Peterhansel and Maurino, 2011; Peterhansel et al., 2013); experimental results indicated that the bypass allowed for increased net photosynthesis and biomass production in Arabidopsis (Kebeish et al., 2007). There are reports of two other photorespiratory bypass pathways in the literature (Carvalho, 2005; Carvalho et al., 2011; Maier et al., 2012). In the Carvalho bypass (Carvalho, 2005; Carvalho et al., 2011), glyoxylate is converted to hydroxypyruvate in the peroxisome. Similar to the Kebeish bypass, the ammonia release is abolished, one-quarter of the carbon from glycolate is released as CO₂ in the peroxisomes, and three-quarters of the carbon from glycolate is converted back to PGA. However, this pathway has only been partially realized in tobacco (Nicotiana tabacum); that is, the enzyme of the second reaction of this pathway was not detectable in the transgenic plants, and plants expressing this pathway showed stunted growth when grown in ambient air (Carvalho et al., 2011). The Maier bypass (Maier et al., 2012) is characterized by complete oxidation of glycolate in the chloroplasts. Initial results suggested that the photosynthesis and biomass of transgenic Arabidopsis with this pathway were enhanced (Maier et al., 2012).Recently, the design and benefits of the three bypass pathways were reviewed (Peterhansel et al., 2013), and it was suggested that a photorespiratory bypass can contribute to an enhanced photosynthetic CO₂ uptake rate by lowering energy costs and minimizing carbon and nitrogen losses. However, a systematic and quantitative analysis of the potential contributions of these different factors to photosynthesis improvement has not yet been conducted. Systems modeling can help to design new metabolic pathways and improve our understanding of biochemical mechanisms (McNeil et al., 2000; Wendisch, 2005; Zhu et al., 2007; Bar-Even et al., 2010; Basler et al., 2012). Such models have been used successfully to gain insight into the photosynthetic metabolism (Laisk et al., 1989, 2006; Laisk and Edwards, 2000; Zhu et al., 2007, 2013; Wang et al., 2014). In this study, we use an extended kinetic model of C₃ photosynthesis based on earlier work by Zhu et al. (2007) to systematically analyze the potential of three photorespiratory bypass pathways for improving photosynthetic efficiency (Supplemental Model S1). In addition, we determined under what conditions such bypass pathways may lead to increased photosynthesis and biomass production in C₃ plants and how to further improve the photosynthesis of plants with such a bypass. Our analysis suggests that the benefit of a photorespiratory bypass varies dramatically if it is engineered into different crops.     

The Global Burden of Disease Assessments—WHO Is Responsible?

The Global Burden of Disease (GBD) concept has been used by the World Health Organization (WHO) for its reporting on health information for nearly 10 years. The GBD approach results in a single summary measure of morbidity, disability, and mortality, the so-called disability-adjusted life year (DALY). To ensure transparency and objectivity in the derivation of health information, WHO has been urged to use reference groups of external experts to estimate burden of disease. Under the leadership and coordination of WHO, expert groups have been appraising and abstracting burden of disease information. Examples include the Child Health Epidemiology Reference Group (CHERG), the Malaria Monitoring and Evaluation Reference Group (MERG), and the recently established Foodborne Disease Burden Epidemiology Reference Group (FERG). The structure and functioning of and lessons learnt by these groups are described in this paper. External WHO expert groups have provided independent scientific health information while operating under considerable differences in structure and functioning. Although it is not appropriate to devise a single "best practice" model, the common thread described by all groups is the necessity of WHO's leadership and coordination to ensure the provision and dissemination of health information that is to be globally accepted and valued.     

Limbs vs. Jaws: Can They Be Compared?

Current experimental research on mammalian limb muscle structureand function is compared to that on mammalian jaw muscles. Twomajor areas of comparison are stressed: structural and functional.Comparisons of limbs and jaws are made from the point of viewof the impact of recent studies on simple mechanical modelsof limb/jaw muscle function. Limb muscle structure is comparedto jaw muscles at the level of muscle architecture, muscle histochemicaland motor unit properties, and the organization of motor unitsinto neuromuscular compartments. Such comparisons reveal thatalthough limb muscles and jaw muscles might be organized insimilar ways, fundamental differences exist, both in terms ofmuscle structure and the functional conclusions which have beenbased on studies of muscle structure. The comparisons also demonstratethat much recent evidence from structural studies have had littledirect impact on simple models of muscle function but a muchlarger influence on the assumptions of the models. Comparisonsof limb/jaw muscle function from kinematic and EMG studies,indicate that many masticatory strategies are used by differentmammals but the basic problems of posture and locomotion havebeen met with essentially similar solutions, even among diversemammalian groups. The results of such comparisons demonstratethat both limb and jaw muscle function are sufficiently complexthat new or re-vitalized models are needed if the relationshipbetween structure and function are ever to be understood.     

Closing Yield Gaps: How Sustainable Can We Be?

Global food production needs to be increased by 60–110% between 2005 and 2050 to meet growing food and feed demand. Intensification and/or expansion of agriculture are the two main options available to meet the growing crop demands. Land conversion to expand cultivated land increases GHG emissions and impacts biodiversity and ecosystem services. Closing yield gaps to attain potential yields may be a viable option to increase the global crop production. Traditional methods of agricultural intensification often have negative externalities. Therefore, there is a need to explore location-specific methods of sustainable agricultural intensification. We identified regions where the achievement of potential crop calorie production on currently cultivated land will meet the present and future food demand based on scenario analyses considering population growth and changes in dietary habits. By closing yield gaps in the current irrigated and rain-fed cultivated land, about 24% and 80% more crop calories can respectively be produced compared to 2000. Most countries will reach food self-sufficiency or improve their current food self-sufficiency levels if potential crop production levels are achieved. As a novel approach, we defined specific input and agricultural management strategies required to achieve the potential production by overcoming biophysical and socioeconomic constraints causing yield gaps. The management strategies include: fertilizers, pesticides, advanced soil management, land improvement, management strategies coping with weather induced yield variability, and improving market accessibility. Finally, we estimated the required fertilizers (N, P₂O₅, and K₂O) to attain the potential yields. Globally, N-fertilizer application needs to increase by 45–73%, P₂O₅-fertilizer by 22–46%, and K₂O-fertilizer by 2–3 times compared to the year 2010 to attain potential crop production. The sustainability of such agricultural intensification largely depends on the way management strategies for closing yield gaps are chosen and implemented.     

The cultural nature of risk: Can there be an anthropology of uncertainty?

In risk research, culture has been used mainly as a 'black box' of unknowns into which 'irregularities' of risk perceptions that could not be otherwise accounted for can be referred. In social anthropology it has been taken for granted that what is to be considered a 'risk' depends entirely on cultural settings and assumptions; risks are culturally defined and selected. This article takes a critical stance towards any such simplistic ideas about risk and culture. Culture is approached from a perspective of cognitive theory and is hence understood as shared schemata that define categories, relationships and contexts, making it possible to process meanings and order information. It is argued that if we are to succeed in investigating risk contextually, without ending up in a relativistic muddle which merely acknowledges myriads of diverse risk perceptions, it is necessary to problematize the assumed simplistic cultural nature of risk.     

Gene Transfer: How Can the Biological Barriers Be Overcome?

Physical methods represent a promising approach for the safe delivery of therapeutic plasmid DNA in genetic and acquired human diseases. However, their development in clinics is limited by their low efficacy. At the cellular level, efficient gene transfer is dependent on several factors including extracellular matrix, plasmid DNA uptake and nucleocytoplasmic transport. We review the main barriers that plasmid DNA encounters from the extracellular environment toward the interior of the cell and the different strategies developed to overcome these biological barriers. Diffusional and metabolic fences of the extracellular matrix and the cytoplasm affect plasmid DNA uptake. These barriers reduce the number of intact plasmids that reach the nucleus. Nuclear uptake of plasmid DNA further requires either an increase of nuclear permeability or an active nuclear transport via the nuclear pore. A better understanding of the cellular and molecular bases of the physical gene-transfer process may provide strategies to overcome those obstacles that highly limit the efficiency and use of gene-delivery methods.     

Are Treatments More Effective than Placebos? A Systematic Review and Meta-Analysis

BackgroundPlacebos are widely used in clinical practice in spite of ethical restrictions. Whether such use is justified depends in part on the relative benefit of placebos compared to ‘active’ treatments. A direct test for differences between placebo and ‘active’ treatment effects has not been conducted.ObjectivesWe aimed to test for differences between treatment and placebo effects within similar trial populations.ResultsIn trials with continuous outcomes (n = 115) we found no difference between treatment and placebo effects (MD = −0.29, 95% CI −0.62 to 0.05, P = 0.10). In trials with binary outcomes (n = 37) treatments were significantly more effective than placebos (RRR = 0.72, 95%CI = 0.61 to 0.86, P = 0.0003). Treatment and placebo effects were not different in 22 out of 28 predefined subgroup analyses. Of the six subgroups with differences treatments were more effective than placebos in five. However when all criteria for reducing bias were ruled out (continuous outcomes) placebos were more effective than treatments (MD = 1.59, 95% CI = 0.40 to 2.77, P = 0.009).

Conclusions and Implications

Placebos and treatments often have similar effect sizes. Placebos with comparatively powerful effects can benefit patients either alone or as part of a therapeutic regime, and trials involving such placebos must be adequately blinded.     

Why Be Vigilant? The Case of the Alpha Animal

We compared patterns of vigilance behavior in a male- and a female-dominant species—white-faced capuchins and ring-tailed lemurs—and used the results to test four hypotheses to explain vigilance behavior in primates. Adult male white-faced capuchins spent significantly more time vigilant than females did, and much male vigilance appeared to be directed toward males from other social groups. This finding supports the protection of paternity hypothesis. No sex difference existed in vigilance behavior among the ring-tailed lemurs, and subjects of both sexes exhibited more vigilance toward predators/potential predators than toward extragroup conspecifics, which supports the predator detection hypothesis. A trade-off argument, suggesting that females tolerate males in a group in return for greater male vigilance, does not apply to ring-tailed lemurs in our study. In both the male-dominant capuchins and the female-dominant ring-tailed lemurs, the alpha subject in the majority of the study groups was significantly more vigilant than other group members were. In white-faced capuchins, the alpha male mates more often than subordinate males do; therefore, the greater degree of vigilance exhibited by the alpha male may correspond to the protection of his reproductive investment. In ring-tailed lemurs, there can be more than one matriline in a group. Thus, the greater amount of vigilance behavior exhibited by the alpha female may be related to protection of her matriline, which could ultimately lead to greater inclusive fitness. Alpha subjects in our study groups exhibited certain behaviors more frequently or exclusively. Accordingly, there may be a constellation of behaviors characteristic of alpha animals.     

Can Serum Testosterone Be Used as a Marker of Overall Health?

Low serum testosterone has been associated with obesity, type 2 diabetes, metabolic syndrome, and atherosclerosis. Individuals with these comorbidities are at increased risk of premature death and other adverse health effects. Clinical data portend low testosterone as a risk factor for developing these conditions which are supported by the hypogonadal-obesity-adipocytokine hypothesis. The authors support comprehensive evaluation for these comorbid conditions in men found to have low serum testosterone.Key words: Androgen deficiency, Aging male, Comorbidities, Diabetes, Cardiovascular diseaseTestosterone is a male sex hormone that affects sexual development and function and enhances muscle strength and bone density.¹ Low testosterone levels have been associated with a variety of comorbid conditions, such as metabolic syndrome (MetS), obesity, type 2 diabetes (T2D), and cardiovascular disease (CVD).^1–3 Each of these comorbid conditions is a strong risk factor that contributes to an increased risk of major adverse cardiovascular events.¹ In addition, low serum testosterone is inversely associated with increased mortality.^4,5This review explores the association between low serum testosterone and diseases that portend poor health, such as MetS, obesity, T2D, and CVD, and reviews current clinical studies and proposed mechanisms by which low testosterone is associated with these diseases.