It may not be as useful to patients with more severe TBI because they are largely amnesic of their trauma. As noted above, some severe TBI patients can have nightmares or intrusive memories on the basis of reconstructions of their trauma; in these cases, imaginable exposure to those mental representations that are causing anxiety. In most cases of moderate/severe TBI, however, it is more

useful to employ in vivo exposure because reminders of the trauma can elicit stronger anxiety in the absence of actual memories or images. A survivor of a motor vehicle accident who sustained a severe TBI may experience marked fear when watching film footage of traffic; in such a case, the patient could complete exposure by repeatedly watching Inhibitors,research,lifescience,medical traffic footage. Through these techniques it would be hoped that extinction learning can be achieved, even though the patient may never retrieve direct memories of the traumatic event. Conclusions The coexistence of TBI and PTSD is frequent, and the extent to which the symptoms of TBI and PTSD are confused may be as frequent. Increasing evidence Inhibitors,research,lifescience,medical indicates that many previously termed PCS responses are a function of psychological responses, and it hampers a patient’s recovery if they INCB024360 mistakenly perceive these

reactions as indicators of a brain Inhibitors,research,lifescience,medical injury that may be permanent. In this sense, the field is recognizing the distinction between TBI as an event rather than a syndrome, whereas PTSD Inhibitors,research,lifescience,medical or PCS are symptoms that arise secondary to the event. The likelihood that the presumed secpelae of MTBI are actually attributed to psychological responses to the traumatic experience is becoming more apparent. Accurate identification of the true nature and

cause of the symptoms experienced after TBI is important because if stress-related disturbances are mistakenly attributed to neurological factors, patients may be deprived Inhibitors,research,lifescience,medical of effective treatments that can, in most cases, alleviate the symptoms. As we learn more about the interaction of TBI and PTSD, it seems that we will be discovering much about how the brain responds to traumatic experiences, both in Adenylyl cyclase cases when there has and has not been a TBI. Understanding this interaction between neurological insult and psychological response has the potential to shed light on the key mechanisms underpinning trauma response generally, and how it is impacted by different levels of brain injury.
Psychological trauma can result from witnessing an event that is perceived to be life-threatening or to pose the potential of serious bodily injury to self or others. Such experiences, which are often accompanied by intense fear, horror, and helplessness, can lead to the development of, and are required for the diagnosis of, post-traumatic stress disorder (PTSD).1 It was originallythought that PTSD represented a normative response, at the extreme end of a response continuum, the severity of which related primarily to trauma/stressor intensity.

Materials and Methods Participants Nineteen right-handed (mean age 24.7, range 20–34 years; seven men) and eight left-handed (mean age 27.9, range 20–51 years; one man) healthy subjects participated in the study. All subjects received a magnetic resonance imaging (MRI) safety screening and gave written consent. They were moderately financially rewarded for

their participation in the study conducted in conformity with the declaration of Helsinki and approved by the local ethics committee. www.selleckchem.com/products/dabrafenib-gsk2118436.html design We manipulated moving Inhibitors,research,lifescience,medical finger (index finger of dominant hand, of nondominant hand, of both hands) and attention type (“attention-modulation free” as cued tapping with no further instruction, “distraction” as cued tapping while counting backward, and “concentration” as cued tapping while actively Inhibitors,research,lifescience,medical paying attention to the moving finger[s]). In the bimanual task, there was an additional condition “divided concentration” defined as paying attention to either the moving index finger of the dominant or nondominant hand. In sum, there were 11

Inhibitors,research,lifescience,medical conditions that were assessed in an functional (fMRI) block design (see Table 1). Table 1 Experimental tasks Each of the 11 experimental conditions was presented in four blocks

separated by blocks of rest (see Fig. 1). The sequence of the 11 experimental conditions Inhibitors,research,lifescience,medical was randomized. Handedness (see below) was used to assign dominant and nondominant hand as well as dominant and nondominant hemisphere for each subject. Movement frequency (main tapping frequency ascertained by fast Fourier transformation of the time series of button presses) and Inhibitors,research,lifescience,medical mean standard deviation of button presses in comparison to sound occurrence were determined as behavioral control variables. Figure 1 Experimental setup. Time course of the localizer scans, the 11 experimental conditions of the main experiment and the anatomical scan. Each experimental condition was repeated consecutively four times. Sequence of the 11 experimental conditions almost was assigned … Procedure and stimuli Participants received pretraining outside of the scanner consisting of a shortened version of the 11 tasks to make sure that they had understood the instructions. If they had any difficulties with any of the tasks, pretraining was repeated. Handedness was measured by the Edinburgh Handedness Inventory (Oldfield 1971).

Although the role of the DRD2 gene in antipsychotic response is not conclusive, these findings are of particular interest since D2 is the main target of antipsychotics.16 5-HT2A is proposed to be involved in the unique therapeutic action of clozapine.17 Two studies with sufficient statistical power have

demonstrated a role for the structural 5-FIT2A His452Tyr polymorphism in predicting clozapine response.18,19 Significant associations have also been described in at least a dozen other genes, such as DRD3, DRD4, 5-HT1A, 5-HT2C, 5-HT6, 5-HTT, BDNF, COMT, GNB3, MDR1, MTHFR, NEF3, NRG1, RGS4 and TNF-alpha. 2,20,21 Of note, the first whole genome-wide Inhibitors,research,lifescience,medical association study of antipsychotic drug response was recently conducted by Sullivan et al.21 This approach involves no a priori hypotheses of candidate Inhibitors,research,lifescience,medical genes or gene variants, and as a result makes it difficult to interpret the significance of results in the context of adequately controlling for multiple variable testing. No significant findings have been reported thus far. Also of note, only a few studies have selleck chemicals llc tested for a direct association between CYP450 gene polymorphisms and drug response. These have yielded mostly negative results.2,22 Inhibitors,research,lifescience,medical Overall, some interesting

findings exist in the area of genetics and antipsychotic response. However, many associations are not conclusive and represent a small fraction of the total variance of treatment outcome. Because the entire genome and candidate gene Inhibitors,research,lifescience,medical variability have not been fully explored, more robust observations are expected with the utilization of DNA sequencing techniques. The category

“treatment response” may be too broad an outcome measure in genetic studies of heterogeneous conditions. Studies that target specific symptoms, such as neurocognitive Inhibitors,research,lifescience,medical and verbal memory scores, may yield more convincing findings.21,23 Genetics of antipsychotic-induced side effects Antipsychotics can induce a variety of side effects, such as involuntary movements (eg, tardive dyskinesia) and weight gain, both of which appear to be genetically determined.24,25 Compared with phenotypes like treatment response, an analysis of genetic factors associated also with side effects may offer several advantages. First, side effects are often more closely related to plasma levels, which can sometimes be predicted by gene variants involved in drug metabolism. Second, compared with treatment response the occurrence of side effects maybe more closely related to specific pharmacodynamic relevant receptors. Third, some side effects such as weight gain can be assessed more easily and reliably as compared with complex phenotypes, such as treatment response. In a prototypical study of its time, Pollock et al26 prospectively distinguished poor P450 2D6 metabolizers from EM among a group of elderly patients suffering from dementia treated with perphenazine. The poor metabolizers had significantly greater side effects than the 40 extensive metabolizers.

But urinary schistosomiasis can have devastating impact on the urinary tract and indeed the whole kidney which, if not detected early and prompt interventions instituted, could be fatal.2,8 This, notwithstanding,

in most endemic countries, the extent of renal complications of schistosomiasis in children has not been fully established.2 It is believed to be higher than generally appreciated.9 The most prominent and important pathology in schistosomiasis results from the host response to schistosomal eggs retained in tissues.2,8,9 Following infection, the adult worms (male: female pairings) inhabit the venules of the urinary tract from where the females release Selleckchem Dabrafenib large quantities of eggs which may remain embedded in the tissues, embolise to other organs, or pass into the urine.8 Eggs trapped in selleck inhibitor tissues stimulate a strong granulomatous reaction which heals by fibrosis.2,8,9 On the urinary system, schistosomal nephropathy typically presents as granulomatous inflammation of the distal third of both ureters, the urinary bladder and the urethra and may be followed by calcification resulting in hydroureters, hydronephrosis, and bladder neck obstruction.2,,8,9 In the bladder, collections of fine mucosal tubercles called sandy

patches may develop as well as granulomas of various sizes (sessile or pedunculated).2 Persistent bladder schistosomiasis may be linked to squamous cell carcinoma of the bladder in adulthood.2,3 Besides its effect on the urinary tract,

schistosomal nephropathy may also present as immune-complex mediated glomerular disease typically as nephrotic syndrome.2,8–10 The chronic loss of blood that ensues from the persistent symptom of haematuria (overt or covert) may be a cause of iron deficiency anaemia and poor growth in children which may assume public health dimensions in heavily infected communities.2,11 The effect of urinary schistosomiasis is influenced by both the intensity of infection (judged by the eggs count) and the duration of infection.2,8,9 In this article, we present five of eight cases of urinary schistosomiasis that were seen in the paediatric nephrology/ urology units of Komfo Anokye Teaching Hospital (KATH) over a 2-year period. All five cases presented with obstructive uropathy, two of whom died from their disease; two underwent successful surgery; Vasopressin Receptor and one made a spontaneous “recovery”. The other three cases (not presented in this article) presented with acute glomerulonephritis-like syndrome and made complete recovery. Case 1 A 7-year old girl, EO, who had been admitted to the paediatric emergency unit of KATH with congestive heart failure (bibasal crepitations, cardiomegaly, tender hepatomegaly and peripheral oedema) and hypertension (BP 180/120mmHg) was subsequently found to have ova of Schistosoma haematobium in her urine. She had lived in Akosombo for greater part of her life.

Therapy itself would have to be matched to the patient by the ability to foresee a positive response and predict side effects (Figure 1). Finally, taking all the above into consideration, the algorithm will have to provide an answer to the patient: is the benefit worth the risk for me? Figure 1. Matching therapy to patients by foreseeing a positive response and predicting side effects. Little data is available to weigh treatment Inhibitors,research,lifescience,medical risks versus benefits. In a recent publication based on a single trial with a strictly defined patient population treatment success outweighed the risk of side effects.81 However, the specific patient population, the

specific drugs analyzed, and the short follow-up period only reiterate the difficulty in http://www.selleckchem.com/products/epacadostat-incb024360.html obtaining such solution for the variable

CD patient population. Another study demonstrated Inhibitors,research,lifescience,medical that patients place symptom control in high priority and are willing to tolerate the risks,82 which is an important consideration when treatment is formulated. CONCLUSION With the advancement of research, the wide array of new drugs which affect different disease mechanisms, and the increasing understanding of CD pathogenesis, the relevance of various Inhibitors,research,lifescience,medical biomarkers, and the natural course and response to treatment, it is mainly a question of time before highly efficacious, safe and personal treatment is Inhibitors,research,lifescience,medical available to CD patients. Abbreviations: ASCA anti-Saccharomyces cerevisiae; CD Crohn’s disease; CRP C-reactive protein; GM-CSF granulocyte macrophage colony-stimulating factor; IBD inflammatory bowel disease; LOR loss of response; OmpC outer membrane porin C; UC ulcerative colitis. Footnotes Conflict of interest: Dr. Chowers acted as an advisor for Abbott Laboratories and received lecture fees from them. He also served as an advisor for Schering Plough.
One of the goals of personalized medicine is to identify patients at risk for future Inhibitors,research,lifescience,medical cardiovascular events. Methods such as genomics, proteomics,

no metabolics, and transcriptomics are used to discern a marker or a set of markers that will identify the people who are at risk and also identify the optimal treatment for each individual. However, in certain areas, such as heart diseases, the predictability of these methods is lacking. About 1.4 million heart attacks (myocardial infarctions (MI)) occur in the United States every year. The most common screening for heart disease is done by taking a history and conducting minimally invasive blood tests at the doctor’s office. These tests provide certain parameters such as blood pressure, cholesterol glucose, and C-reactive protein levels, which, as shown in the Framingham study,1 are the traditional risk factors for development of heart disease.

Child passed away 72 hours into admission. Case 5 Twelve-year-old H. M. was referred to KATH from a district hospital with left flank pain and passage of scanty urine for 4 days. Epigenetic inhibitor She had been given IV fluids and IV frusemide at the district hospital on account of the oliguria yet urethral catheterisation yielded no urine. The flank pain had worsened subsequently with child wailing loudly that prompted urgent referral to KATH. Patient had lived in Krachie

near Akosombo for first 8 years of life where she experienced recurrent terminal haematuria for 4 yrs. Essential findings on physical examination were: BP 170/120mmHg; the rest of cardiovascular examination was normal. Chest was clinically clear. There was tenderness in the left lumbar region but the kidneys and bladder were not palpable. There was no peripheral oedema. Accompanying lab results showed Hb 9.7g/dl., MCV 75 fl, serum creatinine 1,947µmol/l, Na+ 128mmol/l, K+ 7.3mmol/l; urinalysis Fulvestrant nmr of protein 2+, blood 2+, pus cell 6–8/HPF, RBC >20/HPF, S. haematobium ova 2+; urine culture was negative. Salbutamol nebulisation 5mg hourly and sodium polysterene (kayexalate) per rectum were instituted to control the hyperkalaemia. IV hydralazine was started with oral amlodipine. Urethral catheter passed yielded no urine. Laboratory results

were: blood urea of 52.9 mmol/l, creatinine 2,282µmol/l, Na+ 127mmol/l and K+ 7.2mmol/l. USS showed severe bilateral hydroureteronephrosis with left peri-nephric collection. Bladder was empty with drainage

catheter in-situ. Diagnoses of acute kidney injury 2° schistosomal related obstructive uropathy, and worsening over hydronephrosis from IV fluids were made. Nephrostomy tubes were inserted into both kidneys. Urine output per nephrostomy tubes for the first 24 hours yielded 9.3mls/kg/hr. Fluid replacement in excess of 4ml/kg/hr of urine output was instituted. Patient also received full treatment with praziquantel. BP was controlled, and flank pain decreased substantially. Good recovery of kidney function was recorded three weeks after placement of the nephrostomy tubes with the following laboratory results: Three weeks into placement of nephrostomy tubes, new laboratory values of blood urea 5.8mmol/l, creatinine 93 µmol/l, Na+ 135mmol/l and 4.5 K+mmol/l were obtained. Anterograde pyelogram confirmed severe bilateral ureteral obstruction. Patient subsequently underwent bilateral ureteral reimplantation with placement of double J-stent. Intraoperative findings showed fibrotic bilateral distal ureters none of which was “passable” at the distal 2–3cm segment from the vesico-ureteric junction. Bladder wall was markedly thickened. Patient has done well postoperatively and is still being followed up. An interval IVU is planned to assess the success and patency of the distal ureters.

GWAS, genome-wide association studies; NHS, Nurses’ Health Study. Figure 3 Manhattan plot of the GWAS meta-analysis in four NHS substudies (N = 6989). GWAS, genome-wide association

studies; NHS, Nurses’ Health Study. NHS-GWAS-PS FRAX597 analyses The genome-wide PS similarly explained a small fraction of variance in the long-term average depression score (Table 3). Using the most liberal threshold of P < 0.5 to select SNPs in the training set, the genome-wide PS was associated with the depression score in the testing set (P = 0.004), Inhibitors,research,lifescience,medical but explained only 0.1% of the variance. The maximum percentage of variance explained was achieved with slightly more conservative P-value thresholds for SNP selection (at P < 0.3), in which the genome-wide PS explained 0.2% of the variance (P = 0.003). When restricted to nonoverlapping Ptraining threshold Inhibitors,research,lifescience,medical ranges, the SNPs with the most significant association were those with Ptraining

between 0.1 and 0.2; this group alone comprised nearly 9900 SNPs, but explained 0.1% of phenotype variation (Table 3). Table 3 Meta-analysis of percentage Inhibitors,research,lifescience,medical of variance explained in depression phenotype in NHS by the genome-wide agnostic polygenic scores in the leave-one-substudy-out analysis (N = 6989). GAIN-MDD-PS and PGC-MDD-PS analyses Regardless of the P-value threshold chosen, the GAIN-MDD-PS was not significantly associated Inhibitors,research,lifescience,medical with either the continuous or dichotomized depression phenotype in

the NHS sample (Table 4). The maximal proportion explained by genome-wide PS comparing women at the extremes of the phenotype was higher than that in the full sample (0.4% vs. 0.1%); however, it was not statistically significant, likely due to the reduction in sample size when using only individuals with extreme values of the phenotype (n = 2920) (data not shown). Table 4 Meta-analysis of percentage of variance explained in depression phenotype in NHS by the genetic risk scores using external GAIN-MDD sample as the training set (N = 6989). When applying the agnostic PS Inhibitors,research,lifescience,medical from a nine-study meta-analysis of PGC-MDD, the genome-wide risk scores derived from SNPs with less stringent Ptraining threshold were significantly associated with the continuous long-term depressive score, but they only explained at most 0.1% of variance in phenotype. The Nagelkerke’s R2 was also at most 0.1% when the depression phenotype was modeled dichotomously without over the statistical significance (Table 5). Table 5 Meta-analysis of percentage of variance explained in depression symptoms in NHS by the genetic risk scores using external PGC-MDD sample as the training set (N = 6989). Candidate-PS analyses Three individual SNPs (rs36011, rs1417584, and rs6917735) showed nominally significant associations at α threshold of 0.05, but none remained significant after Bonferroni correction.

We can thus extrapolate from this that vigilance

for threatening faces is not an exclusive function of selleck chemicals anxiety as previously reported (see review paper by Mogg and Bradley 2005). Once again, a possible explanation for why the present study found significance for threat stimuli in sad mood while others have found this primarily in anxious samples (e.g.,Van Honk et al. 2001; Mogg and Bradley 2002; Mogg et al. 2007) can perhaps be due to the exclusive use of verbal stimuli. Valenced verbal stimuli, although highly valuable for the study of attentional bias, may lack Inhibitors,research,lifescience,medical the potency necessary to elicit an externally driven attentional bias, namely for threatening angry faces. For instance, a survey of the referenced articles in the review paper by Mogg and Bradley (2005) reveals that with the exception of one study that utilized Inhibitors,research,lifescience,medical emotional face stimuli (Bradley et al. 1999), all other experiments utilized emotional words. If the suggestion about faces having more strength for threat detection

holds true, this could partially explain the lack of findings for an external threat bias in both sad mood and depressed samples. Second, although highly speculative at this point, it is not entirely convincing that threatening faces are Inhibitors,research,lifescience,medical strictly signals of danger in the environment and thus belong exclusively in the anxiety attentional bias camp. An angry face can possibly be a signal of impending doom and aggression for the anxious observer or a signal of disapproval and rejection for the

sad or depressed observer. Lastly, contrary to our hypothesis, happy mood participants did not pay more attention to positive stimuli. In the Inhibitors,research,lifescience,medical present study, these participants paid less attention to negative stimuli suggesting that perhaps the protective bias can also be defined by what healthy controls do not attend to, namely negative stimuli. Summary and Conclusions The present study investigated attentional interference for both emotional words and emotional faces across a wide range of valences. Overall, the present results Inhibitors,research,lifescience,medical support earlier studies indicating that people in a sad mood show slower reaction times to processing affective. A limitation of our study merits comment. To assess self-processing within an emotional context, Resminostat it has been recommended that valenced words be restricted to self-referencial stimuli (Fossati et al. 2003). The present study controlled for many aspects of the verbal stimuli (e.g., arousal, word length) but was not exclusively categorized by self-referential words. Overall, the present results support earlier studies indicating that people in a sad mood show slower reaction times to processing affective information (Leppanen 2006), particularly when the stimuli are negatively valenced (Baumeister et al. 2001). We have identified specific verbal and facial emotional cues that lead to interference in attention for those in a sad mood.

Figure 5c depicts phantom images obtained for the DPNs using a 3T MRI clinical scanner. All three nanoconstructs incorporate ultrasmall SPIOs with a 5 nm metallic core that is, eventually, degraded and metabolized by the cells without any significant Selleckchem MLN8237 toxicity. Figure 5 (A) Graphical configuration of a cluster of stem cells inject. (A) Graphical representation

of a 5-nm superparamagnetic iron oxide nanoparticle Inhibitors,research,lifescience,medical (SPIO); a 150-nm hybrid nanoparticle (HNP); discoidal 1,000 x 400 nm mesoporous silicon particle (SiMP); and … Note that in stem cell labeling, it is very important to have access to different nanotechnological platforms in that the nanoconstructs per se can affect the cell behavior.48 Importantly, these nanoconstructs can be remotely manipulated Inhibitors,research,lifescience,medical via static magnetic fields because of their

huge content in magnetic material (about 100 fg of iron per DPN) and can release directly inside the stem cell molecular agents for stimulating and controlling cell differentiation. Moreover, these nanoconstructs can be labeled with radionucleotides, thus merging together MRI and nuclear imaging, which could help in assessing cell functionality and viability in addition to cell tracking.49 Conclusions The efficiency of stem cell homing within the infarcted tissue can be predicted using patient-specific computational modeling as a function of Inhibitors,research,lifescience,medical the vascular geometry, blood flow conditions, and location of the infarcted area. Multifunctional magnetic nanoconstructs can serve to spatially and temporally track Inhibitors,research,lifescience,medical the injected stem cells and test for their viability. The combination

of computational modeling and sophisticated nanoconstructs for cell labeling should pave the way to new clinical trials for cell-based therapies in cardiovascular disease. Acknowledgements The author would like to thank Dr. T.R. Lee, Dr. J. Singh, Dr. S. Hossain, Inhibitors,research,lifescience,medical and Mr. M. Landry at Houston Methodist Hospital Research Institute for helping with the figures and data generation. The author acknowledges the collaboration with Dr. T.J.R. Hughes at The University of Texas, Austin, and with Dr. W.K. Liu at Northwestern University for the development of the computational module 1 and 2, respectively. The patient-specific data on PAD were kindly provided by Dr. D. Shah at the Houston Methodist DeBakey Heart Montelukast Sodium & Vascular Center and Dr. G. Bruner at Baylor College of Medicine. Funding Statement Funding/Support: The author has no funding disclosures. Footnotes Conflict of Interest Disclosure: The author has completed and submitted the Methodist DeBakey Cardiovascular Journal Conflict of Interest Statement and none were reported.
Introduction There is an increasing demand in regenerative medicine to repair and restore the function of injured, degenerated, or congenitally defected tissues. In a wide range of pathology, neither native nor purely artificial implantable materials can adequately replace or repair these damaged tissues.

First: that X-rays are electromagnetic waves with a wavelength of about 10−10 m, and second: that the internal structure of crystals is regular, and that it is arranged in three-dimensional structures. William Lawrence Bragg and his father, Sir William Henry Bragg,

developed an equation, aptly named Bragg’s law, which measures the NVP-BGJ398 manufacturer angles and spacing between the atoms of the crystal, thus allowing the crystalline structure to be constructed from the scattered dots seen on an X-ray diffraction pattern. Zinc sulphate was the first crystal studied by Inhibitors,research,lifescience,medical von Laue. This crystal was not only ordered but was periodic as well. Von Laue analyzed many other crystals and found that they all shared these two properties. For 70 years, from 1912 to 1982, hundreds of thousands of crystals were studied,

all of which were ordered and periodic. There were no exceptions. Inhibitors,research,lifescience,medical Due to this overwhelming empirical evidence, a paradigm was developed for the definition of a crystal. For example, a well-known textbook by B. D. Culity, Elements of X-Ray Diffraction (1959), defines a crystal as “a solid composed of atoms arranged Inhibitors,research,lifescience,medical in a periodic pattern in three dimensions.” This definition was not developed from a theoretical model but came from repeated observations. Charles Kittel writes in his influential textbook Introduction to Solid State Physics the following: “We can make a crystal from molecules which individually have a five-fold rotation axis, but we should not expect the lattice to have a five-fold Inhibitors,research,lifescience,medical rotation axis.” Crystals do not have to be made of atoms with repeating periodic patterns. Crystals can be made up of molecules, even very Inhibitors,research,lifescience,medical large molecules such as proteins, with repeating periodic patterns. The individual molecules of this crystal can have a five-fold rotational symmetry, but the crystal as a whole cannot have a five-fold rotational

symmetry. As an illustration, a connected array of pentagons cannot fill the entire plane without leaving gaps. Therefore, it was assumed that there are no crystals with a five-fold rotation axis and no crystals with more than a six-fold rotational axis. For example, a diamond (Figure 3) is an ordered and periodic crystal. The rotational symmetries that are allowed Amisulpride in this crystal are one, two, three, four, and six. It has no five-fold rotational axis and no rotational axis above six. Figure 3 Atoms in a diamond as seen under an electron microscope. THE DISCOVERY OF QUASI-PERIODIC CRYSTALS Science advances through discoveries. Most discoveries are incremental in nature, and although they broaden our horizons and are beneficial to mankind, they do not break any norms nor do they cause paradigm shifts. Occasionally, an interesting discovery comes along and causes a shake-up in the scientific community.