Canine pseudopregnancy: an evaluation of prevalence and current treatment protocols in the UK

Background: There is a dearth of literature on pseudopregnancy in the bitch, with only a few treatment-based studies published since the 1990s. Pseudopregnancy may be under-recognised in bitches and may account for a proportion of behavioural cases seen in veterinary practices including aggression. Little is known about commonly used treatments for overtly pseudopregnant bitches and it is possible that current regimes may not be prescribed for a sufficient duration to control any clinical signs including, physical and behavioural changes. To investigate current trends in diagnosis and treatment of canine pseudopregnancy, a postal survey was sent to 2000 randomly selected veterinary surgeons in UK veterinary practices. The questionnaire queried how often vets recognise cases of pseudopregnancy in spayed and entire bitches, which physical or behavioural signs are commonly recognised for diagnosis, and which management or treatment protocols are used. Results: The response rate was 19.8% (397/2000). Ninety-six percent of veterinary surgeons reported seeing pseudopregnant bitches showing behavioural changes without any physical changes within the last 12 months. Of those behavioural changes, collecting and mothering objects was the most frequently reported behavioural sign (96%). Ninety-seven percent of vets had seen aggression in pseudopregnant bitches. Nevertheless, only 52% of vets routinely asked owners about behavioural changes during consultations. Forty-nine percent of respondents reported seeing pseudopregnancy in spayed bitches. The most commonly reported physical sign was enlarged mammary glands and/or milk production (89%). Treatment options varied (surgical, medical or none) and depended on duration and severity of physical and behavioural signs, owners’ preference, cost, concurrent disease, drug availability and previous history. Conclusions: This is the largest epidemiological study of canine pseudopregnancy in the UK. The prevalence and severity of clinical signs in dogs with pseudopregnancy are variable and possibly under-estimated. Dogs with overt pseudopregnancy experience diverse physical and behavioural changes and information on standard treatment protocols are lacking. Although, progress on our understanding of diagnosis and treatment of pseudopregnancy in spayed and entire bitches has been made, further studies are warranted

Infrastructure shortfall in the United Kingdom: the private finance initiative and government policy

Investment infrastructure is essential for long term economic growth, sustainable regional economic development, and the quality of urban life. Yet the available evidence suggests a significant shortfall in current UK government investment on infrastructure, and a long term pattern of low investment compared to other European countries. Given the pre-occupation of the Labour government with managing expenditures within the parameters set by the previous government, and the vulnerability of any government to financial markets' valuation of current spending plans in relation to interest rates and currency exchange rates, there is little likelihood of major new public spending on infrastructure in the near future. In this context, the Private Finance Initiative (PFI) is very important for the government's plans to make up the shortfall. Although inherited from the previous Conservative government, the PFI has powerful advocates within the Labour government. The PFI is the formal mechanism by which government departments, agencies and instrumentalities, like the National Health Service, utilise private sector investment capital and, in particular, pension fund assets, to revitalise public services. This paper sets out the institutional history of the PFI, beginning with the Thatcher government's Ryrie Rules, the efforts of the Major Conservative government to make it a viable operational practice, and the reasons why the new government supports PFI and has made significant moves to improve its effectiveness. Still we are sceptical about the future of the PFI. We show that the PFI has foundered upon fundamentally flawed design and the politicians' obsession with control of public sector spending. Notwithstanding recent ‘reforms', PFI may only succeed if the PFI process is decentralised and linked explicitly with regional development programmes. In any event, given the difficulties posed by the PFI process for private investors, perhaps different institutional responses to infrastructure shortfall should be contemplated, including the introduction of traded infrastructure bonds

Inaccurate assessment of canine body condition score, bodyweight, and pet food labels: a potential cause of inaccurate feeding

The objectives were to investigate owners’ ability to assign the correct bodyweight (BW) and body condition score (BCS) to their dog and to interpret wet and dry pet food labels by estimating how much to feed daily. One hundred and seventy-four questionnaires were completed. Owner estimated BW was compared to actual BW, correct being defined within ±10% of actual BW. Correct interpretation of the total amount of food required was determined by the number of cans (±25% of cans) required for wet food and grams (±20% of grams) for dry food, based on the dog’s actual BW, the feeding guidelines on the label, and a comparison with the owner’s estimate. Eleven percent of owners overestimated BCS and 19% overestimated BW. Only 48% of owners could correctly estimate their dog’s BW. Only 23% and 43% of owners could correctly estimate how much wet and dry food to feed, respectively. Chi-square analysis demonstrated a significant positive association for owners correctly estimating their dog’s BW and interpreting the wet pet food label. Many owners are not aware of their pet’s BCS and BW and cannot accurately interpret pet food labels. Further owner education to improve these skills is needed if dogs are to be fed correctly

Targetable vulnerabilities in T- and NK-cell lymphomas identified through preclinical models

T- and NK-cell lymphomas (TCL) are a heterogenous group of lymphoid malignancies with poor prognosis. In contrast to B-cell and myeloid malignancies, there are few preclinical models of TCLs, which has hampered the development of effective therapeutics. Here we establish and characterize preclinical models of TCL. We identify multiple vulnerabilities that are targetable with currently available agents (e.g., inhibitors of JAK2 or IKZF1) and demonstrate proof-of-principle for biomarker-driven therapies using patient-derived xenografts (PDXs). We show that MDM2 and MDMX are targetable vulnerabilities within TP53-wild-type TCLs. ALRN-6924, a stapled peptide that blocks interactions between p53 and both MDM2 and MDMX has potent in vitro activity and superior in vivo activity across 8 different PDX models compared to the standard-of-care agent romidepsin. ALRN-6924 induced a complete remission in a patient with TP53-wild-type angioimmunoblastic T-cell lymphoma, demonstrating the potential for rapid translation of discoveries from subtype-specific preclinical models