Product innovation in a medium size mature manufacturing company

This thesis is concerned with the management of product innovation inside the medium size, mature, manufacturing company. An academic perspective of innovation is integrated with an account of direct participation acquired over a two year period. The emergent synthesis provides fresh insight into some of the problems associated with producing and sustaining innovation. Product innovation is a very complex activity, and it presents particular difficulties for mature industry. However, the ability to innovate is fundamental to a company's continued survival. Three aspects of product innovation are examined in detail. Firstly, is the requirement to separate innovation activity from the on-going business interests; dependency between the degree of separation and novelty is supported. Secondly, a simple sequential model of the innovation process is tested and shown to be of considerable practical value. Thirdly a relationship is established between the age of the recipient market and the type of innovation to be found in that market All three aspects are found to have important implications for management in their pursuit of innovation. Management deficiencies which inhibited the successful resolution of innovation-linked problems are described and solutions which stress the need for commitment and coherency are proposed. The long existing management structure in the mature company which mitigates against successful and continuing innovation are examined in detail and a strategy is evolved which uses the intrinsic strengths of the mature company to promote innovation of a kind compatible with success in the market. A set of guidelines of practical value is presented for those managers wishing to pursue, and sustain, product innovation in the medium size mature company

The effect of underwater massage during hot water immersion on acute cardiovascular and mood responses

Purpose: There is emerging evidence that demonstrates the health benefits of hot water immersion including improvements to cardiovascular health and reductions in stress and anxiety. Many commercially available hot tubs offer underwater massage systems which purport to enhance many benefits of hot water immersion, however, these claims have yet to be studied. Methods: Twenty participants (4 females) completed three, 30-minute sessions of hot-water immersion (beginning at 39°C) in a crossover randomized design: with air massage (Air Jet), water massage (Hydro Jet) or no massage (Control). Cardiovascular responses comprising; heart rate, blood pressure and superficial femoral artery blood flow and shear rate were measured. State trait anxiety, basic affect, and salivary cortisol were recorded before and after each trial. Data were analysed using a mixed effects model.Results: Post immersion, heart rate increased (Δ31bpm, P &lt; 0.001, d = 1.38), mean arterial blood pressure decreased (Δ16 mmHg, P&lt;0.001, d = −0.66), with no difference between conditions. Blood flow and mean shear rate increased following immersion (P &lt; 0.001, Δ362 ml/min, d = 1.20 and Δ108 s−1, d = 1.00), but these increases were blunted in the Air Jet condition (P &lt; 0.001,Δ171 ml/min, d = 0.43 and Δ52 s−1, d = 0.52). Anxiety and salivary cortisol were reduced (P = 0.003, d = −0.20, P = 0.014, d = −0.11), but did not vary between conditions. Enjoyment did not vary between conditions.Conclusion: These data demonstrate positive acute responses to hot water immersion on markers of cardiovascular function, anxiety, and stress. There was no additional benefit of water-based massage, while air-basedmassage blunted some positive vascular responses due to lower heat conservation of the water. <br/

Post exercise hot water immersion and hot water immersion in isolation enhance vascular, blood marker, and perceptual responses when compared to exercise alone

Exercise and passive heating induce some similar vascular hemodynamic, circulating blood marker, and perceptual responses. However, it remains unknown whether post exercise hot water immersion can synergise exercise derived responses and if they differ from hot water immersion alone. This study investigated the acute responses to post moderate-intensity exercise hot water immersion (EX+HWI) when compared to exercise (EX+REST) and hot water immersion (HWI+HWI) alone. Sixteen physically inactive middle-aged adults (nine males and seven females) completed a randomized cross-over counterbalanced design. Each condition consisted of two 30-min bouts separated by 10 min of rest. Cycling was set at a power output equivalent to 50% V̇o2 peak. Water temperature was controlled at 40°C up to the mid sternum with arms not submerged. Venous blood samples and artery ultrasound scans were assessed at 0 (baseline), 30 (immediately post stressor one), 70 (immediately post stressor two), and 100 min (recovery). Additional physiological and perceptual measures were assessed at 10-min intervals. Brachial and superficial femoral artery shear rates were higher after EX+HWI and HWI+HWI when compared with EX+REST (p &lt; 0.001). Plasma nitrite was higher immediately following EX+HWI and HWI+HWI than EX+REST (p &lt; 0.01). Serum interleukin-6 was higher immediately after EX+HWI compared to EX+REST (p = 0.046). Serum cortisol was lower at 30 min in the HWI+HWI condition in contrast to EX+REST (p = 0.026). EX+HWI and HWI+HWI were more enjoyable than EX+REST (p &lt; 0.05). Irrespective of whether hot water immersion proceeded exercise or heating, hot water immersion enhanced vascular and blood marker responses, while also being more enjoyable than exercise alone

The health benefits of passive heating and aerobic exercise: to what extent do the mechanisms overlap?

Exercise can induce numerous health benefits that can reduce the risk of chronic diseases and all-cause mortality, yet a significant percentage of the population do not meet minimal physical activity guidelines. Several recent studies have shown that passive heating can induce numerous health benefits, many of which are comparable to exercise, such as improvements to cardiorespiratory fitness, vascular health, glycaemic control and chronic low-grade inflammation. As such, passive heating is emerging as a promising therapy for populations who cannot perform sustained exercise or display poor exercise adherence. There appears to be some overlap between the cellular signalling responses that are regulated by temperature and the mechanisms that underpin beneficial adaptations to exercise, but detailed comparisons have not yet been made. Therefore, the purpose of this mini review is to assess the similarities and distinctions between adaptations to passive heating and exercise. Understanding the potential shared mechanisms of action between passive heating and exercise may help to direct future studies to implement passive heating more effectively and identify differences between passive heating and exercise induced adaptations

Rapid Diagnosis of Tuberculosis with the Xpert MTB/RIF Assay in High Burden Countries: A Cost-Effectiveness Analysis

A cost-effectiveness study by Frank Cobelens and colleagues reveals that Xpert MTB/RIF is a cost-effective method of tuberculosis diagnosis that is suitable for use in low- and middle-income settings

Viral Bcl2s' transmembrane domain interact with host Bcl2 proteins to control cellular apoptosis

Viral control of programmed cell death relies in part on the expression of viral analogs of the B-cell lymphoma 2 (Bcl2) protein known as viral Bcl2s (vBcl2s). vBcl2s control apoptosis by interacting with host pro- and anti-apoptotic members of the Bcl2 family. Here, we show that the carboxyl-terminal hydrophobic region of herpesviral and poxviral vBcl2s can operate as transmembrane domains (TMDs) and participate in their homo-oligomerization. Additionally, we show that the viral TMDs mediate interactions with cellular pro- and anti-apoptotic Bcl2 TMDs within the membrane. Furthermore, these intra-membrane interactions among viral and cellular proteins are necessary to control cell death upon an apoptotic stimulus. Therefore, their inhibition represents a new potential therapy against viral infections, which are characterized by short- and long-term deregulation of programmed cell death

Sequencing of prostate cancers identifies new cancer genes, routes of progression and drug targets

Prostate cancer represents a substantial clinical challenge because it is difficult to predict outcome and advanced disease is often fatal. We sequenced the whole genomes of 112 primary and metastatic prostate cancer samples. From joint analysis of these cancers with those from previous studies (930 cancers in total), we found evidence for 22 previously unidentified putative driver genes harboring coding mutations, as well as evidence for NEAT1 and FOXA1 acting as drivers through noncoding mutations. Through the temporal dissection of aberrations, we identified driver mutations specifically associated with steps in the progression of prostate cancer, establishing, for example, loss of CHD1 and BRCA2 as early events in cancer development of ETS fusion-negative cancers. Computational chemogenomic (canSAR) analysis of prostate cancer mutations identified 11 targets of approved drugs, 7 targets of investigational drugs, and 62 targets of compounds that may be active and should be considered candidates for future clinical trials

Analysis of the genetic phylogeny of multifocal prostate cancer identifies multiple independent clonal expansions in neoplastic and morphologically normal prostate tissue.

Genome-wide DNA sequencing was used to decrypt the phylogeny of multiple samples from distinct areas of cancer and morphologically normal tissue taken from the prostates of three men. Mutations were present at high levels in morphologically normal tissue distant from the cancer, reflecting clonal expansions, and the underlying mutational processes at work in morphologically normal tissue were also at work in cancer. Our observations demonstrate the existence of ongoing abnormal mutational processes, consistent with field effects, underlying carcinogenesis. This mechanism gives rise to extensive branching evolution and cancer clone mixing, as exemplified by the coexistence of multiple cancer lineages harboring distinct ERG fusions within a single cancer nodule. Subsets of mutations were shared either by morphologically normal and malignant tissues or between different ERG lineages, indicating earlier or separate clonal cell expansions. Our observations inform on the origin of multifocal disease and have implications for prostate cancer therapy in individual cases

Early infant HIV-1 diagnosis programs in resource-limited settings: opportunities for improved outcomes and more cost-effective interventions

Early infant diagnosis (EID) of HIV-1 infection confers substantial benefits to HIV-infected and HIV-uninfected infants, to their families, and to programs providing prevention of mother-to-child transmission (PMTCT) services, but has been challenging to implement in resource-limited settings. In order to correctly inform parents/caregivers of infant infection status and link HIV-infected infants to care and treatment, a 'cascade' of events must successfully occur. A frequently cited barrier to expansion of EID programs is the cost of the required laboratory assays. However, substantial implementation barriers, as well as personnel and infrastructure requirements, exist at each step in the cascade. In this update, we review challenges to uptake at each step in the EID cascade, highlighting that even with the highest reported levels of uptake, nearly half of HIV-infected infants may not complete the cascade successfully. We next synthesize the available literature about the costs and cost effectiveness of EID programs; identify areas for future research; and place these findings within the context of the benefits and challenges to EID implementation in resource-limited settings